Patent Publication Number: US-2005131385-A1

Title: Cannulae for selectively enhancing blood flow

Description:
BACKGROUND OF THE INVENTION  
      1. Field of the Invention  
      This application relates to cannulae and, in particular, to cannulae capable of enhancing blood flow around the cannulae within the vasculature of a patient.  
      2. Description of the Related Art  
      Treatment and diagnosis of a variety of health conditions in a patient can involve withdrawing blood from the patient&#39;s vascular system. For example, a syringe can be inserted into the patient&#39;s vasculature to withdraw blood for testing. It is sometimes necessary to introduce blood or other fluids into a patient&#39;s vasculature, e.g., an injection via an intravenous line, to provide treatment or obtain a diagnosis.  
      Treatment of organ failure can involve coordinated withdrawal and introduction of blood, in connection with some additional treatment. Dialysis, for example, involves withdrawing blood from the vasculature, filtering the blood, and infusing the blood back into the vasculature for further circulation. An emerging treatment for congestive heart failure involves coordinated withdrawal of blood from and infusion of blood into the vasculature without further treatment. Both such treatments sometimes call for the insertion of a cannula into the vasculature of the patient.  
      The size of the cannula employed in these and other vascular treatments can sometimes approach the size of the vessel into which it is inserted. For example, relatively large cannula size may be required where the treatment requires significant amounts of blood to be withdrawn at relatively high flow rates. The desirability of employing multilumen cannulae is another factor that contributes to increased cannula size. Depending on the application, larger cannulae can present a risk to tissue located downstream of where the cannulae are applied. For example, as the size of the cannula to be introduced approaches the size of the blood vessel, blood-flow downstream of the cannula may be restricted. Prolonged restriction of the vessel can lead to ischemia-related pathology.  
     SUMMARY OF THE INVENTION  
      Overcoming many if not all of the limitations of the prior art, the present invention, in one embodiment, provides a perfusion cannula system for directing blood through the vasculature of a patient. The cannula system includes a cannula body that comprises a proximal end, a distal end, and at least one lumen extending therebetween. The cannula system also includes a balloon and a means for deploying the balloon within the vasculature. The balloon is located on an exterior surface of the cannula body. The cannula system provides space between a vessel wall and the cannula body when the cannula body resides within the patient to permit blood flow past the cannula body.  
      In another embodiment, a perfusion cannula system for directing blood through the vasculature of a patient comprises means for creating space around the cannula body within the vasculature to permit blood flow past the cannula.  
      In another embodiment, a perfusion system for directing blood through the vasculature of a patient comprises a multilumen cannula. A plurality of radially spaced balloons are configured to be selectively inflated while residing with the vasculature to create space around the cannula within the vasculature to permit blood flow past the cannula.  
      In an additional embodiment, a perfusion cannula system comprises a cannula body having an aperture formed therein in fluid communication with a lumen. A sleeve is carried by the cannula and is configured to be moveable relative to the aperture to selectively cover and uncover the aperture as desired.  
      In another embodiment, a perfusion cannula system comprises means for enhancing blood flow past the cannula when the cannula body resides within the patient.  
      In another embodiment, an extracardiac heart assist system comprises a pump that has an inlet and an outlet. An inflow conduit is coupled with the inlet. An outflow conduit is coupled with the outlet. An intravascular conduit is configured to provide fluid communication between the vasculature of a patient and at least one of the inflow conduit and the outflow conduit. The intravascular conduit has a proximal end, a distal end, at least one lumen extending therebetween, and a means for selectively enhancing blood flow past the cannula when the cannula resides within the patient.  
      In another embodiment, a method of treating a patient using an extracardiac heart assist system comprises the steps of: inserting a cannula system into the vasculature of a patient, the cannula system being actuatable to enhance blood flow past the cannula when the cannula resides in the vasculature of the patient; and selectively actuating the cannula system, whereby blood flow past the cannula is enhanced. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
      These and other features and advantages of the invention will now be described with reference to the drawings, which are intended to illustrate and not to limit the invention.  
       FIG. 1  is a schematic view of one embodiment of a heart assist system having multiple conduits for multi-site application, shown applied to a patient&#39;s vascular system;  
       FIG. 2  is a schematic view of another application of the embodiment of  FIG. 1 ;  
       FIG. 3  is a schematic view of another embodiment of a heart assist system having multiple conduits for multi-site application wherein each of the conduits is applied to more than one vessel, shown applied to a patient&#39;s vascular system;  
       FIG. 4  is a schematic view of another embodiment of a heart assist system having multiple conduits for multi-site application and employing a connector with a T-shaped fitting, shown applied to a patient&#39;s vascular system;  
       FIG. 5  is a schematic view of an L-shaped connector coupled with an inflow conduit, shown inserted within a blood vessel;  
       FIG. 6  is a schematic view of another embodiment of a heart assist system having multiple conduits for multi-site application, shown applied to a patient&#39;s vascular system;  
       FIG. 7  is a schematic view of another application of the embodiment of  FIG. 6 , shown applied to a patient&#39;s vascular system;  
       FIG. 8  is a schematic view of another application of the embodiment of  FIG. 6 , shown applied to a patient&#39;s vascular system;  
       FIG. 9  is a schematic view of another embodiment of a heart assist system having multiple conduits for multi-site application, a reservoir, and a portable housing for carrying a portion of the system directly on the patient;  
       FIG. 10  is a schematic view of another embodiment of a heart assist system having a multilumen cannula for single-site application, shown applied to a patient&#39;s vascular system;  
       FIG. 11  is a schematic view of a modified embodiment of the heart assist system of  FIG. 10 , shown applied to a patient&#39;s vascular system;  
       FIG. 12  is a schematic view of another embodiment of a heart assist system having multiple conduits for single-site application, shown applied to a patient&#39;s circulatory system;  
       FIG. 13  is a schematic view of another application of the embodiment of  FIG. 12 , shown applied to a patient&#39;s vascular system;  
       FIG. 14  is a schematic view of one application of an embodiment of a heart assist system having an intravascular pump enclosed in a protective housing, wherein the intravascular pump is inserted into the patient&#39;s vasculature through a non-primary vessel;  
       FIG. 15  is a schematic view of another embodiment of a heart assist system having an intravascular pump housed within a conduit having an inlet and an outlet, wherein the intravascular pump is inserted into the patient&#39;s vasculature through a non-primary vessel;  
       FIG. 16  is a schematic view of a modified embodiment of the heart assist system of  FIG. 15  in which an additional conduit is shown adjacent the conduit housing the pump, and in which the pump comprises a shaft-mounted helical thread;  
       FIG. 17  is a schematic view of one embodiment of a perfusion cannula system;  
       FIG. 18  is a schematic view of another embodiment of a perfusion cannula system;  
       FIG. 19  is a schematic view of another embodiment of a perfusion cannula system;  
       FIG. 20  is a schematic view of an application to a patient of a heart assist system including a perfusion cannula system according to the embodiment shown in  FIG. 17 ;  
       FIG. 21  is an enlarged schematic view of a portion of  FIG. 20 , showing how space may be created by the embodiment shown in  FIG. 17 ;  
       FIG. 22  is a cross-sectional view of taken along the section plane  22 - 22  shown in  FIG. 21 ;  
       FIG. 23  is an enlarged schematic view similar to that of  FIG. 21 , showing how space may be created by the embodiment shown in  FIG. 18 ;  
       FIG. 24  is a cross-sectional view of taken along the section plane  24 - 24  shown in  FIG. 23 ;  
       FIG. 25  is an enlarged schematic view similar to that of  FIG. 21  of the embodiment shown in  FIG. 19 , which is shown in a first configuration; and  
       FIG. 26  is an enlarged schematic view showing how space may be created by the embodiment shown in  FIG. 19  when in a second configuration. 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT  
      Turning now to the drawings provided herein, more detailed descriptions of various embodiments of heart assist systems and cannulae for use therewith are provided below.  
     I. Extracardiac Heart Assist Systems and Methods  
      A variety of cannulae are described herein that can be used in connection with a variety of heart assist systems that supplement blood perfusion. Such systems preferably are extracardiac in nature. In other words, the systems supplement blood perfusion, without the need to interface directly with the heart and aorta. Thus, the systems can be applied without major invasive surgery. The systems also lessen the hemodynamic burden or workload on the heart by reducing afterload, impedence, and/or left ventricular end diastolic pressure and volume (preload). The systems also advantageously increase peripheral organ perfusion and provide improvement in neurohormonal status. As discussed more fully below, the systems can be applied using one or more cannulae, one or more vascular grafts, and a combination of one or more cannulae and one or more vascular grafts. For systems employing cannula(e), the cannula(e) can be applied through multiple percutaneous insertion sites (sometimes referred to herein as a multi-site application) or through a single percutaneous insertion site (sometimes referred to herein as a single-site application).  
