HK1243304B - System and method to increase the overall diameter of veins and arteries - Google Patents

Description

Systems and methods for increasing the overall diameter of veins and arteries

This invention patent application is a divisional application of the invention patent application with international application number PCT/US2012/050978, international application date August 15, 2012, application number 201280050718.0 entering the Chinese national phase, and name “System and method for increasing the total diameter of veins and arteries”.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Patent Application No. 61/561,859, filed on November 19, 2011, entitled “System and Method to Increase the Overall Diameter of Veins and Arteries,” and claims priority to U.S. Patent Application No. 61/524,759, filed on August 17, 2011, entitled “System and Method to Increase the Overall Diameter of Veins and Arteries,” which is a continuation-in-part of U.S. Patent Application No. 13/030,054, filed on February 17, 2011, entitled “System and Method to Increase the Overall Diameter of Veins,” which claims priority to U.S. Patent Application No. 13/030,054, filed on February 17, 2010, entitled “System and Method to Increase the Overall Diameter of Veins and Methods,” and is related to co-pending U.S. Patent Application No. 61/524,761, entitled “Blood Pump Systems and Methods,” and U.S. Patent Application No. 61/564,671, entitled “Blood Pump Systems and Methods,” all of which are incorporated herein by reference in their entireties.

Technical Field

The present invention relates to systems and methods for continuously increasing the total diameter and lumen diameter of veins and arteries in the human body. Specifically, the present invention relates to systems and methods for using a blood pump to increase blood velocity and wall shear stress (WSS) on the endothelium of peripheral veins and arteries to cause a sustained increase in the total diameter and lumen diameter of these veins and arteries over a sufficient period of time.

Background Art

Many patients suffering from chronic kidney disease (CKD) eventually develop into end-stage renal disease (ESRD) and need renal replacement therapy, to remove fluid and waste from their body and maintain their life. Most patients suffering from ESRD and need renal replacement therapy receive hemodialysis, in which blood is removed from the circulatory system, cleaned in a hemodialysis machine, and then returned to the circulatory system. In order to facilitate hemodialysis, surgeons form discrete "vascular access sites" that can be used to quickly remove and return blood from ESRD patients. Although hemodialysis machines themselves and other components of the hemodialysis process have obtained significant progress, the formation of durable and reliable vascular access sites has only seen little improvement and remains the Achilles' heel of renal replacement therapy. Failure to provide suitable vascular sites often results in ESRD patients becoming ill and dying, and has brought a heavy burden to worldwide health care providers, payers, and official aid programs.

Vascular access sites for hemodialysis typically come in three forms: arteriovenous fistulas (AVFs), arteriovenous grafts (AVGs), and catheters. Each access site is subject to a high rate of failure and complications, as described below.

An AVF is surgically constructed by forming a direct connection between an artery and a vein. A functional AVF formed between the radial artery and the brachial vein at the wrist is the most durable and ideal form of hemodialysis access, with an average patency of approximately three years. The vein exiting this connection is called the "outflow" vein. The continued increase in the total and luminal diameter of the outflow vein is a key component of an AVF's maturation and usability. It is widely believed that the rapid flow of blood through the outflow vein formed by the AVF and the WSS imposed on the venous endothelium are the primary factors contributing to the continued increase in the total and luminal diameters of the outflow vein. Unfortunately, approximately 80% of ESRD patients are not suitable for AVF placement in the wrist due to insufficient venous or arterial diameter. Of eligible patients who undergo AVF placement, approximately 50%-60% fail to utilize the site without further intervention, a problem known as "patency failure." Small vessel diameter, particularly small venous diameter, has been recognized as a contributing factor to AVF patency failure. The rapid onset of invasive venous wall scarring, known as "intimal hyperplasia," has also been implicated as a significant factor in AVF patency failure. Some researchers hypothesize that regions of relatively rapid or turbulent blood flow within the vein (with resulting high local WSS) are the primary factor contributing to venous wall scarring, while others propose that this scarring is caused by regions of relatively slow or oscillatory blood flow and relatively low or oscillatory WSS. In response, attempts have been made to modulate the flow pattern in the AVF outflow vein to minimize the rate of AVF failure. Still others hypothesize that the cyclical stretching of the vein caused by the influx of pulsatile arterial blood also plays a role in stimulating intimal hyperplasia and obstructing the outflow vein within the AVF. Currently, there is no method for maintaining the positive effects of elevated blood velocity and WSS, which lead to a sustained increase in the overall and luminal diameters of arteries and veins, while also eliminating the negative effects of venous wall scarring and obstruction. Not surprisingly, patients newly diagnosed with ESRD requiring hemodialysis have only a 50% chance of having a functioning AVF within 6 months of starting hemodialysis. Those without a functioning AVF must rely on more costly forms of vascular access for hemodialysis and are at greater risk of complications, morbidity, and mortality.

The second type of vascular access site for hemodialysis is the arteriovenous graft (AVG). An AVG is constructed by placing a length of synthetic tubing between an artery and a vein. Typically, an AVG is constructed in an arm or leg. A portion of the synthetic tubing is placed just below the skin and serves as a needle access. More patients are suitable for AVGs than AVFs because veins that are not visible on the skin surface can be used for outflow, and the early failure rate is much lower than that of AVFs. Unfortunately, the average primary patency of an AVG is only about 4-6 months, because invasive intimal hyperplasia and scarring rapidly develop in the wall of the outflow vein near the connection with the synthetic tubing, leading to stenosis and thrombosis. Similar to AVF failure, some researchers hypothesize that the rapid turbulence of blood in the outflow vein formed by the AVG causes intimal hyperplasia and scarring in the wall of the outflow vein, while other researchers hypothesize that this scarring is caused by areas with relatively slow or oscillatory blood flow and relatively low or oscillatory WSS. Other researchers have hypothesized that cyclical stretching of the veins caused by the influx of pulsatile arterial blood into the outflow veins also plays a role in the development of intimal hyperplasia and outflow vein obstruction within AVFs. Although AVGs are less desirable than AVFs, approximately 25% of patients undergo dialysis with AVGs, primarily because they are not suitable candidates for AVFs.

The third type of vascular access site is a catheter. Patients who cannot obtain hemodialysis through an AVF or AVG can have a large catheter inserted into the neck, chest, or leg to receive hemodialysis. These catheters often become infected, putting patients at high risk of sepsis and death. Patients with catheter sepsis usually need to be hospitalized, have the catheter removed, have a temporary catheter inserted, be treated with intravenous antibiotics, and then have a new catheter or other type of access site placed when the infection has cleared. Catheters can also be prone to thrombotic obstruction and fibrin accumulation around the ends. Hemodialysis catheters have an average patency of about 6 months and are generally the least ideal form of hemodialysis access. Although catheters are more undesirable than AVFs and AVGs, approximately 20% of patients undergo dialysis with a catheter, primarily because they cannot or are not suitable for receiving a functional AVF or AVG.

The problem of hemodialysis access site failure has received increasing attention recently, and this is because the number of ESRD patients undergoing conventional hemodialysis is increasing worldwide. In 2004, the Centers for Medicare and Medicaid Services (CMS) announced the "Fistula First" initiative, so as to increase the use of AVF in providing hemodialysis access for patients with end-stage renal failure. This major initiative is a response to published medical insurance data, which show that patients dialyzed with AVF have reduced morbidity and mortality compared to patients with AVG or catheters. In the first year of dialysis and subsequent years, the cost associated with AVF patients is significantly lower than the cost associated with AVG patients. When compared with dialyzing with a catheter, the cost savings of dialyzing with AVF are even greater.

To be eligible for an AVF, a patient typically needs to have a peripheral vein with a total diameter of at least 2.5 mm or a peripheral artery with a total diameter of at least 2.0 mm, although it should be understood that different vascular surgeons may set different threshold levels. To be eligible for an AVG, a patient typically needs to have a peripheral vein with a total diameter of at least 4 mm and a peripheral artery with a total diameter of at least 3.0 mm, although it should be understood that different vascular surgeons may set different threshold levels. Currently, there are no methods for consistently increasing the total and lumen diameters of peripheral veins and arteries in ESRD patients who do not have adequate initial vein or artery size prior to AVF or AVG creation. Therefore, patients whose veins or arteries are too small to attempt an AVF or AVG must use less-than-ideal forms of vascular access, such as catheters. Similarly, there are currently no approved methods for treating AVF patency failure, which disproportionately occurs in patients with small veins and arteries, such as women and minors. Therefore, there is a need for systems and methods for increasing the total and lumen diameters of veins or arteries prior to AVF or AVG creation. A recent study demonstrates that patients with end-stage renal disease (ESRD) who are forced to use less-than-ideal forms of vascular access, such as catheters, have a significantly higher risk of morbidity or mortality compared with those who are able to undergo hemodialysis using an AVF or AVG.

For patients who require bypass grafts due to atherosclerotic blockages of peripheral or coronary arteries, there is also a need to continuously increase the diameter of the veins or arteries. Patients with peripheral arterial disease (PAD) who have blood flow blockages in their leg arteries often suffer from claudication, skin ulcers, and localized tissue ischemia. Many of these patients may eventually need to have part of their affected limb amputated. In some PAD patients, the blockage can be alleviated to a sufficient degree by balloon angioplasty or the implantation of a vascular stent. However, in other patients, the blockage is too severe for these types of minimally invasive therapies. Therefore, surgeons typically create a bypass graft that bypasses the blood around the blocked artery and restores adequate blood flow to the affected limb. However, many patients who need peripheral bypass grafts are unable to use their own veins as bypass conduits due to insufficient vein or artery diameter and are forced to use synthetic conduits made of materials such as expanded polytetrafluoroethylene (ePTFE, such as Gore-Tex) or polyethylene terephthalate (PET, such as Dacron). Studies have shown that using a patient's own vein as a bypass conduit can result in longer patency than using synthetic bypass conduits made of materials such as PTFE, ePTFE, or Dacron. The use of synthetic bypass conduits increases the risk of stenosis in the artery distal to the graft and thrombosis throughout the conduit, leading to bypass graft failure and recurrence or worsening of symptoms. Therefore, for patients who are not suitable for using their own vein to create a bypass graft due to insufficient vein diameter, there is a need for systems and methods for increasing the overall diameter and lumen diameter of the vein prior to creating a bypass graft.

Patients with coronary artery disease (CAD), whose blood flow to the heart is impaired, often suffer from chest pain, myocardial ischemia, and myocardial infarction, and many of these patients ultimately die from the disease. In some of these patients, the blockage can be alleviated to a sufficient degree by balloon angioplasty or the implantation of a vascular stent. However, in many patients, the blockage is too severe for these types of minimally invasive therapies. Therefore, surgeons typically create a bypass graft that diverts blood around the blocked artery and restores adequate blood flow to the affected area of the heart, with the internal mammary artery and radial artery being preferred conduits. However, some patients who require a coronary artery bypass graft cannot use the internal mammary artery or radial artery due to insufficient artery diameter and must use a peripheral vein. Studies have shown that using a patient's internal mammary artery and radial artery as a bypass conduit can produce a longer patency period than using a peripheral vein segment. Using a peripheral vein as a bypass graft increases the risk of stenosis in the graft and thrombosis of the entire conduit, leading to bypass graft failure and recurrence or worsening of symptoms. Therefore, for patients who are not suitable for using their own arteries to create a bypass graft due to insufficient arterial diameter, there is a need for systems and methods for increasing the overall diameter and lumen diameter of the arteries prior to creating a coronary artery bypass graft. Furthermore, for patients with smaller peripheral vein diameters, there is also a need for systems and methods for increasing the overall diameter and lumen diameter of the veins prior to creating a coronary artery bypass graft.

Summary of the Invention

The present invention includes methods for increasing the total diameter and lumen diameter of peripheral veins and arteries using a blood pump. Systems and methods are described in which the average wall shear stress or peak wall shear stress applied to the endothelium of a peripheral vein or artery is increased by pumping blood into the peripheral vein or artery at a sufficient rate and for a period sufficient to result in a sustained increase in the total diameter and lumen diameter of the peripheral vein or artery. The pump discharges blood into the peripheral vein or artery, preferably in a manner such that the blood has a reduced pulse pressure when compared to the pulse pressure of the blood in the peripheral artery. Systems and methods are also described in which the wall shear stress (WSS) applied to the endothelium of a peripheral vein or artery is increased by pumping blood out of the peripheral vein or artery at a sufficient rate and to another location in the vascular system, such as the right atrium, for a period sufficient to result in a sustained increase in the total diameter and lumen diameter of the peripheral vein or artery.

Studies have shown that changes in baseline hemodynamic force and hemodynamic force in veins and arteries play a key role in determining the total diameter and lumen diameter of these veins and arteries. For example, the continuous increase of blood velocity and WSS can lead to a continuous increase in the total diameter and lumen diameter of veins and arteries, wherein the amount of increase in total diameter and lumen diameter depends on the level of increased blood velocity and WSS and the time over which blood velocity and WSS rise. Elevated blood velocity and WSS are sensed by endothelial cells, which trigger a signaling mechanism that stimulates vascular smooth muscle cells, attracts monocytes and macrophages, and synthesizes and releases proteases that can degrade components of the extracellular matrix such as collagen and elastin. Therefore, the present invention relates to increasing blood velocity and WSS over a period sufficient to cause vascular reconstruction and a continuous increase in the total diameter and lumen diameter of veins and arteries, preferably over a period greater than 7 days. The present invention also relates to a method for regularly manually or automatically adjusting pump parameters to optimize the blood velocity and WSS in the target artery or vein, and to optimize the rate and degree of continuous increase in the total diameter and lumen diameter of veins and arteries.

Wall shear stress has been shown to be a key factor in the continuous increase in total and lumen diameter of veins and arteries in response to increased blood flow. Assuming Hagen-Poiseuille flow in a vessel (i.e., laminar flow with a fully developed parabolic velocity profile), WSS is given by:

WSS(Pa)＝4Qμ/πR ³ , where:

Q = flow rate (m ³ /s)

μ＝blood viscosity (Pa/s)

R = Radius of blood vessel (m)

The systems and methods described herein increase the WSS levels in peripheral veins and arteries. The normal average WSS of the vein is in the range of 0.076Pa and 0.76Pa. In order to permanently increase the total diameter and lumen diameter of the vein, the systems and methods described herein increase the average WSS levels to a range between 0.76Pa and 23Pa, preferably to a range between 2.5Pa and 10Pa. The normal average WSS of the artery is in the range of 0.3Pa and 1.5Pa. In order to permanently increase the total diameter and lumen diameter of the artery, the systems and methods described herein increase the average WSS levels to a range between 1.5Pa and 23Pa, preferably to a range between 2.5Pa and 10Pa. Preferably, the average WSS increase reaches a time period between 1 day and 84 days (or longer), to cause a continuous increase in the total diameter and lumen diameter of peripheral veins and arteries that are initially unqualified or non-optimal for use as hemodialysis access sites or bypass grafts due to small vein or artery diameters, making them usable or better. This can also be achieved by intermittently increasing mean WSS during treatment with intervening periods of normal mean WSS.

The systems and methods described herein also increase the velocity and/or speed of blood in peripheral veins and arteries. At rest, the average velocity of blood in the cephalic vein of a human body generally varies between 5 and 9 cm/s (0.05 and 0.09 m/s). For the systems and methods described herein, the average velocity of blood in the peripheral veins is increased to a range between 10 cm/s and 120 cm/s (0.1 and 1.2 m/s), preferably to a range between 25 cm/s and 100 cm/s (0.25 m/s and 1.0 m/s), depending on the initial diameter of the vein, the desired post-treatment diameter of the vein, and the planned length of treatment (with elevated WSS).

At rest, the average velocity of blood in the brachial artery generally varies between 10 and 15 cm/s (0.1 and 0.15 m/s). For the systems and methods described herein, the average velocity of blood in the peripheral arteries is increased to a range between 10 cm/s and 120 cm/s (0.1 and 1.2 m/s), and preferably to a range between 25 cm/s and 100 cm/s (0.25 m/s and 1.0 m/s), depending on the initial diameter of the artery, the desired post-treatment diameter of the artery, and the planned length of treatment (by increasing WSS).

Preferably, the mean blood velocity is increased for a period of between 1 day and 84 days (or longer), or preferably for a period of between 7 and 42 days, to cause a sustained increase in the overall diameter and lumen diameter of peripheral veins and arteries, such that veins and arteries that were initially unqualified or suboptimal for use as hemodialysis access sites or bypass grafts due to small vessel diameters become usable or more optimal. This can also be achieved by intermittently increasing the mean blood velocity during treatment with intervening periods of normal mean blood velocity.

This article describes a method for increasing the lumen diameter and total diameter of a peripheral vein or artery in a patient. The method includes performing a first procedure to access an artery, vein, or right atrium (donor vessel) and a peripheral vein or artery (recipient vessel), and utilizing a pump system to "fluidically connect" the donor vessel (i.e., lumen-to-lumen engagement of the two vessels to allow fluid communication therebetween) to the recipient vessel. The pump system is then activated to actively move blood from the donor vessel to the recipient vessel. The method also includes monitoring the progress of blood pumping over a period of time. The method further includes adjusting the pump speed, the velocity of the blood, and/or the rate at which blood is pumped in a desired specific direction or vector of blood flow (e.g., in an antegrade or retrograde direction), the mean or peak WSS across the endothelium of the recipient vessel, and again monitoring the progress of the pumping. After a period of time has elapsed to allow for a sustained increase in the total and lumen diameters of the recipient vessel, the diameter of the recipient vessel is measured to determine whether a sufficient sustained increase in the total and lumen diameters of the recipient vessel has been achieved. The blood velocity and/or rate and WSS are measured, and the pumping process is adjusted again if necessary. When a sufficient amount of sustained increase in the overall and lumen diameters of the recipient vessel is achieved, a second procedure is performed to remove the pump. A hemodialysis access site (e.g., AVF or AVG) or bypass graft can be formed using at least a portion of the continuously enlarged recipient vessel at the time of or after pump removal.

This article also describes a method for increasing the lumen diameter and total diameter of a peripheral vein or artery in a patient. The method includes: fluidically connecting a peripheral artery or vein (donor vessel) to another location in the venous system (a recipient location) using a blood pump system; and then activating the blood pump system to actively move blood from the donor vessel to the recipient location, optionally using one or more blood conduits. The method also includes monitoring the blood pumping process over a period of time. The method further includes adjusting the pump speed, the rate at which blood is pumped, or the average or peak WSS on the endothelium of the donor vessel, and again monitoring the pumping process. After a period of time has elapsed to result in a sustained increase in the total and lumen diameters of the donor vessel, the diameter of the donor vessel is measured to determine whether a sufficient sustained increase in the total and lumen diameters of the donor vessel has been achieved, the blood speed and WSS are measured, and the pumping process is adjusted again if necessary. When a sufficient sustained increase in the total and lumen diameters of the donor vessel has been achieved, a second procedure is performed to remove the pump. A hemodialysis access site (eg, AVF or AVG) or bypass graft can be formed using at least a portion of the continuously enlarged donor vessel at the time of pump removal or at a later time.

In one embodiment, a surgical procedure is performed to expose two segments of veins. One end of a first synthetic conduit is fluidically connected to the vein from which blood will be removed (the donor vein). The other end of the first synthetic conduit is fluidically connected to the inflow port of a pump. One end of a second synthetic conduit is fluidically connected to the vein into which blood will be transferred (the recipient vein). The other end of the second synthetic conduit is fluidically connected to the outflow port of the same pump. Deoxygenated blood is pumped from the donor vein to the recipient vein until the total diameter and lumen diameter of the recipient vein continuously increase to the desired amount. When used to describe the expansion or increase in the total diameter and lumen diameter of an artery or vein, the term "sustained increase" or "sustained expansion" is used herein to mean that even if the pump is turned off, an increase in the total diameter or lumen diameter of the vessel can still be demonstrated compared to the total diameter or lumen diameter of the vessel before the blood pumping period. In other words, the total diameter or lumen diameter of the vessel has increased, regardless of the pressure generated by the pump. Once the desired amount of continuous increase in the total diameter and lumen diameter of the recipient vein occurs, a second surgical procedure is performed to remove the pump and synthetic conduit. A hemodialysis access site (e.g., an AVF or AVG) or a bypass graft can be formed using at least a portion of the continuously enlarged recipient vein at the time of or after the pump is removed. In this embodiment, the pump port can be directly fluidically connected to the donor vein or the recipient vein without the use of an intervening synthetic conduit. In a variation of this embodiment, the recipient vein can be located in one body location, such as the cephalic vein in the arm, while the donor vein can be in another location, such as the femoral vein in the leg. In this case, both ends of the pump-tubing assembly will be located within the body, and the bridging portion of the pump-tubing assembly can be extracorporeal (outside the body, e.g., worn under clothing) or implanted (e.g., tunneled in subcutaneous tissue). Moreover, in some cases, the donor vessel can be located more peripherally than the recipient vein in an opposing body location.

In another embodiment, a method includes a surgical procedure that exposes a segment of a peripheral artery and a segment of a peripheral vein. One end of a first synthetic tubing is fluidically connected to the peripheral artery. The other end of the first synthetic tubing is fluidically connected to an inflow port of a pump. One end of a second synthetic tubing is fluidically connected to the peripheral vein. The other end of the second synthetic tubing is fluidically connected to an outflow port of the same pump. Oxygenated blood is pumped from the peripheral artery to the peripheral vein until the total diameter and lumen diameter of the vein or artery continuously increase to a desired level. Once the desired amount of continuous increase in the total diameter and lumen diameter of the vein or artery occurs, a second surgical procedure is performed to remove the pump and synthetic tubing. A hemodialysis access site (e.g., an AVF or AVG) or a bypass graft can be formed using at least a portion of the continuously enlarged recipient vein or donor artery, or both, at the time of or after the pump is removed. A variation of this embodiment is provided in which the pump port can be directly fluidically connected to the artery or vein without the use of an intervening synthetic tubing.

In another embodiment, a method includes the following surgical procedure: performing the surgical procedure to expose a segment of a peripheral vein. One end of a first synthetic tubing is fluidically connected to the peripheral vein (donor vessel), while the other end of the first synthetic tubing is fluidically connected to the inflow port of a pump. One end of a second synthetic tubing is fluidically connected to the superior vena cava (recipient site), while the other end of the second synthetic tubing is fluidically connected to the outflow port of the same pump. Pumping of deoxygenated blood from the donor peripheral vein into the superior vena cava is performed until the total diameter and lumen diameter of the donor peripheral vein continuously increase to a desired level. Once the desired amount of continuous increase in total diameter and lumen diameter occurs in the donor peripheral vein, a second surgical procedure is performed to remove the pump and synthetic tubing. A hemodialysis access site (e.g., an AVF or AVG) or a bypass graft can be formed using at least a portion of the continuously enlarged peripheral donor vein at the time of or after the pump is removed. A variation of this embodiment is provided in which at least one venous valve is rendered incompetent between 1) the connection between the first synthetic tubing and the peripheral donor vein and 2) the right atrium to allow retrograde flow into the peripheral donor vein.

In another embodiment, a method includes the following surgical procedure: the surgical procedure is performed to expose a segment of a peripheral artery. One end of a first synthetic conduit is fluidly connected to the peripheral artery (donor vessel), and the other end of the first synthetic conduit is fluidly connected to the inflow port of a pump. One end of a second synthetic conduit is fluidly connected to the superior vena cava (recipient site), and the other end of the second synthetic conduit is fluidly connected to the outflow port of the same pump. Pumping of oxygenated blood from the peripheral artery to the superior vena cava is performed until the total diameter and lumen diameter of the peripheral donor artery continue to increase to a desired level. Once a desired amount of continuous increase in the total diameter and lumen diameter of the peripheral donor artery occurs, a second surgical procedure is performed to remove the pump and synthetic conduit. A hemodialysis access site (e.g., AVF or AVG) or a bypass graft can be formed using at least a portion of the continuously enlarged peripheral donor artery at the time of or after the pump is removed. A variation of this embodiment is provided in which synthetic tubing is used to directly fluidically connect a donor vessel (e.g., a peripheral artery) and a recipient site (e.g., the superior vena cava or right atrium), wherein blood flows passively from the high-pressure donor artery to the low-pressure recipient site without the use of a pump. In this embodiment, the increased blood velocity and WSS in the donor artery are caused by the arteriovenous confluence of blood from the high-pressure donor artery to the low-pressure recipient site, and when maintained for a sufficient amount of time, result in a continuous increase in the total diameter and lumen diameter of the donor artery. This embodiment is distinct from existing peripheral artery to right atrium grafts for hemodialysis because the system and method are configured to cause a continuous increase in the total diameter and lumen diameter of the donor artery, and are not configured for conventional needle puncture or conventional vascular access for hemodialysis. For example, the synthetic tubing in this embodiment has a shorter section of synthetic material such as PTFE, ePTFE, or Dacron that allows for anastomosis to a peripheral artery but is not usable or optimal for conventional needle puncture to obtain vascular access for hemodialysis.

In another embodiment, a pair of dedicated catheters are inserted into the venous system. The first end of a catheter (hereinafter referred to as "inflow conduit") is attached to the inflow port of the pump, and the first end of another catheter (hereinafter referred to as "outflow conduit") is attached to the outflow port of the pump. Alternatively, a part of these two catheters can be joined together to form a double lumen catheter. In one embodiment, each pipeline has a separate length between 2cm and 110cm and a combined length between 4cm and 220cm, and can be trimmed to the desired length by a surgeon or other physician, including during the implantation of the pump system. The pipeline each has an internal diameter between 2mm and 10mm and preferably 4mm. The pipeline can be at least partially formed by polyurethane (for example, or), polyvinyl chloride, polyethylene, silicone elastomer, polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyethylene terephthalate (PET, such as dacron) and a combination thereof. The catheter is constructed to be inserted into the lumen of the venous system. After insertion, the top of the second end of the inflow conduit is positioned at any position in the venous system where a sufficient amount of blood can be drawn into the inflow catheter (a "donor site," such as the right atrium, superior vena cava, subclavian vein, or brachiocephalic vein). After insertion, the top of the second end of the outflow conduit is positioned in a section of a peripheral vein (a "recipient vein") where blood can be transported by the outflow conduit (e.g., the cephalic vein near the wrist or the basilic vein near the elbow). The pump then draws deoxygenated blood from the donor site into the lumen of the inflow conduit and discharges the blood from the outflow conduit into the lumen of the recipient vein. In this embodiment, the pump and a portion of the inflow and outflow conduits can remain outside the patient's body. The pump is operated until a continuous increase in the desired amount of total diameter and lumen diameter occurs in the recipient vein, at which point the pump and conduit are removed. A hemodialysis access site (e.g., AVF or AVG) or a bypass graft can be formed using at least a portion of the continuously enlarged recipient vein at or after the time the pump is removed.