      A. Heart Assist Systems and Methods Employing Multi-Site Application  
      With reference to  FIG. 1 , a first embodiment of a heart assist system  10  is shown applied to a patient  12  having an ailing heart  14  and an aorta  16 , from which peripheral brachiocephalic blood vessels extend, including the right subclavian artery  18 , the right carotid artery  20 , the left carotid artery  22 , and the left subclavian artery  24 . Extending from the descending aorta is another set of peripheral blood vessels, the left and right iliac arteries which transition into the left and right femoral arteries  26 ,  28 , respectively. As is known, each of the arteries  16 ,  18 ,  20 ,  22 ,  24 ,  26 , and  28  generally conveys blood away from the heart. The vasculature includes a venous system that generally conveys blood to the heart. As will be discussed in more detail below, the heart assist systems described herein can also be applied to non-primary veins, including the left femoral vein  30 .  
      The heart assist system  10  comprises a pump  32 , having an inlet  34  and an outlet  36  for connection of conduits thereto. The pump  32  preferably is a rotary pump, either an axial type or a centrifugal type, although other types of pumps may be used, whether commercially-available or customized. The pump  32  preferably is sufficiently small to be implanted subcutaneously and preferably extrathoracically, for example in the groin area of the patient  12 , without the need for major invasive surgery. Because the heart assist system  10  is an extracardiac system, no valves are necessary. Any inadvertent backflow through the pump  32  and/or through the inflow conduit would not harm the patient  12 .  
      Regardless of the style or nature chosen, the pump  32  is sized to generate blood flow at subcardiac volumetric rates, less than about 50% of the flow rate of an average healthy heart, although flow rates above that may be effective. Thus, the pump  32  is sized and configured to discharge blood at volumetric flow rates anywhere in the range of 0.1 to 3 liters per minute, depending upon the application desired and/or the degree of need for heart assist. For example, for a patient experiencing advanced congestive heart failure, it may be preferable to employ a pump that has an average subcardiac rate of 2.5 to 3 liters per minute. In other patients, particularly those with minimal levels of heart failure, it may be preferable to employ a pump that has an average subcardiac rate of 0.5 liters per minute or less. In yet other patients it may be preferable to employ a pump that is a pressure wave generator that uses pressure to augment the flow of blood generated by the heart.  
      In one embodiment, the pump  32  is a continuous flow pump, which superimposes continuous blood-flow on the pulsatile aortic blood-flow. In another embodiment, the pump  32  has the capability of synchronous actuation; i.e., it may be actuated in a pulsatile mode, either in copulsating or counterpulsating fashion.  
      For copulsating action, it is contemplated that the pump  32  would be actuated to discharge blood generally during systole, beginning actuation, for example, during isovolumic contraction before the aortic valve opens or as the aortic valve opens. The pump  32  would be static while the aortic valve is closed following systole, ceasing actuation, for example, when the aortic valve closes.  
      For counterpulsating actuation, it is contemplated that the pump  32  would be actuated generally during diastole, ceasing actuation, for example, before or during isovolumic contraction. Such an application would permit and/or enhance coronary blood perfusion. In this application, it is contemplated that the pump  32  would be static during the balance of systole after the aortic valve is opened, to lessen the burden against which the heart must pump. The aortic valve being open encompasses the periods of opening and closing, wherein blood is flowing therethrough.  
      It should be recognized that the designations copulsating and counterpulsating are general identifiers and are not limited to specific points in the patient&#39;s heart cycle when the pump  32  begins and discontinues actuation. Rather, they are intended to generally refer to pump actuation in which the pump  32  is actuating, at least in part, during systole and diastole, respectively. For example, it is contemplated that the pump  32  might be activated to be out of phase from true copulsating or counterpulsating actuation described herein, and still be synchronous, depending upon the specific needs of the patient or the desired outcome. One might shift actuation of the pump  32  to begin prior to or after isovolumic contraction or to begin before or after isovolumic relaxation.  
      Furthermore, the pulsatile pump may be actuated to pulsate asynchronously with the patient&#39;s heart. Typically, where the patient&#39;s heart is beating irregularly, there may be a desire to pulsate the pump  32  asynchronously so that the perfusion of blood by the heart assist system  10  is more regular and, thus, more effective at oxygenating the organs. Where the patient&#39;s heart beats regularly, but weakly, synchronous pulsation of the pump  32  may be preferred.  
      The pump  32  is driven by a motor  40  and/or other type of drive means and is controlled preferably by a programmable controller  42  that is capable of actuating the pump  32  in pulsatile fashion, where desired, and also of controlling the speed or output of the pump  32 . For synchronous control, the patient&#39;s heart would preferably be monitored with an EKG in which feedback would be provided the controller  42 . The controller  42  is preferably programmed by the use of external means. This may be accomplished, for example, using RF telemetry circuits of the type commonly used within implantable pacemakers and defibrillators. The controller may also be autoregulating to permit automatic regulation of the speed, and/or regulation of the synchronous or asynchronous pulsation of the pump  32 , based upon feedback from ambient sensors monitoring parameters, such as pressure or the patient&#39;s EKG. It is also contemplated that a reverse-direction pump be utilized, if desired, in which the controller is capable of reversing the direction of either the drive means or the impellers of the pump. Such a pump might be used where it is desirable to have the option of reversing the direction of circulation between two blood vessels.  
      Power to the motor  40  and the controller  42  may be provided by a power source  44 , such as a battery, that is preferably rechargeable by an external induction source (not shown), such as an RF induction coil that may be electromagnetically coupled to the battery to induce a charge therein. Alternative power sources are also possible, including a device that draws energy directly from the patient&#39;s body; e. g., the patient&#39;s muscles, chemicals or heat. The pump can be temporarily stopped during recharging with no appreciable life threatening effect, because the system only supplements the heart, rather than substituting for the heart.  
      While the controller  42  and power source  44  are preferably pre-assembled to the pump  32  and implanted therewith, it is also contemplated that the pump  32  and motor  40  be implanted at one location and the controller  42  and the power source  44  be implanted in a separate location. In one alternative arrangement, the pump  32  may be driven externally through a percutaneous drive line or cable, as shown in  FIG. 16 . In another variation, the pump, motor and controller may be implanted and powered by an extracorporeal power source. In the latter case, the power source could be attached to the side of the patient to permit fully ambulatory movement.  
      The inlet  34  of the pump  32  is preferably connected to an inflow conduit  50  and an outflow conduit  52  to direct blood flow from one peripheral blood vessel to another. The conduits  50 ,  52  preferably are flexible conduits, as discussed more fully below. The conduits  50 ,  52  are coupled with the peripheral vessels in different ways in various embodiments of the heart assist system  10 . As discussed more fully below, at least one of the conduits  50 ,  52  can be connected to a peripheral vessel, e.g., as a graft, using an anastomosis connection, and at least one of the conduits  50 ,  52  can be coupled with the same or another vessel via insertion of a cannula into the vasculature. Also, more than two conduits are used in some embodiments, as discussed below.  
      The inflow and outflow conduits  50 ,  52  may be formed from Dacron, Hemashield, Gortex, PVC, polyurethane, PTFE, ePTFE, nylon, or PEBAX materials, although other synthetic materials may be suitable. The inflow and outflow conduits  50 ,  52  may also comprise biologic materials or pseudobiological (hybrid) materials (e.g., biologic tissue supported on a synthetic scaffold). The inflow and outflow conduits  50 ,  52  are preferably configured to minimize kinks so blood flow is not meaningfully interrupted by normal movements of the patient or compressed easily from external forces. In some cases, the inflow and/or outflow conduits  50 ,  52  may come commercially already attached to the pump  32 . Where it is desired to implant the pump  32  and the conduits  50 ,  52 , it is preferable that the inner diameter of the conduits  50 ,  52  be less than 25 mm, although diameters slightly larger may be effective.  
      In one preferred application, the heart assist system  10  is applied in an arterial-arterial fashion; for example, as a femoral-axillary connection, as is shown in  FIG. 1 . It should be appreciated by one of ordinary skill in the art that an axillary-femoral connection would also be effective using the embodiments described herein. Indeed, it should be recognized by one of ordinary skill in the art that the present invention might be applied to any of the peripheral blood vessels in the patient. Another application of the heart assist system  10  couples the conduits  50 ,  52  with the same non-primary vessel in a manner similar to the application shown in  FIG. 8  and discussed below.  
       FIG. 1  shows that the inflow conduit  50  has a first end  56  that connects with the inlet  34  of the pump  32  and a second end  58  that is coupled with a first non-primary blood vessel (e.g., the left femoral artery  26 ) by way of an inflow cannula  60 . The inflow cannula  60  has a first end  62  and a second end  64 . The first end  62  is sealably connected to the second end  58  of the inflow conduit  50 . The second end  64  is inserted into the blood vessel (e.g., the left femoral artery  26 ). Although shown as discrete structures in  FIG. 1 , one skilled in the art would recognize that the inflow conduit  50  and the cannula  60  may be unitary in construction. The cannula  60  may take any suitable form, e.g., including one or more of the features of the cannulae discussed below in connection with  FIGS. 17-26 .  
      Where the conduit  50  is at least partially extracorporeal, the inflow cannula  60  also may be inserted through a surgical opening (e.g., as shown in  FIG. 6  and described in connection therewith) or percutaneously, with or without an introducer sheath (not shown). In other applications, the inflow cannula  60  could be inserted into the right femoral artery or any other peripheral artery.  