A system for increasing blood velocity, mean WSS, and/or peak WSS in a vein by delivering deoxygenated blood from a donor vein or right atrium to a recipient vein in a patient is provided. The system comprises two synthetic tubings (each having two ends), a blood pump, a control unit, and a power supply. The system may also include one or more sensor units. In one embodiment of the system, the synthetic tubing and pump, collectively referred to as a "pump-tubing assembly," are configured to remove deoxygenated blood from a donor vein or right atrium and pump the blood into a peripheral recipient vein. The pump-tubing assembly is configured to pump deoxygenated blood. In another embodiment of the system, the pump-tubing assembly is configured to remove oxygenated blood from a peripheral donor artery and pump the blood into a peripheral recipient vein. Blood is pumped in such a manner that the blood velocity in both the artery and vein increases and the WSS imposed on the endothelium of the artery and vein increases to a level and for a period of time sufficient to cause a sustained increase in the total diameter and lumen diameter of the peripheral arteries and veins. Preferably, the blood pumped into the peripheral vein has a low pulsatility, eg, a lower pulsatility than the blood in the peripheral artery.Variations of this embodiment are provided in which the pump is fluidly connected directly to the artery or vein (or both) without the use of intervening synthetic tubing.

The pump comprises an inlet and an outlet. The pump is constructed to increase the speed of the blood in the vein and to increase the mode of the WSS on the endothelium of the vein and hypoxia or oxygenated blood is delivered to the peripheral vein, to cause the overall diameter of peripheral recipient vein, peripheral donor artery or peripheral donor vein and the continuous increase of lumen diameter, specifically depending on the mode that specific embodiment and blood pump system are connected to vascular system and operation. The blood pump can be implanted in the patient's body, can remain on the patient's body, or can have an implantation portion and an external portion. All or some in the synthetic conduit can be implanted in the patient's body, can be implanted subcutaneously or can be implanted in the lumen of vein or arterial system or their any combination. The implantation portion of the pump-pipeline assembly can be regularly monitored and adjusted, for example, per second, per minute, per hour, every day, or every few days.

The present invention includes methods for increasing the blood velocity in a peripheral vein or peripheral artery and increasing the WSS imposed on the endothelium of a patient's peripheral vein or peripheral artery who requires a hemodialysis access site or bypass graft or other vascular surgery or clinical conditions where a larger peripheral artery or vein would be beneficial. A device designed to increase arterial blood flow for the treatment of heart failure would be useful for this purpose. In addition, any pump that can increase blood velocity and increase the WSS imposed on the recipient vessel can be used. In certain embodiments, a vascular assist device (VAD) optimized for low blood flow will be able to pump blood from a donor artery or vein to a peripheral vein to cause a sustained increase in the total diameter and lumen diameter of a peripheral recipient vein, and can be repurposed to increase the blood velocity and WSS in the peripheral recipient vein to a level and for a time sufficient to cause a sustained increase in the total diameter and lumen diameter of these peripheral arteries and veins. In other embodiments, a VAD capable of producing low blood flow will be able to pump blood from a donor vessel (artery or vein) to a recipient location and can be repurposed to increase the blood velocity and WSS in peripheral donor arteries and peripheral donor veins to a level and for a time sufficient to result in a sustained increase in the total diameter and lumen diameter of these peripheral arteries and veins. In one embodiment, a pediatric VAD such as a PediPump can be used. In another embodiment, a micro-VAD designed for treating moderate heart failure in adults (e.g., a Synergy pump provided by Circulite) can be used. Other devices can also be used, including left ventricular assist devices (LVADs) or right ventricular assist devices (RVADs) capable of achieving low blood flow. In other embodiments, an adjustable centrifugal or rotary blood pump (whose operation can be adjusted in real time) can be used to draw blood from a donor vessel and pump the blood to a recipient vessel.

The method includes: fluidly connecting a low-flow VAD, its derivatives, or a similar type of device to a donor vessel; removing blood from the donor vessel; and pumping the blood into a peripheral recipient vein at a sufficient flow rate and for a sufficient duration to cause a continuous increase in the total diameter and lumen diameter of the peripheral vein. The method also includes: fluidly connecting a low-flow VAD, its derivatives, or a similar type of device to a donor vessel (artery or vein); removing blood from the donor vessel; and pumping the blood into a recipient site at a sufficient flow rate and for a sufficient duration to cause a continuous increase in the total diameter and lumen diameter of the donor vessel. The blood pump can be implanted in the patient, or it can remain external to the patient. When the pump is external to the patient, it can be secured to the patient for continuous pumping. Alternatively, the pump can be configured to be removed from the patient's donor and recipient vessels for periodic and/or intermittent pumping phases.

While blood is being pumped, the lumen diameter of the peripheral recipient vein, peripheral donor artery, and peripheral donor vein can be monitored using conventional methods, such as ultrasound visualization, diagnostic angiography, or magnetic resonance imaging, or other methods. The pump-tubing assembly or pump-catheter assembly can incorporate features that facilitate diagnostic angiography, such as radiopaque markers that indicate a site accessible by needle or syringe for injection of contrast agent into the assembly, which will then flow into the recipient's peripheral veins to visualize the recipient's peripheral veins using conventional and digital subtraction angiography during fluoroscopy. Similarly, the blood pump system can incorporate features that facilitate ultrasound or MRI, such as making the blood pump system MRI-compatible. In other embodiments, the blood pump system can incorporate a control system having one or more sensors in communication with the blood pump or tubing to measure at least one of blood velocity, blood flow, resistance to blood flow into the peripheral vessels, blood pressure, pulsatility index, and combinations thereof. As used herein, "pulsatility" and "pulsatility index" refer to a measure of the fluctuation of blood velocity in a vessel, which is equal to the difference between the peak systolic velocity and the minimum diastolic velocity divided by the average velocity during the cardiac cycle.

When a portion of a pump-tubing assembly or pump-catheter assembly is located outside the body, an antimicrobial coating can be incorporated on the outer surface of at least a portion of a device comprising tubing, catheters, pumps, leads, or any combination thereof, particularly the portion connecting an implanted component to an external component. For example, when a controller and/or power supply is strapped to an arm or wrist, attached to a harness, or carried in a bag or backpack, an antimicrobial coating can be incorporated on the surface of materials that enter the patient's body, such as synthetic tubing, catheters, or pump leads. In another embodiment, a sheath can be applied to the portion of the device connecting the implanted component to the external component. The sheath can reduce the risk of infection by facilitating tissue bonding and can reduce the incidence of wounds by reducing the mobility of the connection point. In another embodiment, a coating that reduces thrombus accumulation (e.g., an antithrombotic coating) can be incorporated into the internal blood-contacting surfaces of the pump-tubing assembly and pump-catheter assembly. The antithrombotic coating can be incorporated into tubing, catheters, pumps, or any combination thereof. In other embodiments, a coating that increases lubricity can be added to, for example, tubing or leads to reduce friction during insertion or subcutaneous tunneling and facilitate the insertion or subcutaneous tunneling process.

In various embodiments, the present invention includes systems and methods for increasing the total diameter of a patient's peripheral arteries by removing oxygenated blood from the peripheral arteries and pumping the oxygenated blood into the right atrium at a rate and duration sufficient to cause a sustained increase in the total diameter of the peripheral arteries. Blood can be moved from the peripheral arteries to the right atrium with or without the use of a pump. Similarly, in another embodiment, the present invention includes systems and methods for increasing the total diameter of a patient's peripheral veins by removing deoxygenated blood from the peripheral veins and pumping the deoxygenated blood into the right atrium at a rate and duration sufficient to cause a sustained increase in the total diameter of the peripheral veins.

Arteries and veins that are subjected to a continuous increase in blood velocity and WSS can increase their total diameter and lumen diameter, and can also increase their total length. When arteries and veins have branches that are fixed to a certain extent, they respond to the increase in total length by increasing the tortuosity between the areas where the branch points are fixed. In certain clinical situations, an increase in blood vessel length may be desirable and therefore becomes the primary motivation for implanting, constructing, and operating an embodiment of a pump-tubing assembly. In this embodiment, the blood vessel can be removed after experiencing an increase in length and used in another position (e.g., for forming a bypass graft in a situation where a shorter segment is not optimal) or the blood vessel is detached from the fixation with the branch point by cutting and ligating the branch point. The blood vessel can then be reconstructed in situ to utilize the increased length (e.g., for forming a basilic vein transposition hemodialysis access site when a shorter segment is not optimal).

These and other objects, features, aspects and advantages of the present invention will become apparent to those skilled in the art from the following detailed description, which, taken in conjunction with the annexed drawings, discloses preferred embodiments of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

Referring now to the accompanying drawings which form a part of this original disclosure:

1A is a schematic diagram of a pump-conduit assembly according to a first embodiment of the system and method of the present invention;

1B is a schematic diagram of the pump-conduit assembly shown in FIG. 1A when applied to the circulatory system of a patient according to the first embodiment of the present invention;

FIG1C is an enlarged view of a portion of FIG1B ;

2A is a schematic diagram of a pump-conduit assembly according to a second embodiment of the system and method of the present invention;

2B is a schematic diagram of the pump-conduit assembly shown in FIG. 2A when applied to the circulatory system of a patient according to a second embodiment of the present invention;

FIG2C is an enlarged view of a portion of FIG2B ;

3 is a schematic diagram of a pump-conduit assembly according to a third embodiment of the system and method of the present invention as applied to the circulatory system of a patient;

4A is a schematic diagram of a pump-catheter assembly according to a fourth embodiment of the system and method of the present invention;

4B is a schematic diagram of the pump-catheter assembly shown in FIG. 4A when applied to the circulatory system of a patient according to a fourth embodiment of the present invention;

5A is a schematic diagram of a pump-conduit assembly according to a fifth embodiment of the system and method of the present invention;

5B is a schematic diagram of the pump-conduit assembly shown in FIG. 5A when applied to the patient's circulatory system according to a fifth embodiment of the present invention;

6 is a schematic diagram of a pump-pipe assembly according to a sixth embodiment of the system and method of the present invention;

7 is a schematic diagram of a pump-pipe assembly according to a seventh embodiment of the system and method of the present invention;

8 is a schematic diagram of a pump-pipe assembly according to an eighth embodiment of the system and method of the present invention;

FIG9 is a schematic diagram of a pump operated in conjunction with a control unit for use in any of the above-mentioned embodiments;

FIG10 is a flow chart of a method according to the first and third embodiments of the present invention;

FIG11 is a flow chart of a method according to the second and fourth embodiments of the present invention; and

FIG12 is a flow chart of a method according to a fifth embodiment of the present invention.

FIG13 is a flow chart of a method according to the sixth and seventh embodiments of the present invention.

FIG14 is a flowchart of a method according to an eighth embodiment of the present invention.

DETAILED DESCRIPTION

The system and components of the present application relate to the method for increasing the total diameter and lumen diameter of vein and artery continuously.More specifically, in various embodiments, the application relates to the method for pumping blood (for example, introducing blood or extracting blood from selected peripheral vein or peripheral artery) in a manner that the diameter of selected vein or artery continuously increases.Method disclosed herein can also increase the total diameter and lumen diameter of the selected section of vein or artery by the average blood velocity and/or peak blood velocity and average wall shear stress and/or peak wall shear stress that are enough to continuously increase the period of the total diameter and lumen diameter of the selected section of this vein or artery.These methods can therefore be used to form a vascular access site, a bypass graft or to carry out other vascular surgery or procedures for hemodialysis, wherein larger vein or artery diameter and/or larger vein or artery length are with expectation.

In various embodiments, methods and systems are provided herein that increase the velocity of blood in a peripheral vein or artery and the wall shear stress (WSS) on the endothelium of the peripheral vein or artery by using a pump. Also described are methods and systems that remove or "pull" blood from a donor vessel so that the velocity and WSS of the blood are increased in the donor vessel (artery or vein).

Preferred embodiments of the present invention will now be explained with reference to the accompanying drawings. It will be apparent to those skilled in the art from this disclosure that the following descriptions of the embodiments of the present invention are provided for illustration only and not for the purpose of limiting the invention as defined by the appended claims and their equivalents.

1-4 , a system 10 for increasing the overall diameter of a peripheral vein is shown in use with a patient 20. The system 10 draws deoxygenated venous blood from the patient's venous system 22 and discharges the blood into a recipient peripheral vein 30. The system 10 also increases the velocity of the blood in the recipient peripheral vein 30 and increases the WSS applied to the endothelium of the recipient peripheral vein 30 to continuously increase the diameter of the recipient peripheral vein 30, located in, for example, an arm 24 or a leg 26. The diameter of a blood vessel, such as a peripheral vein, can be determined by measuring the diameter of the lumen (the lumen is the open space in the center of the vessel through which blood flows) or by measuring the overall diameter of the vessel (which includes the center of the vessel through which blood flows and the walls of the vessel).

When used to describe changes in the total diameter and lumen diameter of an artery or vein, the terms "sustained increase," "sustained increase," or "sustained expansion" are used herein to mean that even if the blood pump is turned off, an increase in the total diameter or lumen diameter of the blood vessel can still be observed compared to the total diameter or lumen diameter of the blood vessel before the blood pumping period. In other words, the total diameter or lumen diameter of the blood vessel has increased regardless of the pressure generated by the blood pump.

For the purposes of this application, the diameter of the lumen of a blood vessel through which blood flows is referred to as the "lumen diameter." The diameter of a blood vessel can also be determined by measuring the diameter in a manner that includes the wall of the vessel. For the purposes of this application, this measurement is referred to as the "total diameter." The present invention relates to simultaneously and continuously increasing the total diameter and lumen diameter of a peripheral vein or artery by causing blood (preferably with low pulsatility) to move into a peripheral recipient vein, thereby increasing the velocity of the blood in the peripheral recipient vein and increasing the WSS on the endothelium of the peripheral recipient vein. Systems and methods are described in which the velocity of the blood in the peripheral recipient vein and the WSS on the endothelium of the peripheral recipient vein are increased by using a pump. Preferably, the pump actively discharges blood into the peripheral recipient vein in a manner that the pumped blood has reduced pulsatility (e.g., when the pulse pressure is lower than the pulse pressure of the blood in the peripheral artery). For example, the pump can remove or pull blood from the blood vessel or discharge or push blood into the blood vessel so that the increased WSS imposed on the blood vessel causes a continuous increase in total diameter and lumen diameter. As used herein, "pulsatility" and "pulsatility index" refer to a measure of the fluctuation of blood velocity in a vessel, which is equal to the difference between the peak systolic velocity and the minimum diastolic velocity divided by the average velocity during the cardiac cycle.

The systems and methods described herein increase the average and peak WSS levels in peripheral veins. The normal WSS of a vein is in the range of 0.076Pa and 0.76Pa. The systems and methods described herein are configured to increase the average WSS levels in a recipient's peripheral vein to a range from about 0.76Pa and 23Pa, preferably to a range between 2.5Pa and 10Pa. In some cases, a sustained average WSS of less than 0.76Pa can increase the total diameter and lumen diameter of the vein, but at a too small amount and too slow rate that is not widely accepted by clinical practice. A sustained average WSS level and/or peak WSS level greater than 23Pa may cause denudation (loss) of the venous endothelium, which is known to hinder the sustained increase in the total diameter and lumen diameter of the blood vessel in response to an increase in blood velocity and WSS. The method of the present application relates to pumping blood for any amount of time sufficient to cause dilation. For example, blood is pumped in a manner that increases WSS for about 1 day and 84 days, or preferably for between about 7 and 42 days, to produce a sustained increase in total diameter and lumen diameter in the recipient peripheral vein, so that a vein that was initially unqualified or non-optimal for use as a hemodialysis access site or bypass graft due to a small vein diameter becomes useful or better. In one embodiment, the blood pumping process can be performed in a static manner for a period of time. For example, the process can be performed for a period of 42 days, and then the recipient vein or artery is used to form a hemodialysis access site. In this example, the blood pump can be implanted at a suitable location and then started to drain blood into and/or remove blood from the blood vessel for a period of time without any subsequent adjustments.

In various other embodiments, the blood pumping process can be monitored and adjusted periodically, either manually or automatically. For example, a pump parameter (e.g., pump speed or impeller rpm) can be adjusted every second, minute, hour, day, several days, week, or several weeks (or at another time interval) to account for changes such as an increase in the total diameter and lumen diameter of the target vessel before a desired continuous increase in the total diameter and lumen diameter is achieved. The system can include a software program that analyzes information collected by the system and automatically adjusts the pump parameter (e.g., pump speed, impeller rpm, or outflow conduit pressure) to account for changes (e.g., a continuous increase in the total diameter and lumen diameter of the target vessel) before a desired continuous increase in the total diameter and lumen diameter is achieved in the target vessel. For purposes of this application, a "target vessel," "target blood vessel," "target vein," or "target artery" refers to a specific segment of an artery or vein that is intended to experience a continuous increase in total diameter and lumen diameter when the pump-conduit assembly is implanted, configured, and operated in a manner that results in a continuous increase in total diameter and lumen diameter of the artery and vein in that specific segment.

The systems and methods described herein also increase the mean and peak velocity of blood in peripheral veins and peripheral arteries. At rest, the mean velocity of blood in the cephalic vein of a human being generally ranges between 5 and 9 cm/s (0.05 and 0.09 m/s). For the systems and methods described herein, the mean velocity of blood in the peripheral veins is increased to a range between 10 cm/s and 120 cm/s (0.1 and 1.2 m/s), preferably to a range between 25 cm/s and 100 cm/s (0.25 and 1.0 m/s), depending on the desired rate of increase in the total diameter and lumen diameter of the treated vein. Depending on the initial diameter of the peripheral vein and the desired post-treatment diameter of the peripheral vein, the mean blood velocity is increased for a period of between 1 day and 84 days, or preferably between 7 days and 42 days, to cause a sustained increase in the overall diameter and lumen diameter of the peripheral vein, such that a vein that was initially unqualified or non-optimal for use as a hemodialysis access site or bypass graft due to a small vein diameter becomes useful or more optimal. This can also be achieved by intermittently increasing the mean blood velocity during treatment with intervening periods of normal mean blood velocity.

At rest, the average velocity of blood in the brachial artery is generally in the range of between 10 and 15 cm/s (0.1 and 0.15 m/s). For the systems and methods described herein, the average velocity of blood in the peripheral artery is increased to a range of between 10 cm/s and 120 cm/s (0.1 and 1.2 m/s), preferably to a range of between 25 cm/s and 100 cm/s (0.25 and 1.0 m/s), depending on the desired rate of increase in the total diameter and lumen diameter of the treated artery. Depending on the initial diameter of the artery and the desired post-treatment diameter of the artery, the average blood velocity is increased for a period of between 1 day and 84 days, or preferably between 7 days and 42 days, to cause a sustained increase in the total diameter and lumen diameter of the peripheral donor artery, such that an artery that was initially unqualified or non-optimal for use as a hemodialysis access site or bypass graft due to its small arterial diameter becomes useful or more optimal. This may also be achieved by intermittently increasing the mean blood velocity during treatment with intervening periods of normal mean blood velocity.

Studies have shown that the variation in the baseline hemodynamic force and hemodynamic force in vein and artery plays a key role in determining the total diameter and lumen diameter of these veins and arteries.For example, the continuous increase of blood velocity and wall shear stress (WSS) can cause the continuous increase of the total diameter and lumen diameter of vein and artery.The blood velocity and WSS that rise are sensed by endothelial cells, and this cell triggers signal mechanism, and this mechanism causes the stimulation of vascular smooth muscle cells, the attraction of monocytes and macrophages and the synthesis and release of the protease that can make the component degradation of the extracellular matrix such as collagen and elastin.Therefore, the present invention relates to increasing blood velocity and WSS in the period of continuous increase of the total diameter and lumen diameter of the vein and artery that is enough to cause vein and artery reconstruction and processing.

Assuming Hagen-Poiseuille flow in the vessel (ie, laminar flow with a fully developed parabolic velocity profile), the WSS can be determined using the following formula:

WSS(Pa)＝4Qμ/πR ³ , where:

Q = flow rate (m ³ /s)

μ＝blood viscosity (Pa/s)

R = Radius of blood vessel (m)

The systems and methods described herein increase WSS levels in peripheral veins and arteries. The normal average WSS for veins is in the range of 0.076 Pa and 0.76 Pa. To permanently increase the total diameter and lumen diameter of veins, the systems and methods described herein increase the average WSS levels to a range of 0.76 Pa and 23 Pa, preferably to a range of 2.5 Pa and 7.5 Pa. The normal average WSS for arteries is in the range of 0.3 Pa and 1.5 Pa. To permanently increase the total diameter and lumen diameter of arteries, the systems and methods described herein increase the average WSS levels to a range of 1.5 Pa and 23 Pa, preferably to a range of 2.5 Pa and 10 Pa. Preferably, the average WSS increase lasts for a period of between 1 day and 84 days to cause a sustained increase in the total diameter and lumen diameter of the target vessel, allowing vessels that are initially unqualified or suboptimal for use as hemodialysis access sites or bypass grafts due to small vein or artery diameters to become usable or more optimal. This can also be achieved by intermittently increasing mean WSS during treatment with intervening periods of normal mean WSS.

In some cases, an average WSS level of less than 0.76 Pa in a recipient or donor peripheral vein can increase the total diameter and lumen diameter of these blood vessels, but only increases to a too small degree and at a too slow rate that is unacceptable for conventional clinical practice. Similarly, an average WSS level of less than 0.3 Pa in a donor peripheral artery can increase the total diameter and lumen diameter of these blood vessels, but only increases to a too small degree and at a too slow rate that is unacceptable for conventional clinical practice. WSS levels higher than about 23 Pa in a recipient or donor peripheral vein or in a donor artery may cause the denudation (loss) of the endothelium of the vein and artery. Denudation of the known vascular endothelium can hinder the continuous increase in the total diameter and lumen diameter of a blood vessel, although this increases blood velocity and WSS. The increased WSS causes a sufficient continuous increase in the total diameter and lumen diameter in the vein and artery processed, making it useful or better for initially unqualified or non-optimal veins and arteries for use as hemodialysis access sites or bypass grafts due to small vessel diameters. The diameter of the recipient vein can be determined intermittently, for example every 1-14 days, to allow pump speed adjustment to optimize the continued increase in the overall diameter and lumen diameter of the vein during treatment.

The systems and methods described herein also increase the velocity of blood in peripheral veins, and in some cases, peripheral arteries. At rest, the average velocity of blood in the cephalic vein of a human being is generally between 5 and 9 cm/s (0.05 and 0.09 m/s). For the systems and methods described herein, the average velocity of blood in the peripheral veins is increased to a range between 10 cm/s and 120 cm/s (0.1 and 1.2 m/s), preferably to a range between 25 cm/s and 100 cm/s (0.25 m/s and 1.0 m/s), depending on the initial diameter of the vein, the desired post-treatment diameter of the vein, and the planned length of time for treatment (with the increased average WSS).

At rest, the average velocity of blood in the brachial artery is generally between 10 and 15 cm/s (0.1 and 0.15 m/s). For the systems and methods described herein, the average velocity of blood in the peripheral arteries is increased to a range between 10 cm/s and 120 cm/s (0.1 and 1.2 m/s), preferably to a range between 25 cm/s and 100 cm/s (0.25 m/s and 1.0 m/s), depending on the initial diameter of the artery, the desired treated diameter of the artery, and the planned length of time for treatment (with elevated WSS). Preferably, the blood velocity is increased for a period of between 1 day and 84 days, or preferably between 7 days and 42 days, to cause a sustained increase in the total diameter and lumen diameter in the peripheral recipient or donor vein or artery, so that veins and arteries that were initially unqualified or non-optimal for use as hemodialysis access sites or bypass grafts due to small vein diameters become useful or better. In some cases, average blood velocity levels below 15 cm/s (0.15 m/s) in a recipient or donor peripheral vein or in a donor artery can increase the total diameter and lumen diameter of these vessels, but only to an extent that is too small and at a rate that is too slow to be acceptable for conventional clinical practice. Blood velocity levels above about 100 cm/s (1 m/s) in a recipient or donor peripheral vein or in a donor artery can cause denudation (loss) of the endothelium of the veins and arteries. Denudation of the vascular endothelium is known to hinder a sustained increase in total diameter and lumen diameter, although this also increases blood velocity. Increased blood velocity causes sufficient sustained increase in total diameter and lumen diameter in veins and arteries to render veins and arteries that were initially unqualified or non-optimal for use as hemodialysis access sites or bypass grafts due to their small diameters useful or better.

The blood pumping process can be monitored and adjusted regularly. For example, before achieving the desired sustained increase in total diameter and lumen diameter, pump parameters (e.g., pump speed, impeller revolutions per minute, or conduit outflow pressure) can be adjusted every 7 days (or at other intervals) to account for changes in the target peripheral vein or artery (e.g., increased total diameter and lumen diameter). As an additional example, the system can include a software program that analyzes information collected by the system and automatically adjusts pump parameters (e.g., pump speed, impeller revolutions per minute, or outflow conduit pressure) to account for changes (e.g., increased total diameter and lumen diameter) before achieving the desired sustained increase in total diameter and lumen diameter.

1A-1C, 2 and 3, system 10 includes a pump-tubing assembly 12 for moving deoxygenated venous blood from a donor vein 29 of a patient's venous system 22 to a peripheral or recipient vein 30. In various embodiments, the peripheral or recipient vein 30 can be the cephalic vein, radial vein, median vein, ulnar vein, antecubital vein, median cephalic vein, median basilic vein, basilic vein, brachial vein, small saphenous vein, great saphenous vein, or femoral vein. Other veins that may be useful in forming a hemodialysis access site or bypass graft or for other vascular surgical procedures requiring the use of a vein can be used. The pump-tubing assembly 12 delivers the deoxygenated blood to the peripheral or recipient vein 30, also referred to as the target vein. The increased velocity of the blood 34 and the increased WSS in the peripheral vein 30 cause the peripheral recipient vein 30 to enlarge over time, which can manifest as an increased overall diameter, an increased lumen diameter, or an increased length. Thus, the system 10 and method 100 of the present invention (see Figures 10-11) advantageously continuously increases the diameter of a peripheral recipient vein 30 so that it can be used, for example, to construct an AVF or AVG access site for hemodialysis or as a bypass graft.