       FIG. 1  shows that the outflow conduit  52  has a first end  66  that connects to the outlet  36  of the pump  32  and a second end  68  that connects with a second peripheral blood vessel, preferably the left subclavian artery  24  of the patient  12 , although the right axillary artery, or any other peripheral artery, would be acceptable. In one application, the connection between the outflow conduit  52  and the second blood vessel is via an end-to-side anastomosis, although a side-to-side anastomosis connection might be used mid-stream of the conduit where the outflow conduit were connected at its second end to yet another blood vessel or at another location on the same blood vessel (neither shown). Preferably, the outflow conduit  52  is attached to the second blood vessel at an angle that results in the predominant flow of blood out of the pump  32  proximally toward the aorta  16  and the heart  14 , such as is shown in  FIG. 1 , while still maintaining sufficient flow distally toward the hand to prevent limb ischemia.  
      In another embodiment, the inflow conduit  50  is connected to the first blood vessel via an end-to-side anastomosis, rather than via the inflow cannula  60 . The inflow conduit  50  could also be coupled with the first blood vessel via a side-to-side anastomosis connection mid-stream of the conduit where the inflow conduit were connected at its second end to an additional blood vessel or at another location on the same blood vessel (neither shown). Further details of these arrangements and other related applications are described in U.S. application Ser. No. 10/289,467, filed Nov. 6, 2002, the entire contents of which is hereby incorporated by reference in its entirety and made a part of this specification.  
      In another embodiment, the outflow conduit  52  also is coupled with the second blood vessel via a cannula, as shown in  FIG. 6 . This connection may be achieved in a manner similar to that shown in  FIG. 1  in connection with the first blood vessel.  
      It is preferred that application of the heart assist system  10  to the peripheral or non-primary blood vessels be accomplished subcutaneously; e.g., at a shallow depth just below the skin or first muscle layer so as to avoid major invasive surgery. It is also preferred that the heart assist system  10  be applied extrathoracically to avoid the need to invade the patient&#39;s chest cavity. Where desired, the entire heart assist system  10  may be implanted within the patient  12 , either extravascularly, e.g., as in  FIG. 1 , or at least partially intravascularly, e.g., as in  FIGS. 14-16 .  
      In the case of an extravascular application, the pump  32  may be implanted, for example, into the groin area, with the inflow conduit  50  fluidly connected subcutaneously to, for example, the femoral artery  26  proximate the pump  32 . The outflow conduit would be tunneled subcutaneously through to, for example, the left subclavian artery  24 . In an alternative arrangement, the pump  32  and associated drive and controller could be temporarily fastened to the exterior skin of the patient, with the inflow and outflow conduits  50 ,  52  connected percutaneously. In either case, the patient may be ambulatory without restriction of tethered lines.  
      While the heart assist system  10  and other heart assist systems described herein may be applied to create an arterial-arterial flow path, given the nature of the heart assist systems, i.e., supplementation of circulation to meet organ demand, a venous-arterial flow path may also be used. For example, with reference to  FIG. 2 , one application of the heart assist system  10  couples the inflow conduit  50  with a non-primary vein of the patient  12 , such as the left femoral vein  30 . In this arrangement, the outflow conduit  50  may be fluidly coupled with one of the peripheral arteries, such as the left subclavian artery  24 . Arterial-venous arrangements are contemplated as well. In those venous-arterial cases where the inflow is connected to a vein and the outflow is connected to an artery, the pump  32  should be sized to permit flow sufficiently small so that oxygen-deficient blood does not rise to unacceptable levels in the arteries. It should be appreciated that the connections to the non-primary veins could be by one or more approach described above for connecting to a non-primary artery. It should also be appreciated that the present invention could be applied as a venous-venous flow path, wherein the inflow and outflow are connected to separate peripheral veins. In addition, an alternative embodiment comprises two discrete pumps and conduit arrangements, one being applied as a venous-venous flow path, and the other as an arterial-arterial flow path.  
      When venous blood is mixed with arterial blood either at the inlet of the pump or the outlet of the pump the ratio of venous blood to arterial blood should be controlled to maintain an arterial saturation of a minimum of 80% at the pump inlet or outlet. Arterial saturation can be measured and/or monitored by pulse oximetry, laser doppler, colorimetry or other methods used to monitor blood oxygen saturation. The venous blood flow into the system can then be controlled by regulating the amount of blood allowed to pass through the conduit from the venous-side connection.  
       FIG. 3  shows another embodiment of a heart assist system  110  applied to the patient  12 . For example, the heart assist system  110  includes a pump  132  in fluid communication with a plurality of inflow conduits  150 A,  150 B and a plurality of outflow conduits  152 A,  152 B. Each pair of conduits converges at a generally Y-shaped convergence  196  that converges the flow at the inflow end and diverges the flow at the outflow end. Each conduit may be connected to a separate peripheral blood vessel, although it is possible to have two connections to the same blood vessel at remote locations. In one arrangement, all four conduits are connected to peripheral arteries. In another arrangement, one or more of the conduits could be connected to veins. In the arrangement of  FIG. 3 , the inflow conduit  150 A is connected to the left femoral artery  26  while the inflow conduit  150 B is connected to the left femoral vein  30 . The outflow conduit  152 A is connected to the left subclavian artery  24  while the outflow conduit  152 B is connected to the left carotid artery  22 . Preferably at least one of the conduits  150 A,  150 B,  152 A, and  152 B is coupled with a corresponding vessel via a cannula. In the illustrated embodiment, the inflow conduit  150 B is coupled with the left femoral vein  30  via a cannula  160 . The cannula  160  is coupled in a manner similar to that shown in  FIG. 2  and described in connection with the cannula  60 . The cannula  160  preferably takes any suitable form, e.g., including one or more of the features of the cannulae discussed below in connection with  FIGS. 17-26 .  
      The connections of any or all of the conduits of the system  110  to the blood vessels may be via an anastomosis connection or via a connector, as described below in connection with  FIG. 4 . In addition, the embodiment of  FIG. 3  may be applied to any combination of peripheral blood vessels that would best suit the patient&#39;s condition. For example, it may be desired to have one inflow conduit and two outflow conduits or vice versa. It should be noted that more than two conduits may be used on the inflow or outflow side, where the number of inflow conduits is not necessarily equal to the number of outflow conduits.  
      It is contemplated that, where an anastomosis connection is not desired, a connector may be used to connect at least one of the inflow conduit and the outflow conduit to a peripheral blood vessel. With reference to  FIG. 4 , an embodiment of a heart assist system  210  is shown, wherein an outflow conduit  252  is connected to a non-primary blood vessel, e.g., the left subclavian artery  24 , via a connector  268  that comprises a three-opening fitting. In one embodiment, the connector  268  comprises an intra-vascular, generally T-shaped fitting  270  having a proximal end  272  (with respect to the flow of blood in the left axillary artery and therethrough), a distal end  274 , and an angled divergence  276  permitting connection to the outflow conduit  252  and the left subclavian artery  24 . The proximal and distal ends  274 ,  276  of the fittings  272  permit connection to the blood vessel into which the fitting is positioned, e.g., the left subclavian artery  24 . The angle of divergence  276  of the fittings  272  may be 90 degrees or less in either direction from the axis of flow through the blood vessel, as optimally selected to generate the needed flow distally toward the hand to prevent limb ischemia, and to insure sufficient flow and pressure toward the aorta to provide the circulatory assistance and workload reduction needed while minimizing or avoiding endothelial damage to the blood vessel. In another embodiment, the connector  268  is a sleeve (not shown) that surrounds and attaches to the outside of the non-primary blood vessel where, within the interior of the sleeve, a port to the blood vessel is provided to permit blood flow from the outflow conduit  252  when the conduit  252  is connected to the connector  268 .  
      Other types of connectors having other configurations are contemplated that may avoid the need for an anastomosis connection or that permit connection of the conduit(s) to the blood vessel(s). For example, it is contemplated that an L-shaped connector be used if it is desired to withdraw blood more predominantly from one direction of a peripheral vessel or to direct blood more predominantly into a peripheral vessel. Referring to  FIG. 5 , the inflow conduit  250  is fluidly connected to a peripheral vessel, for example, the left femoral artery  26 , using an L-shaped connector  278 . Of course the system  210  could be configured so that the outflow conduit  252  is coupled to a non-primary vessel via the L-shaped connector  278  and the inflow conduit  250  is coupled via a cannula, as shown in  FIG. 3 . The L-shaped connector  278  has an inlet port  280  at a proximal end and an outlet port  282  through which blood flows into the inflow conduit  250 . The L-shaped connector  278  also has an arrangement of holes  284  within a wall positioned at a distal end opposite the inlet port  280  so that some of the flow drawn into the L-shaped connector  278  is diverted through the holes  284 , particularly downstream of the L-shaped connector  278 , as in this application. A single hole  284  in the wall could also be effective, depending upon size and placement. The L-shaped connector  278  may be a deformable L-shaped catheter percutaneously applied to the blood vessel or, in an alternative embodiment, be connected directly to the walls of the blood vessel for more long term application. By directing some blood flow downstream of the L-shaped connector  278  during withdrawal of blood from the vessel, ischemic damage downstream from the connector may be avoided. Such ischemic damage might otherwise occur if the majority of the blood flowing into the L-shaped connector  278  were diverted from the blood vessel into the inflow conduit  252 . It is also contemplated that a connection to the blood vessels might be made via a cannula, wherein the cannula is implanted, along with the inflow and outflow conduits.  