As used herein, deoxygenated blood is the blood that has passed through the capillary system and has been oxygenated by the surrounding tissue and then passed into the venous system 22. As used herein, peripheral vein 30 refers to any vein that a part resides in the chest, abdominal cavity or pelvic outside. In the embodiment shown in Figure 1B and Figure 2B, peripheral recipient vein 30 is the cephalic vein. However, in other embodiments, peripheral recipient vein 30 can also be radial vein, median vein, ulnar vein, antecubital vein, median cephalic vein, median basilic vein, basilic vein, brachial vein, small saphenous vein, great saphenous vein or femoral vein. Except peripheral vein, other veins that may be useful in forming hemodialysis access site or bypass graft or other useful veins for other vascular surgeries that need to use veins can also be used, including those that reside in the chest, abdominal cavity and pelvis.

In order to reduce the pulsatility of blood introduced into a peripheral recipient vein and/or to provide a low-pulsatility blood flow to a peripheral recipient vein, a variety of pulsatility suppression techniques can be used. Pulsatility is suppressed to reduce the cyclic stretching of smooth muscle cells in the recipient vein, which has been shown to lead to increased venous smooth muscle proliferation, a major factor in venous neointimal hyperplasia and venous stenosis. By way of example, and not limitation, such techniques include: modulating the head-flow characteristics of a blood pump; adding an elastic reservoir or windkessel segment to the inflow or outflow conduit; increasing compliance to the inflow or outflow conduit; regulating the pump speed, such as increasing the pump speed during diastole and decreasing the pump speed during systole; or adding a counterpulsation effect to the inflow or outflow conduit or pump.

AVFs created using the cephalic vein at the wrist are a preferred form of vascular access for hemodialysis, but this vein often has an insufficient or suboptimal diameter, making AVF creation at this location unfavorable. Therefore, the present invention facilitates the creation of AVFs in the wrist of ESRD patients and increases the percentage of ESRD patients receiving hemodialysis using a wrist AVF as a vascular access site.

Pump-conduit assembly 12 includes a blood pump 14 and combined conduits 16 and 18, i.e., inflow conduit 16 and outflow conduit 18. Blood pumps have been developed as components of vascular assist devices (VADs) and have been miniaturized to treat adult and pediatric patients with moderate heart failure.

In one embodiment, a blood pump system comprising a pump, a tubing system, a control system, and a power supply can be used, wherein the pump has a configuration suitable for increasing blood velocity and WSS in peripheral arteries and veins, as described in a related, commonly filed U.S. patent application entitled "Blood Pump Systems and Methods." In this embodiment, the pump is a centrifugal pump and a pump system that can be fluidically connected to a vessel or location in the cardiovascular system (including, but not limited to, central and peripheral arteries and veins and the right atrium) and remove blood from the first vessel or location in the cardiovascular system, and fluidly connected to a second vessel or location in the cardiovascular system (including, but not limited to, central and peripheral arteries and veins and the right atrium) and move blood into the second vessel or location in the cardiovascular system. The tubing system includes an inflow conduit for conveying blood from the vessel or location in the cardiovascular system to the pump, and an outflow conduit for conveying blood from the pump to the second vessel or location in the cardiovascular system. The blood pump system also includes a control system for regulating parameters of the pump and system, including, but not limited to, the speed of the blood pump, the speed of the impeller, and the outflow conduit pressure. For certain embodiments, the control system includes a sensor in the blood pump, tubing, or the patient's vascular system that measures at least one of the following: the power or current required to operate the pump under certain operating conditions; blood velocity; blood flow rate; resistance to blood flow into or out of the peripheral blood vessels; blood pressure or pulse pressure (in the inflow tubing, outflow tubing, or in an adjacent vessel), pulsatility index, and combinations thereof. The blood pump system is primarily configured to pump a sufficient amount of blood for a sufficient period of time such that a desired and elevated WSS and blood velocity are achieved within the target vessel and maintained for a period of time sufficient to result in an increase in the overall diameter, lumen diameter, or length of the target vessel. The WSS can be determined using the average flow through the pump system and the diameter of the target vessel. In this setting, the average flow rate out of the pump can be estimated from measurements of the power required to drive the pump. In this context, an assumption is made that all flow streams originate from (for donor vessels) or go to (for peripheral recipient veins) the target vein.

The pump can be implanted in the patient or maintained external to the patient and is typically connected to one or more conduits, a controller, and a power source. Referring to FIG9 , a schematic diagram of the pump system 10 is shown. The pump 14 can be a rotary pump, such as an axial flow pump, a mixed flow pump, or a centrifugal pump. Without intending to be particularly limiting, the bearings of the pump 14 can be configured to have a magnetic field, a hydrodynamic force, or use mechanical contact bearings such as double pin bearings. Pumps used in pediatric VAD systems or other low-flow VAD systems, including the blood pump systems described above, can be used. Alternatively, the pump 14 can be an extracardiac pump, such as that shown and described in U.S. Patent Nos. 6,015,272 and 6,244,835, both of which are incorporated herein by reference. These pumps are suitable for use in the system 10 and for performing the method 100 of the present invention as shown in FIG10-14 . The pump 14 has an inlet 38 for receiving deoxygenated blood drawn into the inflow conduit 16 and an outlet 40 for the blood stream 34 to exit the pump 14 and move into the outflow conduit 18. Regarding pumps suitable for use as the pump 14 of the present invention in pediatric VAD systems or other low-flow VAD systems, these pumps can be sized to be as small as approximately the size of an AA battery or the diameter of a $0.50 or quarter coin and can weigh as little as about 35 grams or less. These pumps are designed to pump, for example, approximately 0.05 to 1.0 L/min, 0.1 to 1.5 L/min, or 1.0 to 2.5 L/min. For the aforementioned pumps designed to operate within a higher flow range, these pumps can be modified to reduce this range to as low as 0.05 L/min for use in small-diameter peripheral veins and arteries. The blood-contacting surface of the pump 14 can include _Ti6Al4V , _Ti6Al7Nb , or other commercially pure titanium alloys or metals, alternative titanium alloys, biocompatible ceramics such as _aluminum oxide, silicon carbide, or zirconium oxide, or biocompatible polymers. In certain embodiments _, the blood-contacting surface can have one or more coatings and surface treatments, including an anti-thrombotic coating that reduces the accumulation of thrombi on the blood-contacting surface. Thus, any of a variety of pumping devices may be used, as long as it can be fluidly connected to the vascular system and can safely pump a sufficient amount of blood to achieve the desired blood velocity and WSS in a target vessel, such as a recipient vein or donor vein or artery.

The pump 14 includes various components 42 and a motor 44, as shown in FIG9 . The various components 42 and the motor 44 can be those common to pumps of a VAD or a blood pump system. For example, the components 42 include one or more of a shaft, an impeller, impeller blades, bearings, stator vanes, a rotor, or a stator. The rotor can be magnetically suspended, or the rotor position can be controlled by hydrodynamic forces or using mechanical contact bearings such as double pin bearings. The motor 44 can include a stator, a rotor, a coil, and a magnet. The motor 44 can be any suitable electric motor, for example, a multiphase motor controlled via pulse width modulated current. In operation, the pump 14 can create suction within the inflow conduit 16 to pull blood from a blood vessel such as a peripheral artery, a peripheral vein 30, a central vein, or the right atrium 31.

The system 10 and method 100 may use one or more of the pumps described in the following publications: "The PediaFlow ^™ Pediatric Ventricular Assist Device," P. ^Wearden et al., Pediatric Cardiac Surgery Annual, pp. 92-98, 2006; J. Wu et al., "Designing with Heart," ANSYS Advantage, Vol. 1, No. 2, pp. s12-s13, 2007; and J. Baldwin et al., "The National Heart, Lung, and Blood Institute Pediatric Circulatory Support Program," Circulation, Vol. 113, pp. 147-155, 2006. Other examples of pumps that may be used as pump 14 include: Novacor, PediaFlow, Levacor, or MiVAD from Heart, Inc.; Debakey Heart Assist 1-5 from Micromed, Inc.; HeartMate XVE, HeartMate II, HeartMate III, IVAD, PVAD, CentriMag, PediMag, or UltraMag from Thoratec, Inc.; Impella, BVS5000, AB5000, or Symphony from Abiomed, Inc.; TandemHeart from CardiacAssist, Inc.; VentrAssist from Ventracor, Inc.; Incor or Excor from Berlin Heart, GmbH; Duraheart from Terumo, Inc.; HVAD or MVAD from HeartWare, Inc.; Jarvik 2000 Flowmaker or Pediatric Jarvik from Jarvik Heart, Inc. 2000Flowmaker; Gyro C1E3 from Kyocera, Inc.; CorAide or PediPump from Cleveland Clinic Foundation; MEDOS HIA VAD from MEDOS Medizintechnik AG; pCAS from Ension, Inc.; Synergy from Circulite, Inc.; and BP-50 and BP-80 from Medtronic, Inc. The pumps can be monitored and adjusted manually or using a software program, application, or other automated system. The software program can automatically adjust the pump speed (including the revolutions per minute of the impeller) to maintain a desired blood velocity and WSS in the target vessel of the recipient vein, donor artery, or donor vein. Alternatively, the diameter of the target vessel and the blood flow rate in the blood pump system or the target vessel can be checked periodically, and the pump can be manually adjusted to maintain the desired blood velocity and WSS level in the target vessel.

In one embodiment, the average blood velocity is determined by averaging multiple discrete measurements of blood velocity by summing the discrete measurements and dividing the sum by the number of measurements. The average blood velocity can be calculated by taking multiple measurements over a period of seconds, minutes, or hours.

In another embodiment, an average wall shear stress (WSS) is determined by taking a series of discrete measurements, making multiple discrete determinations of the average WSS (using those measurements), summing the discrete WSS determinations, and dividing the sum by the number of determinations. The average WSS can be calculated by taking multiple measurements and making multiple discrete determinations over a period of seconds, minutes, or hours.

Blood received and pumped by pump 14 travels through one or more of synthetic tubing 16 and 18. Synthetic tubing 16 and 18 are connected to pump 14 using connectors that provide a reliable, leak-proof fluid connection to the pump. In one embodiment, the connectors are radial compression-type connectors that compress synthetic tubing 16 and 18 against barbed fittings coupled to inlet 38 and/or outlet 40 of pump 14.

The synthetic conduits 16 and 18 may be of any material or combination of materials, so long as the conduits 16 and 18 exhibit the desired properties, such as flexibility, sterility, kink resistance, compression resistance, and can be fluidically connected to a blood vessel or inserted into the lumen of a blood vessel via surgical anastomosis as needed. All or a portion of the synthetic conduits 16 and 18 may be constructed of materials commonly used to make hemodialysis catheters, such as polyvinyl chloride, polyethylene, polyurethane, and/or silicone. All or a portion of the synthetic conduits 16 and 18 and other portions of the system 10 may be reinforced with nitinol or another shape memory alloy or radially expandable metal or material. Preferably, a layer of braided nitinol is wrapped around the synthetic conduits 16 and 18 or incorporated into the wall of the conduits. Alternatively, a coil of nitinol may be wrapped around or incorporated into all or a portion of the synthetic conduits 16 and 18. All or a portion of the synthetic tubing 16 and 18 can be constructed from polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), and/or Dacron, preferably reinforced to make these sections of the synthetic tubing 16 and 18 less susceptible to kinking and clogging. Furthermore, the synthetic tubing 16 and 18 preferably exhibits properties necessary for tunneling (if desired), for example, including a lubricious outer surface coating such as Harmony ^™ advanced lubricious coating, and having a luminal surface that resists thrombosis. The luminal surface can be coated with an antithrombotic agent or material. For example, the luminal surface can be coated with a heparin-based antithrombotic agent coating provided by BioInteractions Ltd., or a heparin-coated Applause ^™ provided by SurModics, Inc.

As another example, all or part of the synthetic tubing 16 and 18 may have an outer layer composed of a different material than the lumen layer. The synthetic tubing 16 and 18 may be coated with silicone to aid removal from the body and avoid latex allergies. Furthermore, the outer surfaces of the synthetic tubing 16 and 18 may have an antimicrobial coating. For example, the outer surfaces of the synthetic tubing 16 and 18 or the outer surfaces of the pump or lead may be coated with a surface-active antimicrobial coating provided by BioInteractions Ltd.

In some embodiments, the connection between the synthetic tubing 16 or 18 and the vein 29 or 30 is made using conventional surgical anastomosis, using sutures in a running or divided manner (hereinafter described as an "anastomotic connection"). The anastomotic connection can also be made using surgical clips and other standard methods of making anastomosis. In some embodiments, the tubing is composed of a section made of materials commonly used to make hemodialysis catheters, such as polyvinyl chloride, polyethylene, polyurethane and/or silicone, and physically joined to a section made of polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylene (ePTFE) and/or Dacron, which can be connected to a peripheral vein or artery by an anastomotic connection.