      One advantage of discrete connectors manifests in their application to patients with chronic CHF. A connector eliminates a need for an anastomosis connection between the conduits  250 ,  252  and the peripheral blood vessels where it is desired to remove and/or replace the system more than one time. The connectors could be applied to the first and second blood vessels semi-permanently, with an end cap applied to the divergence for later quick-connection of the present invention system to the patient. In this regard, a patient might experience the benefit of the heart assist systems described herein periodically, without having to reconnect and redisconnect the conduits  250 ,  252  from the blood vessels via an anastomosis procedure each time. Each time it is desired to implement any of the embodiments of the heart assist system, the end caps would be removed and a conduit attached to the connector(s) quickly.  
      In the preferred embodiment of the connector  268 , the divergence  276  is oriented at an acute angle significantly less than 90 degrees from the axis of the T-shaped fitting  270 , as shown in  FIG. 4 , so that a majority of the blood flowing through the outflow conduit  252  into the blood vessel (e.g., left subclavian artery  24 ) flows in a direction proximally toward the heart  14 , rather than in the distal direction. In an alternative embodiment, the proximal end  272  of the T-shaped fitting  270  may have a diameter larger than the diameter of the distal end  274 , without need of having an angled divergence, to achieve the same result.  
      With or without a connector, with blood flow directed proximally toward the aorta  16 , the result may be concurrent flow down the descending aorta, which will result in the reduction of afterload, impedence, and/or reducing left ventricular end diastolic pressure and volume (preload). Thus, the heart assist systems described herein may be applied so to reduce the afterload on the patient&#39;s heart, permitting at least partial if not complete CHF recovery, while supplementing blood circulation. Concurrent flow depends upon the phase of operation of the pulsatile pump and the choice of second blood vessel to which the outflow conduit is connected.  
      A partial external application of the heart assist systems is contemplated where a patient with heart failure is suffering an acute decompensation episode; i.e., is not expected to last long, or in the earlier stages of heart failure (where the patient is in New York Heart Association Classification (NYHAC) functional classes II or III). With reference to  FIGS. 6 and 7 , another embodiment of a heart assist system  310  is applied percutaneously to a patient  312  to connect two non-primary blood vessels wherein a pump  332  and its associated driving means and controls are employed extracorporeally. The pump  332  has an inflow conduit  350  and an outflow conduit  352  associated therewith for connection to two non-primary blood vessels. The inflow conduit  350  has a first end  356  and a second end  358  wherein the second end  358  is connected to a first non-primary blood vessel (e.g., femoral artery  26 ) by way of an inflow cannula  380 . The inflow cannula  380  has a first end  382  sealably connected to the second end  358  of the inflow conduit  350 . The inflow cannula  380  also has a second end  384  that is inserted through a surgical opening  386  or an introducer sheath (not shown) and into the blood vessel (e.g., the left femoral artery  26 ).  
      Similarly, the outflow conduit  352  has a first end  362  and a second end  364  wherein the second end  364  is connected to a second non-primary blood vessel (e.g., the left subclavian artery  24 , as shown in  FIG. 6 , or the right femoral artery  28 , as shown in  FIG. 7 ) by way of an outflow cannula  388 . Like the inflow cannula  380 , the outflow cannula  388  has a first end  390  sealably connected to the second end  364  of the outflow conduit  352 . The outflow cannula  388  also has a second end  392  that is inserted through surgical opening  394  or an introducer sheath (not shown) and into the second blood vessel (e.g., the left subclavian artery  24  or the right femoral artery  28 ). The cannulae  380  and  388  preferably take any suitable form. The cannulae  380 ,  388  may take any suitable form, e.g., including one or more of the features of the cannulae discussed below in connection with  FIGS. 17-26 .  
      As shown in  FIG. 7 , the second end  392  of the outflow cannula  388  may extend well into the aorta  16  of the patient  12 , for example, proximal to the left subclavian artery. If desired, it may also terminate within the left subclavian artery or the left axillary artery, or in other blood vessels, such as the mesenteric or renal arteries (not shown), where in either case, the outflow cannula  388  has passed through at least a portion of a primary artery (in this case, the aorta  16 ). Also, if desired, blood drawn into the extracardiac system  310  described herein may originate from the descending aorta (or an artery branching therefrom) and be directed into a blood vessel that is neither the aorta nor pulmonary artery. By use of a percutaneous application, the heart assist system  310  may be applied temporarily without the need to implant any aspect thereof or to make anastomosis connections to the blood vessels.  
      An alternative variation of the embodiment of  FIG. 6  may be used where it is desired to treat a patient periodically, but for short periods of time each occasion and without the use of special connectors. With this variation, it is contemplated that the second ends of the inflow and outflow conduits  350 ,  352  be more permanently connected to the associated blood vessels via, for example, an anastomosis connection, wherein a portion of each conduit proximate to the blood vessel connection is implanted percutaneously with a removable cap enclosing the externally-exposed first end (or an intervening end thereof) of the conduit external to the patient. When it is desired to provide a circulatory flow path to supplement blood flow, the removable cap on each exposed percutaneously-positioned conduit could be removed and the pump (or the pump with a length of inflow and/or outflow conduit attached thereto) inserted between the exposed percutaneous conduits. In this regard, a patient may experience the benefit of the present invention periodically, without having to reconnect and redisconnect the conduits from the blood vessels each time.  
      Specific methods of applying this alternative embodiment may further comprise coupling the inflow conduit  352  upstream of the outflow conduit  350  (as shown in  FIG. 8 ), although the reverse arrangement is also contemplated. It is also contemplated that either the cannula  380  coupled with the inflow conduit  350  or the cannula  388  coupled with the outflow conduit  352  may extend through the non-primary blood vessel to a second blood vessel (e.g., through the left femoral artery  26  to the aorta  16  proximate the renal branch) so that blood may be directed from-the non-primary blood vessel to the second blood vessel or vice versa.  
      It is contemplated that a means for minimizing the loss of thermal energy in the patient&#39;s blood be provided where any of the heart assist systems described herein are applied extracorporeally. Such means for minimizing the loss of thermal energy may comprise, for example, a heated bath through which the inflow and outflow conduits pass or, alternatively, thermal elements secured to the exterior of the inflow and outflow conduits. Referring to  FIG. 9 , one embodiment comprises an insulating wrap  396  surrounding the outflow conduit  352  having one or more thermal elements passing therethrough. The elements may be powered, for example, by a battery (not shown). One advantage of thermal elements is that the patient may be ambulatory, if desired. Other means that are known by persons of ordinary skill in the art for ensuring that the temperature of the patient&#39;s blood remains at acceptable levels while travelling extracorporeally are also contemplated.  
      If desired, the present inventive system may further comprise a reservoir that is either contained within or in fluid communication with the inflow conduit. This reservoir is preferably made of materials that are nonthrombogenic. Referring to  FIG. 9 , a reservoir  398  is positioned fluidly in line with the inflow conduit  350 . The reservoir  398  serves to sustain adequate blood in the system when the pump demand exceeds momentarily the volume of blood available in the peripheral blood vessel in which the inflow conduit resides until the pump output can be adjusted. The reservoir  398  reduces the risk of excessive drainage of blood from the peripheral blood vessel, which may occur when cardiac output falls farther than the already diminished baseline level of cardiac output, or when there is systemic vasodilation, as can occur, for example, with septic shock. It is contemplated that the reservoir  398  would be primed with an acceptable solution, such as saline, when the present system is first applied to the patient.  
      As explained above, one of the advantages of several embodiments of the heart assist system is that such systems permit the patient to be ambulatory. If desired, the systems may be designed portably so that it may be carried directly on the patient. Referring to  FIG. 9 , this may be accomplished through the use of a portable case  400  with a belt strap  402  to house the pump, power supply and/or the controller, along with certain portions of the inflow and/or outflow conduits, if necessary. It may also be accomplished with a shoulder strap or other techniques, such as a backpack or a fanny pack, that permit effective portability. As shown in  FIG. 9 , blood is drawn through the inflow conduit  350  into a pump contained within the portable case  400 , where it is discharged into the outflow conduit  352  back into the patient.  
      B. Heart Assist Systems and Methods Employing Single-Site Application  
      As discussed above, heart assist systems can be applied to a patient through a single cannulation site. Such single-site systems can be configured with a pump located outside the vasculature of a patient, e.g., as extravascular pumping systems, inside the vasculature of the patient, e.g., as intravascular systems, or a hybrid thereof, e.g., partially inside and partially outside the vasculature of the patient.  
      1. Single-Site Application of Extravascular Pumping Systems  
       FIGS. 10 and 11  illustrate extracardiac heart assist systems that employ an extravascular pump and that can be applied through as a single-site system.  FIG. 10  shows a system  410  that is applied to a patient  12  through a single cannulation site  414  while inflow and outflow conduits fluidly communicate with non-primary vessels. The heart assist system  410  is applied to the patient  12  percutaneously through a single site to couple two blood vessels with a pump  432 . The pump  432  can have any of the features described in connection the pump  32 . The pump  432  has an inflow conduit  450  and an outflow conduit  452  associated therewith. The inflow conduit  450  has a first end  456  and a second end  458 . The first end  456  of the inflow conduit  450  is connected to the inlet of the pump  432  and the second end  458  of the inflow conduit  450  is fluidly coupled with a first non-primary blood vessel (e.g., the femoral artery  26 ) by way of a multilumen cannula  460 . Similarly, the outflow conduit  452  has a first end  462  and a second end  464 . The first end  462  of the outflow conduit  452  is connected to the outlet of the pump  432  and the second end  464  of the outflow conduit  452  is fluidly coupled with a second blood vessel (e.g., the descending aorta  16 ) by way of the multilumen cannula  460 .  