In other embodiments, the portions of the inflow and outflow conduits 16, 18 that are configured for insertion into the lumen of a vascular system may have self-expanding or radially expanding walls (e.g., as may be achieved by incorporating nitinol) such that the diameter of the intravascular portions of the inflow and outflow conduits 16, 18 will match the diameter of the vasculature at that location, for example, as seen in the self-expanding section of a Hybrid Vascular Graft.

1A-1C , the inflow conduit 16 has a first end 46 configured to be fluidically connected to a donor vein 29 or the right atrium 31 of the heart, and a second end 48 configured to be fluidically connected to the inlet 38 of the pump 14. The donor vein 29 may include the antecubital vein, basilic vein, brachial vein, axillary vein, subclavian vein, jugular vein, brachiocephalic vein, superior vena cava, lesser saphenous vein, greater saphenous vein, femoral vein, common iliac vein, external iliac vein, superior vena cava, inferior vena cava, or other vein capable of providing sufficient blood flow to the pump to cause a sustained increase in the total diameter and lumen diameter of the target vessel (in this case, the recipient peripheral vein 30). The outflow conduit 18 has a first end 52 configured to be fluidically connected to the peripheral recipient vein 30 and a second end 54 configured to be fluidly connected to the outlet 40 of the pump 14. In various embodiments, the first end 46 of the inflow conduit 16 and the first end 52 of the outflow conduit 18 are chamfered at an angle between 15° and 75°, and preferably 45°.

The pump-conduit assembly 12 is configured to move blood from the donor vein 29 to the peripheral recipient vein 30 in a manner that increases the mean blood velocity, peak blood velocity, and WSS in the target vein (in this case, the peripheral recipient vein 30) to desired levels and for a period of time sufficient to cause a sustained increase in the total diameter and lumen diameter of the peripheral recipient vein. In certain embodiments, a portion of the composite conduits 16, 18 may be external to the patient 20. Referring to Figures 1A-1C and 3, the first end 46 of the inflow conduit 16 and the first end 52 of the outflow conduit 18 are configured for anastomotic connections. As shown in Figures 1B and 1C, the first end 46 is fluidly connected to the internal jugular vein (which serves as the donor vein 29) via an anastomotic connection, and the first end 52 of the outflow conduit 18 is fluidly connected to the cephalic vein (which serves as the peripheral recipient vein 30) via an anastomotic connection.

2A-2C , the first end 46 of the synthetic inflow conduit 16 is configured as a catheter. The fluid connection between the synthetic inflow conduit 16 and the venous system is performed by positioning the top of the catheter portion 50 of the synthetic inflow conduit within the superior vena cava 27, hereinafter described as a "catheter connection." When a catheter connection is made with a donor vein 29 (in this case, the superior vena cava 27), the catheter portion 50 of the synthetic inflow conduit 46 can enter the venous system at any position where the diameter of the venous lumen is sufficient to accommodate the catheter portion 50. The top of the catheter portion 50 can be placed at any position where enough blood can be drawn into the catheter to provide the desired blood flow 34 to the recipient vein 30. Preferred locations for the top of the catheter portion 50 include, but are not limited to, the brachiocephalic vein, the superior vena cava 27, and the right atrium 31. In the embodiment shown in FIG. 2B-2C , the system 10 draws deoxygenated blood from the superior vena cava 27 of the patient 20 and discharges it to the cephalic vein 30 of the arm 24.

In another embodiment, shown in FIG3 , the system 10 draws deoxygenated venous blood from a donor vein 29 (in this case, the more proximal portion of the great saphenous vein) and drains it into a peripheral recipient vein 30 in the leg 26 (in this case, the more distal portion of the great saphenous vein), thereby increasing the blood velocity and WSS in the recipient peripheral vein to a desired level for a period of time sufficient to cause a sustained increase in the lumen and total diameter of the recipient great saphenous vein 30. In settings where it may be desirable to increase retrograde venous flow into the blood pump system, one or more venous valves between the inflow line, the donor vein, or the connection to the right atrium can be rendered incompetent, allowing blood to flow in a retrograde direction in this segment of the donor vein and then into the inflow line. In the embodiment shown in FIG3 , the inflow line 16 is fluidly connected to the proximal great saphenous vein 29 of the patient 20 via an anastomotic connection. The pumping of blood to the peripheral recipient vein 30 (in this case, the distal great saphenous vein) and the increases in mean blood velocity, peak blood velocity, and mean WSS are continued for a period of time sufficient to cause a sustained increase in the total diameter and lumen diameter of the recipient great saphenous vein segment 30 to facilitate its harvesting and autologous transplantation as part of a surgical procedure to form a cardiac or peripheral bypass graft, or other surgical procedure requiring autologous transplantation of a portion of the patient's vein.

4A and 4B illustrate another embodiment of the system 10. Referring to FIG4A , in another embodiment, an external or implanted pump 114 is attached to two dedicated catheters that act as conduits, namely, an inflow conduit 55 and an outflow conduit 56, to form a conduit-pump assembly (which may alternatively be described as a catheter-pump assembly) 13. The pump 114 draws deoxygenated blood from the donor vein 29 into the lumen of the inflow conduit 55 and then drains blood from the outflow conduit 56 into the lumen of the peripheral recipient vein 30, thereby increasing the blood velocity and WSS in the peripheral recipient vein 30.

Referring to Figures 4A and 4B, pump-pipeline (or pump-catheter) assembly 13 is configured to increase the blood velocity and WSS in the venous segment d. Inflow conduit 55 and outflow conduit 56 can be optionally joined in all or some parts and can be percutaneously inserted into the lumen of the recipient's peripheral vein 30 to eliminate the need for more invasive surgical procedures. In certain embodiments, a portion of one or both conduits can be tunneled subcutaneously under the skin, wherein the tunneled section is positioned between the intravascular segment and the external segment to reduce the risk of infection. The external portions of conduits 119 and 120 and the external pump 114 can be affixed to the body. Alternatively, the pump and conduit can be implanted, and the leads leading to the controller leave the skin. The pump 114 can be connected to a power source and operate in a manner that increases the blood velocity 34 and WSS in the segment d of the recipient's peripheral vein 30 for a period of time sufficient to cause a continuous increase in the total diameter and lumen diameter of the segment d. Once the desired amount of sustained increase in overall and lumen diameter has occurred in segment d of the recipient peripheral vein 30, the pump-tubing assembly 12 is removed and, at the same time as the pump-tubing assembly is removed or at a later time, at least a portion of the enlarged (increased overall or lumen diameter or increased length) segment d of the recipient peripheral vein 30 can be used for a surgical procedure to form a hemodialysis access site or bypass graft. Alternatively, the enlarged vein can be used for other surgeries or procedures.

5A and 5B , a system 10 for increasing the overall diameter of a peripheral vein is shown in use with a patient 20. System 10 draws oxygenated arterial blood from a peripheral artery 221 of the patient and discharges the blood into a recipient peripheral vein 30. System 10 is configured and operative to increase the blood velocity and WSS in recipient peripheral vein 30 for a period of time sufficient to cause a sustained increase in the diameter of recipient peripheral vein 30, for example, in arm 24 or leg 26. An embodiment of system 10 is shown in which a pump 214 is implanted in arm 24. Pump 214 has an inlet 240 connected to artery 221 in arm 24 via an anastomotic connection. Pump 214 also has an outlet 238 connected to peripheral vein 30 via an anastomotic connection. Pump 214 is controlled and powered by control unit 58. In operation, pump 214 draws blood from artery 221 and pumps the blood into peripheral vein 30. This embodiment avoids the need for extended synthetic tubing and increases blood velocity and WSS in the peripheral vein 30 and peripheral artery 221, which results in a simultaneous and sustained increase in the total diameter and lumen diameter of the vein 30 and artery 221 when operated for a sufficient period of time. Specifically, the pump 214 is implanted in the forearm 24 of the patient 20. Once the desired sustained increase in total diameter and lumen diameter occurs in the recipient peripheral vein 30, the pump 214 can be removed and, during a concurrent or subsequent operation, surgery can be performed using at least a portion of the enlarged artery 221 or vein 30 to form a hemodialysis access site or bypass graft.

In other embodiments, oxygenated arterial blood can be moved from a donor artery to a recipient site. Donor arteries can include, but are not limited to, the radial, ulnar, interosseous, brachial, anterior, posterior, peroneal, popliteal, profunda, superficial femoral, or femoral arteries. Oxygenated blood can be moved from the donor artery to the recipient site passively based on inherent pressure differentials or actively by incorporating a pump into the system.

Fig. 6 shows another embodiment for using system 10 to increase the total diameter and lumen diameter of a blood vessel. In this embodiment, system 10 is configured to remove oxygenated blood from a donor artery 312 (in this case, the brachial artery) and move the blood to the superior vena cava and the right atrium 302 of the heart 304. As shown, an inflow conduit 306 is connected to the donor artery 312 fluidly. In one embodiment, a short ePTFE segment of the inflow conduit 306 that is used to fix the inflow conduit 306 to the donor artery 312 can be used to make a connection, while polyurethane is used to make the remaining segment of the inflow conduit. In other embodiments, one or both segments of the inflow conduit 306 also include nitinol, for example, to resist kinking and compression. As shown, one end of the outflow conduit 310 is connected to the pump 14, while the other end of the outflow conduit is connected to the superior vena cava and the right atrium 302 by the intravascular portion of the fluid. 6 , the pump 14 is used to increase the rate at which blood is drawn from the donor artery 312 and discharged into the right atrium 302 of the heart 304 in order to achieve a desired elevated level of blood velocity and elevated level of WSS in the donor artery 312. The pump is operated at a sufficient rate and for a sufficient time to produce a desired sustained increase in the overall diameter and lumen diameter of the donor artery, for example, a 5% increase, a 10% increase, a 25% increase, a 50% increase, or an increase of 100% or more from the initial diameter.

FIG7 illustrates another embodiment for using system 10 to increase the overall and lumen diameters of blood vessels. In this embodiment, system 10 is configured to remove oxygenated blood from a donor artery 312 (in this case, the brachial artery) and move this blood to the superior vena cava and right atrium 302 of the heart 304. As shown, in this embodiment, an inflow conduit 306 is present, one end of which is connected in fluid communication with the donor artery 312. In one embodiment, the connection to the donor artery 312 can be made using a short ePTFE segment used to secure the conduit 306 to the donor artery 312, while the remaining segments of the conduit are made of polyurethane. In other embodiments, some or all of the conduit 306 may also include nitinol, for example, to resist kinking and compression. In the embodiment of FIG7 , no pump is present, and blood is passively moved from the higher pressure donor artery 312 to the lower pressure superior vena cava and right atrium 302. The conduit 306 is configured in length and lumen diameter to achieve the desired increased blood velocity and WSS in the donor artery 312. Tubing 306 remains in place for a time sufficient to cause the desired sustained increase in the overall and lumen diameters of donor artery 300, e.g., a 5% increase, a 10% increase, a 25% increase, a 50% increase, or an increase of 100% or more from the initial diameter.

In one embodiment, as shown in Figure 7, a method for using system 10 involves a single conduit and includes entering an artery 312. One end of a conduit of conduit 306 is connected to the artery 312, and the other end of the conduit is connected to a receptor site (e.g., the right atrium 302 of a heart 304) so that at least a portion of the blood flowing in the artery is directed to the receptor site away from the artery. In this method, blood passively moves from the higher pressure artery 312 to the lower pressure right atrium 302 without the need for a pump. After a period of time, the total diameter and lumen diameter of the artery 312 increase. Then, conduit 306 is disconnected from the artery 312, and a portion of the right atrium 302 and the artery is prepared to be used as a hemodialysis access site, a bypass graft, or in another surgical procedure in which an artery is used or required.

Fig. 8 shows another embodiment for using system 10 to increase the total diameter and lumen diameter of target blood vessel.In this embodiment, system 10 is configured to remove the blood of hypoxia from donor vein 300 and move this blood to the right atrium 302 of superior vena cava or heart 304.As shown in the figure, inflow conduit 306 is connected with donor vein 300 (in this case, cephalic vein) fluid communication ground.In one embodiment, can use the short ePTFE section that inflow conduit 308 is fixed to the inflow conduit 306 of donor vein 300 to make connecting portion, use polyurethane to make the remaining section of inflow conduit simultaneously.In other embodiments, at least a portion of inflow or outflow conduit comprises nitinol, for resisting kink and compression.As shown in the figure, one end of outflow conduit 310 is connected to pump 14, and the other end of outflow conduit is connected to the right atrium 302 of heart 304 by intravascular part fluid simultaneously. 8 , the pump 14 is used to increase the rate at which blood is drawn from the donor vein 300 and discharged into the right atrium 302 of the heart 304 in order to achieve a desired elevated blood velocity and elevated WSS in the donor vein 300. The pump is operated at a sufficient rate and for a sufficient time to cause a desired sustained increase in the overall diameter and lumen diameter of the donor vein 300, for example, a 5% increase, a 10% increase, a 25% increase, a 50% increase, or an increase of 100% or more from the initial diameter. In another embodiment, one or more venous valves between the junction of the inflow conduit 308 and the donor vein 300 and the right atrium 302 can be rendered incompetent or more incompetent (using any method available to one skilled in the art) to allow blood to flow in a retrograde manner in the donor vein 300 (away from the heart) and then into the inflow conduit 308.