      In one embodiment, the multilumen cannula  460  includes a first lumen  466  and a second lumen  468 . The first lumen  466  extends from a proximal end  470  of the multilumen cannula  460  to a first distal end  472 . The second lumen  468  extends from the proximal end  470  to a second distal end  474 . In the illustrated embodiment, the second end  458  of the inflow conduit  450  is connected to the first lumen  466  of the multilumen cannula  460  and the second end  464  of the outflow conduit  452  is connected to the second lumen  468  of the multilumen cannula  460 .  
      Where there is a desire for the patient  12  to be ambulatory, the multilumen cannula  460  preferably is made of material sufficiently flexible and resilient to permit the patient  12  to be comfortably move about while the multilumen cannula  460  is indwelling in the patient&#39;s blood vessels without causing any vascular trauma.  
      The application shown in  FIG. 10  and described above results in flow from the first distal end  472  to the second distal end  474 . Of course, the flow direction may be reversed using the same arrangement, resulting in flow from the distal end  474  to the distal end  472 . In some applications, the system  410  is applied in an arterial-arterial fashion. For example, as illustrated, the multilumen cannula  460  can be inserted into the left femoral artery  26  of the patient  12  and guided superiorly through the descending aorta to one of numerous locations. In one application, the multilumen cannula  460  can be advanced until the distal end  474  is located in the aortic arch  476  of the patient  12 . The blood could discharge, for example, directly into the descending aorta proximate an arterial branch, such as the left subclavian artery or directly into the peripheral mesenteric artery (not shown).  
      The pump  432  draws blood from the patient&#39;s vascular system in the area near the distal end  472  and into the lumen  466 . This blood is further drawn into the lumen of the conduit  450  and into the pump  432 . The pump  432  then expels the blood into the lumen of the outflow conduit  452 , which carries the blood into the lumen  468  of the multilumen cannula  460  and back into the patient&#39;s vascular system in the area near the distal end  474 .  
       FIG. 11  shows another embodiment of a heart assist system  482  that is similar to the heart assist system  410 , except as set forth below. The system  482  employs a multilumen cannula  484 . In one application, the multilumen cannula  484  is inserted into the left femoral artery  26  and guided superiorly through the descending aorta to one of numerous locations. Preferably, the multilumen cannula  484  has an inflow port  486  that is positioned in one application within the left femoral artery  26  when the cannula  484  is fully inserted so that blood drawn from the left femoral artery  26  is directed through the inflow port  486  into a first lumen  488  in the cannula  484 . The inflow port  486  can also be positioned in any other suitable location within the vasculature, described herein or apparent to one skilled in the art. This blood is then pumped through a second lumen  490  in the cannula  484  and out through an outflow port  492  at the distal end of the cannula  484 . The outflow port  492  may be situated within, for example, a mesenteric artery  494  such that blood flow results from the left femoral artery  26  to the mesenteric artery  494 . The blood could discharge, for example, directly into the descending aorta proximate an arterial branch, such as the renal arteries, the left subclavian artery, or directly into the peripheral mesenteric artery  494 , as illustrated in  FIG. 11 . Where there is a desire for the patient to be ambulatory, the multilumen cannula  484  preferably is made of material sufficiently flexible and resilient to permit the patient  12  to comfortably move about while the cannula  484  is indwelling in the patient&#39;s blood vessels without causing any vascular trauma. Further details of various embodiments of the multilumen cannula  460  are described below in connection with  FIGS. 17-26 .  
       FIG. 12  shows another heart assist system  510  that takes further advantage of the supplemental blood perfusion and heart load reduction benefits while remaining minimally invasive in application. The heart assist system  510  is an extracardiac pumping system that includes a pump  532 , an inflow. conduit  550  and an outflow conduit  552 . In the illustrated embodiment, the inflow conduit  550  comprises a vascular graft. The vascular graft conduit  550  and the outflow conduit  552  are fluidly coupled to pump  532 . The pump  532  is configured to pump blood through the patient at subcardiac volumetric rates, and has an average flow rate that, during normal operation thereof, is substantially below that of the patient&#39;s heart when healthy. In one variation, the pump  532  may be a rotary pump. Other pumps described herein, or any other suitable pump can also be used in the extracardiac pumping system  510 . In one application, the pump  532  is configured so as to be implantable.  
      The vascular graft  550  has a first end  554  and a second end  556 . The first end  554  is sized and configured to couple to a non-primary blood vessel  558  subcutaneously to permit application of the extracardiac pumping system  510  in a minimally-invasive procedure. In one application, the vascular graft conduit  550  is configured to couple to the blood vessel  558  via an anastomosis connection. The second end  556  of the vascular graft  550  is fluidly coupled to the pump  532  to conduct blood between the non-primary blood vessel  558  and the pump  532 . In the embodiment shown, the second end  556  is directly connected to the pump  532 , but, as discussed above in connection with other embodiments, intervening fluid conducting elements may be interposed between the second end  556  of the vascular graft  550  and the pump  532 . Examples of arrangements of vascular graft conduits may be found in U.S. application Ser. No. 09/780,083, filed Feb. 9, 2001, entitled EXTRA-CORPOREAL VASCULAR CONDUIT, which is hereby incorporated by reference in its entirety and made a part of this specification.  
       FIG. 12  illustrates that the present inventive embodiment further comprises means for coupling the outflow conduit  552  to the vascular graft  550 , which may comprise in one embodiment an insertion site  560 . In the illustrated embodiment, the insertion site  560  is located between the first end  554  and the second end  556  of the vascular graft  550 . The outflow conduit  552  preferably is coupled with a cannula  562 . The cannula  562  may take any suitable form, e.g., incorporating one or more of the features of the cannulae discussed below in connection with  FIGS. 17-26 .  
      The insertion site  560  is configured to receive the cannula  562  therethrough in a sealable manner in the illustrated embodiment. In another embodiment, the insertion site  560  is configured to receive the outflow conduit  552  directly. The cannula  562  includes a first end  564  sized and configured to be inserted through the insertion site  560 , through the cannula  550 , and through the non-primary blood vessel  558 . The conduit  552  has a second end  566  fluidly coupled to the pump  532  to conduct blood between the pump  532  and the blood vessel  558 .  
      The extracardiac pumping system  510  can be applied to a patient, as shown in  FIG. 12 , so that the outflow conduit  552  provides fluid communication between the pump  532  and a location upstream or downstream of the point where the cannula  562  enters the non-primary blood vessel  558 . In another application, the cannula  562  is directed through the blood vessel to a different blood vessel, upstream or downstream thereof. Although the vascular graft  550  is described above as an “inflow conduit” and the conduit  552  is described above as an “outflow conduit,” in another application of this embodiment, the blood flow through the pumping system  510  is reversed (i.e., the pump  532  pumps blood in the opposite direction), whereby the vascular graft  550  is an outflow conduit and the conduit  552  is an inflow conduit.  
       FIG. 13  shows a variation of the extracardiac pumping system shown in  FIG. 12 . In particular, a heart assist system  570  includes an inflow conduit  572  that comprises a first end  574 , a second end  576 , and means for connecting the outflow conduit  552  to the inflow conduit  572 . In one embodiment, the inflow conduit  572  comprises a vascular graft. The extracardiac pumping system  570  is otherwise similar to the extracardiac pumping system  510 . The means for connecting the conduit  552  to the inflow conduit  572  may comprise a branched portion  578 . In one embodiment, the branched portion  578  is located between the first end  574  and the second end  576 . The branched portion  578  is configured to sealably receive the distal end  564  of the outflow conduit  552 . Where, as shown, the first end  564  of the outflow conduit  552  comprises the cannula  562 , the branched portion  578  is configured to receive the cannula  562 . The inflow conduit  572  of this arrangement comprises in part a multilumen cannula, where the internal lumen extends into the blood vessel  558 . Other multilumen catheter arrangements are shown in U.S. application Ser. No. 10/078,283, incorporated by reference herein above.  
      2. Single-Site Application of Intravascular Pumping Systems  
       FIGS. 14-16  illustrate extracardiac heart assist systems that employ intravascular pumping systems. Such systems take further advantage of the supplemental blood perfusion and heart load reduction benefits discussed above while remaining minimally invasive in application. Specifically, it is contemplated to provide an extracardiac pumping system that comprises a pump that is sized and configured to be at least partially implanted intravascularly in any location desirable to achieve those benefits, while being insertable through a non-primary vessel.  
       FIG. 14  shows a heart assist system  612  that includes a pumping means  614  comprising preferably one or more rotatable impeller blades  616 , although other types of pumping means  614  are contemplated, such as an archimedes screw, a worm pump, or other means by which blood may be directed axially along the pumping means from a point upstream of an inlet to the pumping means to a point downstream of an outlet from the pumping means. Where one or more impeller blades  616  are used, such as in a rotary pump, such impeller blades  616  may be supported helically or otherwise on a shaft  618  within a housing  620 . The housing  620  may be open, as shown, in which the walls of the housing  620  are open to blood flow therethrough. The housing  620  may be entirely closed, if desired, except for an inlet and outlet (not shown) to permit blood flow therethrough in a more channel fashion. For example, the housing  620  could be coupled with or replaced by a cannula with a downstream blood flow enhancing portion, such as those illustrated in  FIGS. 17-26 . The heart assist system  612  serves to supplement the kinetic energy of the blood flow through the blood vessel in which the pump is positioned, e.g., the aorta  16 .  
      The impeller blade(s)  616  of the pumping means  614  of this embodiment may be driven in one or a number of ways known to persons of ordinary skill in the art. In the embodiment shown in  FIG. 14 , the impeller blade(s)  616  are driven mechanically via a rotatable cable or drive wire  622  by driving means  624 , the latter of which may be positioned corporeally (intra- or extra-vascularly) or extracorporeally. As shown, the driving means  624  may comprise a motor  626  to which energy is supplied directly via an associated battery or an external power source, in a manner described in more detail herein. It is also contemplated that the impeller blade(s)  616  be driven electromagnetically through an internal or external electromagnetic drive. Preferably, a controller (not shown) is provided in association with this embodiment so that the pumping means  614  may be controlled to operate in a continuous and/or pulsatile fashion, as described herein.  
      Variations of the intravascular embodiment of  FIG. 14  are shown in  FIGS. 15 and 16 . In the embodiment of  FIG. 15 , an intrasvascular extracardiac system  642  comprising a pumping means  644 , which may be one of several means described herein. The pumping means  644  may be driven in any suitable manner, including means sized and configured to be implantable and, if desired, implantable intravascularly, e.g., as discussed above. For a blood vessel (e.g., descending aorta) having a diameter “A”, the pumping means  644  preferably has a meaningfully smaller diameter “B”. The pumping means  644  may comprise a pump  646  having an inlet  648  and an outlet  650 . The pumping means  644  also comprises a pump driven mechanically by a suitable drive arrangement in one embodiment. Although the vertical arrows in  FIG. 15  illustrate that the pumping means  644  pumps blood in the same direction as the flow of blood in the vessel, the pumping means  644  could be reversed to pump blood in a direction generally opposite of the flow in the vessel.  
      In one embodiment, the pumping means  644  also includes a conduit  652  in which the pump  646  is housed. The conduit  652  may be relatively short, as shown, or may extend well within the designated blood vessel or even into an adjoining or remote blood vessel at either the inlet end, the outlet end, or both. The intravascular extracardiac system  642  may further comprise an additional parallel-flow conduit, as discussed below in connection with the system of  FIG. 16 .  
      The intrasvascular extracardiac system  642  may further comprise inflow and/or outflow conduits or cannulae (not shown) fluidly connected to the pumping means  644 , e.g., to the inlet and outlet of pump  646 . Any suitable conduit or cannula can be employed. For example, a cannula having a downstream blood flow enhancing portion, such as the any of the cannulae of  FIGS. 17-26 , could be coupled with an intrasvascular extracardiac system.  
      In another embodiment, an intrasvascular pumping means  644  may be positioned within one lumen of a multilumen catheter so that, for example, where the catheter is applied at the left femoral artery, a first lumen may extend into the aorta proximate the left subclavian and the pumping means may reside at any point within the first lumen, and the second lumen may extend much shorter just into the left femoral or left iliac. Such a system is described in greater detail in U.S. application Ser. No. 10/078,283, incorporated by reference herein above.  
       FIG. 16  shows a variation of the heart assist system of  FIG. 15 . In particular the intravascular system may further comprise an additional conduit  660  positioned preferably proximate the pumping means  644  to provide a defined flow path for blood flow axially parallel to the blood flowing through the pumping means  644 . In the case of the pumping means  644  of  FIG. 16 , the means comprises a rotatable cable  662  having blood directing means  664  supported therein for directing blood axially along the cable. Other types of pumping means are also contemplated, if desired, for use with the additional conduit  660 .  
      The intravascular extracardiac system described herein may be inserted into a patient&#39;s vasculature in any means known by one of ordinary skill or obvious variant thereof. In one method of use, such a system is temporarily housed within a catheter that is inserted percutaneously, or by surgical cutdown, into a non-primary blood vessel and advanced through to a desired location. The catheter preferably is then withdrawn away from the system so as not to interfere with operation of the system, but still permit the withdrawal of the system from the patient when desired. Further details of intravascular pumping systems may be found in U.S. patent application Ser. No. 10/686,040, filed Oct. 15, 2003, which is hereby incorporated by reference herein in its entirety.  
      C. Potential Enhancement of Systemic Arterial Blood Mixing  
      One of the advantages of the present invention is its potential to enhance mixing of systemic arterial blood, particularly in the aorta. Such enhanced mixing ensures the delivery of blood with higher oxygen-carrying capacity to organs supplied by arterial side branches off of the aorta. A method of enhancing mixing utilizing the present invention preferably includes taking steps to assess certain parameters of the patient and then to determine the minimum output of the pump that, when combined with the heart output, ensures turbulent flow in the aorta, thereby enhancing blood mixing.  
      Blood flow in the aortic arch during normal cardiac output may be characterized as turbulent in the end systolic phase. It is known that turbulence in a flow of fluid through pipes and vessels enhances the uniform distribution of particles within the fluid. It is believed that turbulence in the descending aorta enhances the homogeneity of blood cell distribution in the aorta. It is also known that laminar flow of viscous fluids leads to a higher concentration of particulate in the central portion of pipes and vessels through which the fluid flows. It is believed that, in low flow states such as that experienced during heart failure, there is reduced or inadequate mixing of blood cells leading to a lower concentration of nutrients at the branches of the aorta to peripheral organs and tissues. As a result, the blood flowing into branch arteries off of the aorta will likely have a lower hematocrit, especially that flowing into the renal arteries, the celiac trunk, the spinal arteries, and the superior and inferior mesenteric arteries. That is because these branches draw from the periphery of the aorta The net effect of this phenomenon is that the blood flowing into these branch arteries has a lower oxygen-carrying capacity, because oxygen-carrying capacity is directly proportional to both hematocrit and the fractional O 2  saturation of hemoglobin. Under those circumstances, it is very possible that these organs will experience ischemia-related pathology.  
      The phenomenon of blood streaming in the aorta, and the resultant inadequate mixing of blood resulting in central lumenal concentration of blood cells, is believed to occur when the Reynolds number (N R ) for the blood flow in the aorta is below 2300. To help ensure that adequate mixing of blood will occur in the aorta to prevent blood cells from concentrating in the center of the lumen, a method of applying the present invention to a patient may also include steps to adjust the output of the pump to attain turbulent flow within the descending aorta upstream of the organ branches; i.e., flow exhibiting a peak Reynolds number of at least 2300 within a complete cycle of systole and diastole. Because flow through a patient is pulsatile in nature, and not continuous, consideration must be given to how frequently the blood flow through the aorta has reached a certain desired velocity and, thus, a desired Reynolds number. The method contemplated herein, therefore, should also include the step of calculating the average Womersley number (N W ), which is a function of the frequency of the patient&#39;s heart beat. It is desired that a peak Reynolds number of at least 2300 is attained when the corresponding Womersley number for the same blood flow is approximately 6 or above.  
      More specifically, the method may comprise calculating the Reynolds number for the blood flow in the descending aorta by determining the blood vessel diameter and both the velocity and viscosity of the fluid flowing through the aorta. The Reynolds number may be calculated pursuant to the following equation:  
         N   R     =       V   ·   d     ν         
 
      where: V=the velocity of the fluid; d=the diameter of the vessel; and υ=the viscosity of the fluid. The velocity of the blood flowing through the aorta is a function of the cross-sectional area of the aorta and the volume of flow therethrough, the latter of which is contributed both by the patient&#39;s own cardiac output and by the output of the pump of the present invention. Velocity may be calculated by the following equation:  
       V   =     Q     π   ⁢           ⁢     r   2             
 
      where Q=the volume of blood flowing through the blood vessel per unit time, e. g., the aorta, and r=radius of the aorta. If the relationship between the pump output and the velocity is already known or independently determinable, the volume of blood flow Q may consist only of the patient&#39;s cardiac output, with the knowledge that that output will be supplemented by the subcardiac pump that is part of the present invention. If desired, however, the present system can be implemented and applied to the patient first, before calculating Q, which would consist of the combination of cardiac output and the pump output.  
      The Womersley number may be calculated as follows: 
 
 N   W   =r{square root}{square root over (2πω/)}   υ 
 
      where r is the radius of the vessel being assessed, ω is the frequency of the patient&#39;s heartbeat, and υ=the viscosity of the fluid. For a peak Reynolds number of at least 2300, a Womersley number of at least 6 is preferred, although a value as low as 5 would be acceptable.  