In other embodiments, for example when a peripheral artery is the donor vessel and a peripheral vein is the recipient vein, blood is pumped into the recipient peripheral vein with a reduced pulsatility compared to the pulsatility of the blood in the peripheral artery. For example, with the pump operating, the average pulse pressure in the recipient peripheral vein adjacent to the connection with the outflow conduit is <40 mmHg, <30 mmHg, <20 mmHg, <10 mmHg, or preferably <5 mmHg. In order to reduce pulsatility and/or provide low pulsatility flow, a variety of pulsatility suppression techniques can be used. By way of example, and not limitation, such techniques include: adjusting the head-flow characteristic of the blood pump; adding an elastic reservoir or elastic reservoir segment to the inflow or outflow conduit; increasing compliance to the inflow or outflow conduit; adjusting the pump speed, for example, increasing the pump speed during diastole and decreasing the pump speed during systole; or adding a counterpulsation effect to the inflow or outflow conduit or pump.

Referring to FIG9 , a schematic diagram of an embodiment of the pump system 10 is shown. A control unit 58 is connected to the pump 14 and is configured to control the speed of the pump 14 and collect information about the function of the pump system 10. The control unit 58 can be implanted in the patient 20, can be retained externally to the patient 20, or can have both an implanted portion and an external portion. A power source is implemented as a power unit 60 and is connected to the control unit 58 and the pump 14. The power unit 60 provides energy to the pump 14 and the control unit 58 for normal operation. The power unit 60 can be implanted in the patient 20, can be retained externally to the patient 20, or can have both an implanted portion and an external portion. The power unit 60 can include a battery 61. The battery 61 is preferably rechargeable and, in this embodiment, is charged via an electrical connector 69 to a power source. Such rechargeable batteries can also be charged using leads or via transcutaneous energy transfer (e.g., at the time of implantation). In another embodiment, a depleted rechargeable battery can be charged at a charging station connected to a wall outlet and then swapped with the depleted battery of the pump system 10. Alternatively, the electrical connector 69 may provide electrical power to the power pack 60 without the aid of the battery 61. It will be apparent to those skilled in the art from this disclosure that the control unit 58 may be configured to utilize alternative power systems and control systems.

Sensors 66 and 67 can be incorporated into the vascular system, tubing 16 and 18, pump 14, or control unit 58. Sensors 66 and 67 are connected to control unit 58 via cable 68 or can communicate wirelessly with control unit 58. Without limitation to the examples provided, sensors 66 and 67 can measure various pump, tubing, control unit, or system parameters, including the power or current required to operate the pump under certain operating conditions, blood velocity, blood flow, resistance to blood flow from a donor vessel or into a peripheral recipient vein, blood pressure or pulse pressure, pulsatility index, and combinations thereof, and can send signals to the pump or control unit 58. Control unit 58 (also referred to as a controller) can use these measurements to determine (or estimate) any one or more of the following: the lumen diameter of an adjacent target vessel in fluid communication with the tubing, flow resistance, or WSS in a target vessel, including a recipient vein, donor vein, or donor artery, and can send signals to the pump to change pump speed, impeller speed, tubing blood pressure, or other pump system parameters. For example, as the overall diameter and lumen diameter of the peripheral vein 30 receiving the pumped blood increases, the blood velocity and WSS in the peripheral vein 30 decreases, along with the resistance to blood flow 34 from the outflow tubing 18. To maintain the desired blood velocity and WSS, the pump speed can be adjusted as the overall diameter and lumen diameter of the peripheral recipient vein 30 increase over time.

As previously mentioned, the control unit can rely on measurements, including internal measurements of the current to the motor 44, as a basis for estimating blood flow, blood velocity, intraluminal pressure, or flow resistance. The control unit 58 can also include a manual controller to adjust the pump speed, impeller speed, or other pumping parameters.

The control unit 58 is operably connected to the pump-conduit assembly 12. Specifically, the control unit 58 is operably connected to the pump 14 by one or more cables 62. Utilizing the power unit 60, the control unit 58 preferably supplies a pump motor control current, such as a pulse-width modulated motor control current, to the pump 14 via the cables 62. The control unit 58 can also receive data and information from the pump 14. The control unit 58 also includes a communication unit 64 that is configured to collect data and information and to communicate the data and information, such as by telemetry transmission. In addition, the communication unit 64 is configured to receive instructions or data for reprogramming the control unit 58. Thus, the communication unit 64 is configured to receive instructions or data that are subsequently used to change the functionality of the pump 14.

The present invention provides a monitoring system consisting of a control unit 58 and sensors 66 and 67 for adjusting pump operation to maintain a desired blood velocity and WSS in the target vessel as the overall diameter and lumen diameter of the target vessel increase over time.

Preferably, pump 14 is configured to provide a blood flow rate 34 within a range of approximately 50–2500 mL/min. Pump 14 is configured to increase the average WSS in the target vein to a range between 0.76 Pa and 23 Pa, preferably to a range between 2.5 Pa and 10 Pa. Pump 14 is configured to increase the average WSS in the target artery to a range between 1.5 Pa and 23 Pa, preferably to a range between 2.5 Pa and 10 Pa. Pump 14 is configured to maintain the desired levels of blood flow, average blood velocity, and average WSS in the target vein or artery for a period of approximately, for example, 7-84 days, and preferably, approximately, for example, 7-42 days. In certain situations where a large, sustained increase in the total and lumen diameters of the vein is desired, or where the sustained increase in the total and lumen diameters of the vein occurs slowly, pump 14 is configured to maintain the desired levels of blood flow and WSS in the recipient peripheral vein 30 for more than 84 days.

The pump-conduit assembly 12 can be implanted on the right side of the patient 20, or on the left side if desired. The lengths of the conduits 16 and 18 can be adjusted for desired placement. Specifically, with respect to Figures 1B and 1C , the first end 46 of the inflow conduit 16 is fluidically connected to the right internal jugular vein 29, and the first end 52 of the outflow conduit 18 is fluidically connected to the cephalic vein 30 in the right forearm near the wrist. Specifically, with respect to Figures 2B and 2C , the first end 46 of the inflow conduit 16 is fluidically connected to the superior vena cava 27, and the first end 52 of the outflow conduit 18 is fluidically connected to the cephalic vein 30 in the right forearm 24 near the wrist. After the connections are made, pumping begins. That is, the control unit 58 begins operating the motor 44. The pump 14 pumps blood 34 through the outlet conduit 18 and into the peripheral vein 30. The control unit 58 adjusts the pumping over time by utilizing data provided by sensors 66 and 67. Figures 1A-1C , 2 , 3 , and 4 illustrate an example of system 10 pumping deoxygenated blood. 5A-5B show an example of system 10 pumping oxygenated blood. In some embodiments, blood is pumped into the recipient vein with a reduced pulsatility compared to the pulsatility of the blood in the peripheral artery. For example, with the pump operating and delivering blood into the peripheral vein, the average pulse pressure in the recipient vein is <40 mmHg, <30 mmHg, <20 mmHg, <10 mmHg, or preferably <5 mmHg. In other embodiments, blood is pumped into the recipient vein with an equal or increased pulsatility compared to the pulsatility of the blood in the peripheral artery. For these embodiments, with the pump operating, the average pulse pressure in the recipient vein adjacent to the connection to the outflow tubing is ≥40 mmHg.

In one specific embodiment shown in Figures 1B and 1C, the donor vein 29 is the jugular vein 21, preferably the internal jugular vein 21. The internal jugular vein 21 is particularly useful as the donor vein 29 because there is no valve between the internal jugular vein 21 and the right atrium 31, which allows the synthetic inflow conduit 16 to withdraw a large volume of deoxygenated blood per unit time, including withdrawing blood that flows in a retrograde manner in a portion of the jugular vein. The inflow conduit 18 is fluidly connected to the internal jugular vein 21 of the patient 20. The deoxygenated blood is removed from the internal jugular vein 21 and pumped into a peripheral recipient vein 30 in the arm 24, resulting in an increase in the velocity and WSS of the blood 34 in the peripheral recipient vein 30. In some embodiments, the blood is pumped into the recipient vein with a reduced pulsatility compared to the pulsatility of the blood in the peripheral arteries. For example, with the pump operating, the mean pulse pressure in the recipient vein adjacent to the connection to the outflow tubing is <40 mmHg, <30 mmHg, <20 mmHg, <10 mmHg, or preferably <5 mmHg.

As previously noted, FIG5B illustrates an example of system 10 withdrawing and draining oxygenated blood. Inflow conduit 240 is fluidly connected to radial artery 221 of patient 20, and outflow conduit 238 is fluidly connected to the cephalic vein, both using an anastomotic connection. Thus, oxygenated blood is removed from radial artery 221 and pumped into cephalic vein 30 in arm 24 in a manner that results in increased blood velocity and WSS in the cephalic vein for a sufficient period of time to cause a sustained increase in the total diameter and lumen diameter of recipient peripheral vein 30. In some embodiments, blood is pumped into recipient vein 30 at a reduced pulsatility compared to the pulsatility of blood in the peripheral artery. For example, with the pump operating and delivering blood to the peripheral recipient vein, the average pulse pressure in the recipient vein adjacent to the connection to the outflow conduit is <40 mmHg, <30 mmHg, <20 mmHg, <10 mmHg, or preferably <5 mmHg.

10-14, various embodiments of a method 100 increase the overall diameter and lumen diameter of a peripheral recipient vein, a peripheral donor artery, or a peripheral donor vein.

As shown in FIG10 , in an embodiment of method 100 , a physician or surgeon performs surgery to access a vein and, in step 101, connects a pump to establish fluid communication with the vein carrying deoxygenated blood. In step 102 , the pump is connected to a peripheral vein. In this embodiment, the pump-tubing assembly 12 is implanted in the neck, chest, or arm 24 of the patient 20 . In another embodiment, where the peripheral vein 30 is the great saphenous vein 30 , the pump-tubing assembly 12 is implanted in the leg 26 , pelvis, or abdominal cavity. In one example, the physician utilizes a tunneling procedure (if necessary) to subcutaneously connect two locations to fluidically connect the first end 46 of the pump-tubing assembly 12 to the donor vein 29 (in this case, the proximal great saphenous vein) and the second end of the pump-tubing assembly 12 to the peripheral recipient vein 30 (in this case, the distal great saphenous vein). In step 103 , the deoxygenated blood is pumped into the peripheral recipient vein. In step 104 , pumping continues for a period of time while the physician waits for the overall diameter and lumen diameter of the peripheral recipient vein to continue to increase. In one embodiment, after the pump is turned on to begin pumping the deoxygenated blood, the skin incision is closed as needed. In another embodiment, portions of the combined tubing 16 and 18 and the pump 14 are located outside the body. In this embodiment, the pump 14 is then activated and controlled via the control unit 58 to pump the deoxygenated blood through the pump-tubing assembly 12 and into the peripheral recipient vein 30 in a manner that increases the blood velocity and WSS in the peripheral vein 30. The operation of the pump system and the other parameters mentioned above are regularly monitored, and the control unit 58 is used to adjust the operating parameters of the pump 14 in response to changes in the peripheral recipient vein 30 (e.g., increased total diameter or lumen diameter). With regular adjustments, the pump continues to operate for an amount of time sufficient to cause a sustained increase in the total diameter, lumen diameter, or length of the peripheral vein 30, if necessary. In a subsequent procedure, the pump-tubing assembly 12 is disconnected from the patient and the pump system is removed at step 105. At step 106, the peripheral vein 30 having continuously increasing overall and lumen diameters is used to form an AVF, AVG, bypass graft, or other surgical procedure or procedure requiring a vein as determined by one skilled in the art.

As shown in Figure 11, in another embodiment of method 100, a physician or surgeon inserts the inflow catheter tubing 55 of the pump-catheter assembly into the venous system and positions it in the donor vessel position. In step 107, the physician or surgeon then inserts the outflow catheter tubing 56 of the pump-catheter assembly into the venous system and positions it in the peripheral recipient vein 30 position. In step 108, the pump is operated to pump deoxygenated blood from the donor vessel position 29 to the peripheral recipient vein position 30. In step 109, the physician then waits for the total diameter and lumen diameter of the peripheral vein segment d to increase to the desired amount. Then, in step 110, the pump-catheter assembly is removed, and in step 111, the peripheral recipient vein segment with the continuously increasing total diameter and lumen diameter is used to form an AVF, AVG, or bypass graft, or other surgical procedures or procedures requiring a vein as determined by those skilled in the art.

As shown in FIG12 , in another embodiment of method 100 , a physician or surgeon performs surgery to access a peripheral vein 30 and connects a pump (directly or via an outflow tube) at step 112 to establish fluid communication with the peripheral vein 30. At step 113 , the pump is fluidically connected to a peripheral artery 221 (directly or via an inflow tube). At step 114 , the pump is operated to pump oxygenated blood from the donor peripheral artery 221 to the recipient peripheral vein 30. At step 115 , pumping continues for a period of time while the physician waits for the total diameter and lumen diameter of the peripheral recipient vein to continue to increase to the desired amount. At step 116 , the blood pump system is removed, and at step 117 , the peripheral recipient vein with the continuously increasing total diameter and lumen diameter is used to form an AVF, AVG, or bypass graft, or other surgical procedures or procedures requiring a vein as determined by one skilled in the art.