      By determining (i) the viscosity of the patient&#39;s blood, which is normally about 3.0 mm 2 /sec sec (kinematic viscosity), (ii) the cardiac output of the patient, which of course varies depending upon the level of CHF and activity, and (iii) the diameter of the patient&#39;s descending aorta, which varies from patient to patient but is about 21 mm for an average adult, one can determine the flow rate Q that would result in a velocity through the aorta necessary to attain a Reynolds number of at least 2300 at its peak during the patient&#39;s heart cycle. Based upon that determination of Q, one may adjust the output of the pump of the present invention to attain the desired turbulent flow characteristic through the aorta, enhancing mixing of the blood therethrough.  
      One may use ultrasound (e.g., echocardiography or abdominal ultrasound) to measure the diameter of the aorta, which is relatively uniform in diameter from its root to the abdominal portion of the descending aorta. Furthermore, one may measure cardiac output using a thermodilution catheter or other techniques known to those of skill in the art. Finally, one may measure viscosity of the patient&#39;s blood by using known methods; for example, using a capillary viscosimeter. It is expected that in many cases, the application of this embodiment of the present method will provide a basis to more finely tune the system to more optimally operate the system to the patient&#39;s benefit. Other methods contemplated by the present invention may include steps to assess other patient parameters that enable a person of ordinary skill in the art to optimize the present system to ensure adequate mixing within the vascular system of the patient.  
      Alternative inventive methods that provide the benefits discussed herein include the steps of, prior to applying a shape change therapy, applying a blood supplementation system (such as one of the many examples described herein) to a patient, whereby the methods are designed to improve the ability to reduce the size and/or wall stress of the left ventricle, or both ventricles, thus reducing ventricular loading. Specifically, one example of such a method comprises the steps of providing a pump configured to pump blood at subcardiac rates, providing inflow and outflow conduits configured to fluidly communicate with-non-primary blood vessels, fluidly coupling the inflow conduit to a non-primary blood vessel, fluidly coupling the outflow conduit to the same or different (primary or non-primary) blood vessel and operating the subcardiac pump in a manner, as described herein, to reduce the load on the heart, wherein the fluidly coupling steps may comprise anastomosis, percutaneous cannulazation, positioning the distal end of one or both conduits within the desired terminal blood vessel or any combination thereof. The method further comprises, after sufficient reduction in ventricular loading, applying a shape change therapy in the form of, for example, a cardiac reshaping device, such as those referred to herein, or others serving the same or similar function, for the purpose of further reducing the size of and/or wall stress on one or more ventricles and, thus, the heart, and/or for the purpose of maintaining the patient&#39;s heart at a size sufficient to enhance recovery of the patient&#39;s heart.  
     II. Cannulae and Cannula System for Use in Heart Assit Systems  
      With reference to  FIGS. 17-26 , various embodiments of perfusion cannula systems comprise a cannula body and a means for enhancing blood flow past the cannula body when the cannula body resides within the patient. The enhancing means preferably is capable of selectively enhancing blood flow around the cannula body within the vasculature of the patient. For example, as shown in  FIGS. 17 and 18 , and discussed further below, in some embodiments, the enhancing means comprises at least one balloon. In other embodiments, as shown in  FIG. 19 , and discussed further below, the enhancing means comprises at least one aperture that can be selectively covered and uncovered by a sleeve.  
      With reference to  FIG. 17 , one embodiment of a perfusion cannula system includes a cannula  700  that is configured to direct blood through the vasculature of a patient. The cannula system also includes a balloon  704  that is coupled with the cannula  700 . The balloon  704  preferably is located on the exterior of the cannula  700 . In one embodiment, the cannula  700  and the balloon  704  are physically distinct, i.e., formed in separate processes and later coupled, and together form a catheter system. In other embodiments, the cannula  700  and the balloon  704  are formed together and the balloon  704  is considered to be a part of the cannula  700 . As discussed in greater detail below, the balloon  704  may be deployed to provide space between a vessel wall and the cannula  700  when the cannula  700  resides within the patient. The balloon  704  may thereby enable or enhance passive perfusion of blood past the cannula  700 . The term “passive perfusion” is used in its ordinary sense and is a broad term that includes providing a path for blood flow under prevailing blood pressure within the vessel and that is not otherwise externally assisted.  
      The cannula  700  comprises a proximal end  708 , a distal end  712 , and at least one lumen that extends therebetween. With reference to  FIG. 17 , the cannula  700  defines a first lumen  716  that extends between the proximal end  708  and the distal end  712  and also defines a second lumen  720  that extends between the proximal end  708  and a distal end  724 . The lumens  716 ,  720  may provide for inflow and outflow of blood in connection with a heart assist system, such as those discussed above in connection with  FIGS. 10-16 . Although shown as a multilumen cannula, the cannula  700  could also be configured as a single lumen cannula, which could be employed in multi-site applications, such as those shown in  FIGS. 1-9 .  
      One or more apertures  726  may be formed in the cannula  700  proximate the distal end  712 , although such apertures may also be formed proximate the distal end  724 . The apertures  726  may be positioned close together or spaced circumferentially around the portion of the cannula  700  defining the lumen  716 . The apertures  726  decrease the pressure drop across the distal end  712 , thereby minimizing damage to vessel walls from jetting effects. Where one ore more apertures are formed proximate the distal end  724 , the apertures decrease the pressure differential across the distal end  724 , thereby minimizing the tendency of the vessel wall to be sucked into the distal end  724 . Further tip arrangements that may be advantageously employed that provide desired outflow characteristics are described in more detail in U.S. patent application Ser. No. 10/706,346, filed Nov. 12, 2003, which is hereby expressly incorporated by reference herein in its entirety.  
      The lumens  716 ,  720  of the cannula  700  may be arranged in any of a number of different ways. For example, the two lumens may be joined in a side-by-side manner, forming a “figure-8” when viewed from the proximal end  708 . In another embodiment, the cannula  700  may contain within it two or more side-by-side lumens. A cylindrical cannula body could be formed with a wall extending across the cylinder at a diameter to form two lumens. A cylindrical cannula body with concentrically positioned lumens is also contemplated.  
      The cannula system also includes an auxiliary lumen  728  that is in fluid communication with the balloon  704 . The auxiliary lumen  728  may be defined in the body of the cannula  700 . The lumen  728  preferably extends from the proximal end  708  of the cannula  700  to the balloon  704 . The lumen  728  is referred to herein as an “auxiliary lumen” because it is generally substantially smaller than the lumens  716 ,  720  and because it enables a function that is not primary to the operation of the cannula  700 . The lumen  728  is one means for deploying the balloon  704  within the vasculature and in one embodiment is an inflation lumen for the balloon  704 . Preferably, the lumen  728  may be selectively fluidly coupled with a source of any suitable inflation media. The inflation media may be another means for deploying the balloon  704 . The inflation media may include a suitable gas or liquid, such as saline. The inflation media may be delivered by way of a syringe (not shown), which is another means for deploying the balloon  704 .  
      The balloon  704  is formed of an inflatable material that can be actuated from a deflated state to an inflated state. When in the deflated state, the balloon  704  preferably substantially conforms to at least a portion of the outside surface of the cannula  700 . The balloon  704  is also one form of a collapsible element that can be selectively collapsed to ease insertion of the cannula system  700  into the vasculature. After being inserted into the patient, as described in more detail below, the balloon  704  may be inflated to the inflated state shown in  FIG. 17 . Thus, the balloon  704  is one form of an expandable element, e.g., one that may be selectively expanded to provide the function of passive perfusion, as discussed herein. Other forms of collapsible and expandable elements are also possible, such as those that employ a mechanically actuatable element and those that automatically collapse or expand, such as self-expanding elements.  
      In one embodiment, the balloon  704  has a tubular configuration when in the inflated state. The tubular configuration of the balloon  704  provides an inside surface that defines a perfusion lumen  732 . The perfusion lumen  732  is a generally longitudinally extending lumen, e.g., one that is generally parallel to the lumens  716 ,  720 . As shown in  FIG. 22  and discussed in more detail below, the perfusion lumen  732  has a generally circular cross-section in one embodiment and is large enough to permit a substantial amount of blood to flow therethrough. The flow through the perfusion lumen  732  is directed beyond a proximal end  734  of the balloon  704  and beyond the insertion site of the cannula  700  into the vasculature downstream to tissue that might otherwise be deprived of oxygenated blood.  
      Additional features that may be incorporated into the cannula  700  include a tapered tip  736  at the first distal end  712  and/or a tapered tip  740  at the second distal end  724 . The tapered tips  736 ,  740  may facilitate insertion and threading of the cannula  700  into the patient. The cannula  700  may also be provided with a radiopaque marker  744 , which may be positioned proximate the distal end  712 . The cannula  700  could further comprise markings  748  near the proximal end  708  and a known distance from one or more of the distal ends  712 ,  724 . The markings  748 , as well as the radiopaque marker  744 , can be used to accurately position the cannula  700  when inserted within the patient.  
      With reference to  FIG. 18 , in another embodiment a cannula  800  comprises one or more inflatable members or balloons  804  extending between a proximal end  808  and a distal end  812 . In the embodiment illustrated in  FIG. 18 , a plurality of balloons  804  are provided. The balloons  804  are positioned and sized such that when the cannula  800  resides in the patient (described below), the balloons  804  reside entirely within the patient&#39;s body. The balloons  804  are spaced radially about the cannula  800 , e.g., equally spaced around the cannula  800 . As described above, the balloons  804  may be connected to the cannula  800  in a variety of ways. The balloons  804  can be formed integrally with the cannula  800 . The balloons  804  can also be formed separately and coupled to the cannula  800  in any suitable manner. One purpose of the balloons  804  is to provide passive perfusion, e.g., to selectively permit the passive flow of blood downstream to the cannula to enhance perfusion. The balloons  804  therefore comprise a means for creating space around the cannula  800  within the vasculature to permit blood flow past the cannula  800 .  
      The balloons  804  are one form of an expandable element, e.g., one that may be selectively expanded to provide the function of passive perfusion, as discussed above. The balloon  804  is also one form of a collapsible element that is selectively collapsible to ease insertion of a cannula system into the vasculature. Other forms of collapsible and expandable elements are also possible, such as those that employ one or more mechanically actuatable elements and those that employ one or more elements that automatically collapse or expand, such as self-expanding elements.  
      The balloons  804  may be made of inflatable material, e.g., one capable of taking on an inflated and deflated state. In the deflated state, the balloons  804  would conform to at least a portion of the outside surface of the cannula  800 . Once inserted within the patient, as described in more detail below, the balloons  804  would be inflated to the inflated state shown in  FIG. 18 . The inflatable balloons  804  can have any suitable configuration. Preferably, when the balloons  804  are deployed within a patient&#39;s body they contact the surface of the vessel wall. Here, the balloons  804  are used primarily to create a space between the cannula  800  and the vessel wall to permit the passive flow of blood downstream of the cannula site to enhance perfusion, e.g., to provide passive perfusion. Blood preferably flows through spaces formed alongside the inflated balloons  804  between the cannula  800  and a vessel wall. As described previously, the balloons  804  can be inflated by filling the balloons  804  with gas or liquid through auxiliary lumens  828  defined in the body of the cannula  800 , or in any other suitable manner.  
      With reference to  FIG. 19 , in another embodiment, a cannula system  900  comprises a cannula  902  having an aperture  968  formed in the body thereof and a sleeve  972 . In some embodiments a plurality of apertures  968  may be provided. The apertures  968  can be positioned on the cannula system  900  near the proximal end  912 . The apertures  968  preferably are formed on the body of the cannula  902  and provide fluid communication between one of the lumens  916 ,  920  and the blood vessel in which the cannula  902  resides.  
      In one embodiment the sleeve  972  is carried by the cannula  902  and is configured to be moveable relative to the apertures  968  to selectively cover and uncover the apertures  968  as desired. The sleeve  972  can be carried on either the outside or the inside of the cannula  902 . For example, when the apertures  968  are formed on the body of the cannula  902  to provide fluid communication between the lumen  916  and the blood vessel, the sleeve  972  could be carried within the lumen  916 . The sleeve  972  could be carried within the lumen  920  in a similar fashion to selectively cover and uncover apertures formed in the body of the cannula  902  to provide fluid communication between the lumen  920  and the blood vessel. In the illustrated embodiment, the sleeve  972  is on the outside of the body of the cannula  902 . The sleeve  972  can be configured to move radially with respect to the cannula  902 . The sleeve  972  can also be configured to move longitudinally, e.g., distally or proximally, with respect to the cannula  902 .  
      The apertures  968  can be selectively uncovered while the cannula system  900  resides within a patient&#39;s body. Here, the sleeve  972  and apertures  968  are used primarily to selectively provide active perfusion of blood downstream of the location of the cannula  902  within the blood vessel. As used herein “active perfusion” is used in its ordinary sense and is a broad term that includes providing additional flow of blood under external blood pressure, e.g., the blood pressure generated by a pump forcing blood into the lumen  916 , into the vessel to increase downstream flow of blood.  
      Any of the cannulae described herein may be made from various materials to improve their viability in long-term treatment applications. For example, it is preferred that the biocompatibility of the cannula be improved compared to uncoated cannulae to prevent adverse reactions such as compliment activation and the like. To prevent such side effects, the interior lumens of the cannulae can be coated with biocompatible materials. Also known in the art are anti-bacterial coatings. Such coatings may be very useful on the outer surface of the cannula. This is especially true at or about where the cannula enters the patient&#39;s skin. At such a location, the patient is vulnerable to introduction of bacteria into the body cavity. Anti-bacterial coatings can reduce the likelihood of infection and thus improve the viability of long-term treatments.  
      In one application, a cannula may be integrated into a heart assist system. The heart assist system may be configured in any number of ways. Various heart assist systems have been described above. In addition, as shown in to  FIG. 20 , in one embodiment such a system comprises the cannula  700 , an inflow conduit  776 , an outflow conduit  780  and a pump  784 . One end of the outflow conduit  780  may be connected to the proximal end of the first lumen  716 , while the other end is connected to the inlet of the pump  784 . One end of the inflow conduit  776  may be connected to the proximal end of the second lumen  720 , while the other end is connected to the outlet of the pump  784 . This results in a flow from the first distal end  712  to the second distal end  724 . Of course, the flow direction may be reversed using the same cannula, resulting in a flow from the second distal end  724  to the first distal end  712 . In that case, the outflow conduit  780  is connected to the proximal end of the second lumen  720  and the inflow conduit  776  is connected to the proximal end of the first lumen  716 .  
      Referring to  FIG. 20 , the cannula  700  may be applied to a patient in an arterial-arterial fashion, e.g., with the cannula  700  inserted into the femoral artery  788  of the patient  792 . Where provided, the radiopaque marker  744  is used to track the insertion of the cannula  700  so that the cannula may be positioned at a desired site within the patient&#39;s vascular system. As mentioned above, markings  748  near the proximal end  708  could also be used to locate the distal end or ends of the cannula  700 . In one application, the first distal end  712  may advance up to the thoracic aorta or even further.  
      In operation, the pump draws blood from the patient&#39;s vascular system in the area near the distal end  724  and into the second lumen  720 . The blood is further drawn into the lumen of the inflow conduit  780  and into the pump  784 . The pump  784  then expels the blood into the lumen of the outflow conduit  776 . The lumen of the outflow conduit  776  carries the blood into the second lumen  716  of the cannula  700  and back into the patient&#39;s vascular system in the area near the distal end  712 .  
      According to one method of treating a patient using an extracardiac heart assist system, the cannula system is inserted into the vasculature of a patient and selectively actuated to enhance blood flow past the cannula. As described in greater detail below, with reference to embodiments illustrated in  FIGS. 21-26 , the additional lumen, the inflatable members, and/or the sleeve and apertures selectively provide blood flow to the patient&#39;s vasculature downstream of where the cannulae reside in the vasculature to maintain or enhance perfusion of blood, e.g., by active or by passive perfusion.  
      Referring to  FIGS. 21 and 22 , the perfusion lumen  732  of the embodiment shown in  FIG. 17  is located entirely within the vessel  788  when the cannula  700  is inserted into the patient. In one embodiment, the lumen  732  can be selectively actuated by inflating the balloon  704  with the use of a syringe or other inflation means, such as, for example, those used for angioplasty balloons. The lumen  732  provides a pathway for blood flow to tissue downstream of the cannula so that the cannula  700  may maintain or increase the flow of blood to downstream tissue. In one embodiment, the lumen  732  is advantageously configured to extend the entire length of the potentially occluded portion of the vessel. For example, as shown in  FIG. 21 , the perfusion lumen  732  extends from a location distal of the distal end  724  at least to the vascular insertion site. This enables blood to enter the lumen  732  upstream of the distal end  724  and to be conveyed past the occluded region of the vessel to a location where the blood exiting the lumen  732  can flow substantially uninhibited beyond the insertion site. The lumen  732 , thus, provides passive perfusion. If desired, apertures may be included in one of the other two lumens  716 ,  720  to supplement passive perfusion with active perfusion.  
      Referring to  FIGS. 23 and 24 , the inflatable members or balloons  804  of the embodiment shown in  FIG. 18  are located entirely within the vessel  888  when the cannula  800  is inserted into the patient. In one embodiment, the balloons  804  can be selectively actuated by inflating the balloons  804  with the use of a syringe or other inflation means, as described above. Spaces  866  created alongside the balloons  804  provide pathways for blood to flow to tissue downstream of the cannula  800  providing passive perfusion. If desired, apertures may be included in one of the other two lumens  816 ,  820  to supplement passive perfusion with active perfusion.  
      Referring to  FIGS. 25 and 26 , the cannula system  900 , as described with reference to  FIG. 19 , comprises features that will maintain or increase the blood flow to downstream tissue when the cannula is inserted into the patient. The perfusion cannula system  900  can be selectively actuated by moving the sleeve  972  relative the apertures  968  to uncover the apertures  968 . In one embodiment, selectively actuating the cannula system  900  comprises twisting the cannula system within the vasculature to expose the apertures  968 . The apertures  968  provide for fluid communication between at least one lumen  916  or  920  and the patient&#39;s blood vessel  988 . The apertures  968  thus provide active perfusion of the downstream tissues.  
      Although the foregoing invention has been described in terms of certain preferred embodiments, other embodiments will be apparent to those of ordinary skill in the art. Additionally, other combinations, omissions, substitutions and modification will be apparent to the skilled artisan, in view of the disclosure herein. Accordingly, the present invention is not intended to be limited by the recitation of the preferred embodiments, but is instead to be defined by reference to the appended claims.