As shown in Figure 13, in another embodiment of method 100, at step 118, a physician or surgeon performs surgery to access a peripheral donor artery and uses one or more conduits to establish fluid communication with a recipient site, such as the superior vena cava or the right atrium. At step 119, blood is moved from the donor artery to the recipient site, which can be achieved passively without a pump or actively with the assistance of a pump. At step 120, blood is moved from the donor artery to the recipient site over a period of time while the physician waits for the total diameter and lumen diameter of the peripheral donor artery to continue to increase to the desired amount. At step 121, the conduit is removed. In some embodiments, at step 121, the pump is also removed. At step 122, the peripheral donor artery with continuously increasing total diameter and lumen diameter is used to form an AVF, AVG, or bypass graft, or other surgical procedure or procedure requiring a vein as determined by one skilled in the art.

As shown in Figure 14, in another embodiment of method 100, in step 123, a physician or surgeon performs surgery to fluidically access a recipient site (e.g., superior vena cava or right atrium) in the vascular system and connects a pump (directly or via an inflow conduit) to the recipient site. Then, in step 124, the physician or surgeon establishes fluid communication between a peripheral donor vein and the pump (directly or via an outflow conduit). In step 125, the pump is operated to pump deoxygenated blood from the peripheral donor vein to the recipient site. In step 126, pumping continues for a period of time while the physician waits for the overall diameter and lumen diameter of the peripheral donor vein to continuously increase. In step 127, the pump system is removed, and in step 128, the donor vein with the continuously increasing overall diameter and lumen diameter is used to form an AVF, AVG, or bypass graft, or other surgical procedures or procedures requiring a vein as determined by those skilled in the art.

In various embodiments, the method 100 and/or system 10 can be used for periodic and/or intermittent phases rather than continuous treatment. Typically, hemodialysis treatments, which can last 3 to 5 hours, are provided up to 3 times per week in a dialysis facility. Various embodiments of the system 10 and method 100 can be used to provide blood pumping treatments on a similar schedule over a 4 to 6 week period. These treatments can be performed in any suitable location, including in an outpatient setting.

In one embodiment, blood pumping therapy is intermittently performed in conjunction with hemodialysis therapy. In this embodiment, a low-flow pump, a standard indwelling hemodialysis catheter serving as an inflow catheter, and a minimally invasive needle or catheter placed in a peripheral vein serving as an outflow catheter can be used. Multiple continuous flow blood pumps (e.g., catheter-based VADs and pediatric cardiopulmonary bypass or extracorporeal membrane oxygenation pumps) operated from a bedside console can be readily adapted for use in method 100.

In various embodiments where blood pumping occurs via periodic, intermittent pumping phases, access to the blood vessel may also be achieved via one or more ports or surgically created access sites. By way of example, and not limitation, access for inflow may be achieved via a venous needle, a peripherally inserted central catheter, a tunneled or non-tunneled central catheter, or a percutaneously implantable central catheter with a port, an arterial needle, or an arterial catheter. By way of example, and not limitation, access for outflow may be achieved via a venous needle or a peripheral intravenous catheter.

In another embodiment of system 10, a low flow pump is used to increase the average WSS and average blood velocity in the blood vessel. The low flow pump has an inlet conduit that is fluidically connected to a blood vessel or position (e.g., right atrium) in the cardiovascular system and an outlet conduit that is fluidically connected to a vein, and blood is pumped from the blood vessel or position in the cardiovascular system to the vein for a period of about 7 days and 84 days. The low flow pump pumps blood so that the average wall shear stress of the vein is between about 0.076 Pa and about 23 Pa. The low flow pump also includes an adjustment device. The adjustment device can communicate with an automatic adjustment system based on software, or the adjustment device can have a manual controller. The length of the inlet conduit and the outlet conduit can be about 0.5 centimeters to about 110 centimeters, and has a total length of from 4 to 220 centimeters.

The present invention also relates to a method of assembling and operating a blood pump system, including various embodiments of the pump-tubing system 10. The method includes attaching a first tubing in fluid communication with the pump-tubing system 10 to an artery and attaching a second tubing in fluid communication with the pump-tubing system to a vein. The pump-tubing system 10 is then activated to pump blood between the artery and the vein.

In understanding the scope of the present invention, the term "comprise" and its derivatives, as used herein, are intended to be open-ended terms that indicate the presence of the described features, elements, parts, groups, wholes and/or steps, but do not exclude the presence of other unstated features, elements, parts, groups, wholes and/or steps. The above understanding also applies to words with similar meanings, such as the terms "comprises", "having" and their derivatives. As used herein, terms of degree such as "substantially", "about" and "approximately" mean a reasonable amount of deviation from the modified term so that the end result is not significantly changed. For example, these terms can be understood to include a deviation of at least ±5% of the modified term, as long as this deviation does not offset the meaning of the word it modifies.

Although only selected embodiments have been chosen to describe the present invention, it will be understood by those skilled in the art from this disclosure that various changes and modifications may be made therein without departing from the scope of the invention as defined in the appended claims. For example, the size, shape, position or orientation of the various components may be changed as needed and/or desired. Components shown as being directly connected or in contact with each other may have intermediate structures disposed therebetween. The function of one element may be performed by two, and vice versa. The structure and function of one embodiment may be used in another embodiment. It is not necessary that all advantages be embodied in a particular embodiment at the same time. Each feature that is distinguishable from the prior art, alone or in combination with other features, should also be considered a separate description of further inventions by the applicant, including the structural and/or functional concepts embodied by such features. Thus, the above description of embodiments according to the present invention is provided for illustration only and is not intended to limit the invention as defined in the appended claims and their equivalents.

Claims (52)

1. A system for creating an arteriovenous fistula, arteriovenous graft, or bypass graft by increasing the total diameter and lumen diameter of a donor vessel, the system comprising: A pump configured to pump blood; A first conduit having a first end configured for fluid connection to a donor blood vessel and a second end connected to the inlet of the pump; A second conduit, having a first end configured for fluid connection to a peripheral receptor vein and a second end connected to the outlet of the pump, the second conduit directs blood flow into the peripheral receptor vein; and A control unit, connected to the pump, is configured such that the pump pumps blood into the peripheral recipient vein having a mean pulse pressure of less than 40 mmHg, thereby inducing wall shear stress in the donor vessel of 0.76 Pa to 23 Pa for a period of at least 7 days. The first conduit has a first inlet fluidly connected to the donor blood vessel and a first outlet fluidly connected to the inlet of the pump; the first conduit is used to remove blood from the donor blood vessel. The second conduit has a second outlet fluidly connected to the recipient vein and a second inlet fluidly connected to the outlet of the pump. The second conduit is used to transfer blood into the recipient vein. At least one of the first and second conduits is connected to the blood pump via a connector, the connector including a barbed fitting. 2. The system according to claim 1, wherein the pump pumps blood at a rate between 50 ml/min and 2500 ml/min. 3. The system according to claim 1, wherein when the pump is in operation, the average wall shear stress in the donor blood vessel is between 0.76 Pa and 23 Pa. 4. The system according to claim 1, wherein when the pump is operating, the average velocity of the blood in the donor blood vessel is between 10 cm/s and 100 cm/s. 5. The system according to claim 1, wherein the blood is pumped through the pump for a period of 7 to 84 days. 6. The system according to claim 1, wherein the blood is pumped through the pump for a period of 7 to 42 days. 7. The system according to claim 1, characterized in that, The total diameter or lumen diameter of the donor blood vessel and the blood flow through the donor blood vessel are determined by the control unit; and The control unit changes the speed of the pump portion of the pump in order to maintain a desired mean wall shear stress or a desired mean blood velocity in the peripheral receptor vein. 8. The system according to claim 1, wherein blood is pumped through the pump until the lumen diameter or the total diameter of the donor blood vessel increases from the initial diameter. 9. The system according to claim 1, wherein the peripheral receptor vein is selected from the group consisting of: cephalic vein, ulnar vein, antecubital vein, basilic vein, brachial vein, small saphenous vein, great saphenous vein, or femoral vein. 10. The system according to claim 1, wherein the pumping of blood causes the average blood pressure in the recipient vein to be less than 30 mmHg. 11. The system according to claim 1, wherein the pump is implanted in the patient's body. 12. The system according to claim 1, wherein the pump is held outside the patient's body. 13. The system according to claim 1, wherein the continuously increasing lumen diameter or total diameter of the recipient vein is at least 2.5 mm. 14. The system according to claim 13, wherein the continuously increasing lumen diameter or total diameter of the recipient vein is at least 4.0 mm. 15. The system according to claim 1, wherein the pump is a rotary blood pump. 16. The system according to claim 15, wherein the rotary blood pump is a centrifugal pump. 17. The system according to claim 1, wherein the pump is configured to have at least one contact bearing. 18. The system according to claim 1, wherein the pump is driven by an electric motor. 19. The system according to claim 1, wherein the pumping of blood by the pump is controlled by the control unit, the control unit being configured to control the pump. 20. The system according to claim 19, wherein the parameters of the pump are controlled by the control unit, and the pump parameters include the pump speed, the pump impeller speed, or the pressure in the pipeline. 21. The system according to claim 20, wherein the parameters of the pump are manually adjusted using the control unit. 22. The system according to claim 20, wherein the parameters of the pump are automatically adjusted by using the control unit. 23. The system of claim 20, characterized in that at least one sensor is located in the pump, conduit, or patient's vascular system, the sensor measuring at least one of the following: a) the power or current necessary to operate the pump under certain operating conditions; b) blood velocity; c) blood flow rate; d) resistance to blood flow entering or leaving a peripheral receptor vein; e) blood pressure or pulse pressure in the conduit, outflow conduit, or peripheral receptor vein. 24. The system according to claim 1, wherein the control unit includes a rechargeable power unit for providing power to the pump. 25. The system according to claim 1, wherein at least one of the first conduit and the second conduit is connected to the blood pump using a radial compression connector. 26. The system according to claim 1, wherein at least a portion of the first conduit or the second conduit comprises at least one element selected from polyvinyl chloride, polyethylene, polyurethane and/or silicone. 27. The system according to claim 1, wherein at least a portion of at least one of the first pipe and the second pipe comprises a shape memory alloy, a self-expanding material, or a radially expanding material. 28. The system according to claim 27, wherein the shape memory alloy is nickel-titanium alloy. 29. The system according to claim 28, wherein at least one of the first conduit and the second conduit comprises braided nitinol. 30. The system according to claim 28, wherein at least one of the first conduit and the second conduit comprises a Nitinol coil. 31. The system according to claim 1, wherein at least a portion of the first conduit or the second conduit comprises at least one element selected from PTFE, ePTFE, polyethylene terephthalate, or polyester. 32. The system according to claim 31, wherein the length of the PTFE, ePTFE, polyethylene terephthalate, or polyester segment is less than 5 cm. 33. The system according to claim 1, wherein at least a portion of the first conduit or the second conduit comprises an antimicrobial coating. 34. The system according to claim 1, wherein at least a portion of the lumen of the first conduit or the second conduit comprises an antithrombotic coating. 35. The system according to claim 34, wherein the antithrombotic coating comprises heparin. 36. The system according to claim 1, wherein at least a portion of the blood contact surface of the pump comprises an antithrombotic coating. 37. The system according to claim 36, wherein the antithrombotic coating comprises heparin. 38. The system according to claim 1, wherein at least a portion of the lumen of the first pipe or the second pipe comprises a lubricating coating. 39. The system according to claim 1, wherein at least one of the first conduit and the second conduit includes a radiopaque marker. 40. The system according to claim 1, wherein at least one of the first pipe and the second pipe has an inner diameter of 2 mm to 10 mm. 41. The system according to claim 1, wherein at least one of the first pipe and the second pipe has an inner diameter of 4 mm. 42. The system according to claim 1, wherein the first and second pipes have a combined length of 2cm to 220cm. 43. The system according to claim 1, wherein at least a portion of the first conduit or the second conduit is configured for subcutaneous tunneling. 44. The system according to claim 1, wherein at least a portion of the first pipe or the second pipe can be trimmed to a desired length and attached to the pump. 45. The system of claim 1, wherein a portion of the first conduit or the second conduit is implanted in the patient's body, and a portion of the conduit is outside the body. 46. The system according to claim 43, wherein after tunneling, the envelope is attached to at least one of the first conduit and the second conduit. 47. The system according to claim 1, wherein the top end of the first conduit is placed in the donor blood vessel. 48. The system according to claim 1, wherein the control unit includes a software program that analyzes information from the pump and automatically adjusts pump parameters to take into account the changes in the continuously increasing total diameter and lumen diameter in the donor blood vessel before achieving the desired continuous increase in the total diameter and lumen diameter in the donor blood vessel. 49. The system according to claim 48, wherein the pump parameters are pump speed, impeller revolutions per minute, or outlet pipe pressure. 50. The system according to claim 48, wherein the pump parameters are adjusted periodically. 51. The system according to claim 50, wherein the pump parameters are pump speed or impeller revolutions per minute. 52. The system according to claim 1, characterized in that the pumping of blood causes an increase in the length of the donor blood vessel, and the increase in length is retained after the pumping ends.