Patent Abstract:
A system for delivering blood, cardioplegia solution, and other medications or fluids in a pulsatile flow pattern to a patient during cardiopulmonary bypass is disclosed. In a preferred embodiment, a pumping apparatus having at least one chamber is utilized in which a pumping action is achieved by compressing one of the chambers with a piston mechanism, while allowing the other chamber to fill with fluid via retracting its respective piston. The instantaneous flow rate of either of the chambers is determined by the speed of the piston. In a preferred embodiment, a pulsatile flow of fluid is achieved by cyclically alternating the velocity of the piston between two different speeds. A desired average flow rate and/or delivery pressure and/or constant pulse pressure is maintained by adjusting the alternating velocities at the desired frequency and duty cycle. The calculations necessary to obtain a desired average flow rate are performed by a microprocessor, which also controls the movement of the pistons.

Full Description:
CROSS-REFERENCE TO RELATED PATENTS 
     The present application is related to the following commonly-assigned, issued U.S. patents, which are incorporated herein by reference in their entirety: U.S. Pat. No. RE36,386 (ABBOTT et al.) Nov. 9, 1999, U.S. Pat. No. 5,573,502 (LECOCQ et al.) Nov. 12, 1996, U.S. Pat. No. 5,638,737 (MATTSON et al.) Jun. 17, 1997, and U.S. Pat. No. 5,645,531 (THOMPSON et al.) Jul. 8, 1997. 
     BACKGROUND OF THE INVENTION 
     1. Technical Field 
     The present invention relates generally to equipment used to deliver fluids to a patient during surgery. Specifically, the present invention is directed to a device for delivering cardioplegia solution during open-heart surgery and other surgical procedures requiring myocardial protection. 
     2. Background Art 
     Heart surgery is among the most complex of surgical fields. Because under normal conditions, the heart muscle is in a constant state of motion, special techniques must be used to make the heart sufficiently stationary to allow a surgeon to operate on it. Although some surgical procedures may be performed on a beating heart, the majority of open-heart and closed-heart procedures, including coronary artery bypass surgery, require that the heart be slowed or stopped and the aorta clamped before the cardiac portion of the surgery may begin. In such procedures, external equipment is used to form an extracorporeal circuit in the patient&#39;s circulatory system. Electric/mechanical pumps are used to pump the blood to an artificial oxygenator, then back into the patient, so as to temporarily replace the patient&#39;s heart and lungs during the procedure. This technique is known as a “cardiopulmonary bypass,” and it allows the surgical team to stop the heart, while still keeping the patient alive. 
     The heart muscle (myocardium), no less than any other organ of the body, must also be kept alive during the procedure. Indeed, the myocardium has a very low tolerance for ischemia (reduction in blood supply), due to its high oxygen requirements. Thus, special techniques are employed to protect the myocardium during a cardiopulmonary bypass. 
     Modern surgical teams often use induced cardioplegia to both stop the heart and protect it from the effects of ischemia. A potassium-based cardioplegic solution is infused into the coronary arteries, usually at a low temperature. The potassium infusion causes an immediate cardiac arrest, while the typically low temperature of the solution reduces the heart&#39;s rate of oxygen consumption. There are two commonly-employed cardioplegic methods, blood cardioplegia and crystalloid cardioplegia. Blood cardioplegia is a solution that is mixed with oxygenated blood from the extracorporeal circuit. Crystalloid cardioplegic solution is a non-cellular solution with a saline or balanced electrolyte base such as Ringer&#39;s solution. Nowadays, cardioplegia may bedelivered through antegrade (that is, directly through the coronary arteries) or retrograde (through the coronary sinus vein) routes. 
     During cardiopulmonary bypass, both blood and cardioplegia solution must be circulated through the patient&#39;s body. Since the heart is no longer available to maintain the patient&#39;s circulation, artificial pump means must be employed. The most commonly employed pump is the DeBakey roller pump, which is described in U.S. Pat. No. 2,018,998 (DEBAKEY et al.) Oct. 29, 1935. The DeBakey pump uses a pair of rollers to create a peristaltic action against a flexible tube. Centrifugal pumps are also employed. Both of these types of pumps produce a relatively constant rate of flow. 
     Recent research, however, suggests that better cardiac perfusion is obtained with a pulsatile flow than with a constant-rate flow. The heart, after all, is a reciprocating pump and delivers a pulsatile flow. A number of designs have been developed to introduce a pulsatile component to extracorporeal circulation. These designs generally fall into two categories. A first category consists of those devices that combine a roller or centrifugal pump with an additional device that periodically compresses the tube through which the blood or cardioplegia flows. Examples of these devices include U.S. Pat. No. 4,116,589 (RISHTON) Sep. 26, 1978, and U.S. Pat. No. 6,620,121 (MCCOTTER) Sep. 16, 2003. 
     A second category consists of devices in which the pump itself is used to produce a pulsatile flow. In one type of pump, such as that in U.S. Pat. No. 5,702,358, the number of revolutions per minute (RPM) of a centrifugal pump is varied in a periodic fashion to achieve a roughly pulsatile flow. In U.S. Pat. No. 5,300,015 (RUNGE) Apr. 5, 1994, a type of peristaltic pump is described, which achieves a pulsatile flow. Both of these types of designs, however, are limited in their ability to produce a pulsatile flow of desired characteristics while still maintaining a desired average flow rate. 
     What is needed, therefore, is an apparatus for extracorporeal circulation that produces a significantly pulsatile flow, while still-maintaining a user-specified average flow rate. The present invention provides a solution to this and other problems, and offers other advantages over previous solutions. 
     SUMMARY OF THE INVENTION 
     A preferred embodiment of the present invention provides a system for delivering blood, cardioplegia solution, and other medications or fluids in a pulsatile flow to a patient during cardiopulmonary bypass. In one embodiment, a dual chambered pumping apparatus is utilized in which a pumping action is achieved by compressing one of the chambers with a piston mechanism, while allowing the other chamber to fill with fluid by retracting its respective piston. The instantaneous flow rate of either of the chambers is determined by the speed of the piston. In another embodiment, a single chambered pumping apparatus is used. In this embodiment, the piston can be delivering fluid during a stroke while at the same time filling the chamber on the opposite side of the piston. In a preferred embodiment, a pulsatile flow of fluid is achieved by cyclically alternating the velocity of the piston between two different speeds. A desired average flow rate is maintained by adjusting the alternating velocities and a duty cycle for the flow rate alternation. The calculations necessary to obtain a desired average flow rate are performed by a microprocessor, which also controls the movement of the pistons. 
     The foregoing is a summary and thus contains, by necessity, simplifications, generalizations, and omissions of detail; consequently, those skilled in the art will appreciate that the summary is illustrative only and is not intended to be in any way limiting. Other aspects, inventive features, and advantages of the present invention, as defined solely by the claims, will become apparent in the non-limiting detailed description set forth below. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The present invention may be better understood, and its numerous objects, features, and advantages made apparent to those skilled in the art by referencing the accompanying drawings, wherein: 
         FIG. 1  is a schematic diagram of a cardioplegic delivery system embodying a preferred embodiment of the present invention; 
         FIG. 2  is a schematic illustration of the functioning of one embodiment of a pump mechanism for use in a preferred embodiment of the present invention; 
         FIG. 3  is a plan view of one embodiment of a disposable fluid cassette for the pump mechanism of  FIG. 2 ; 
         FIG. 4  is an exploded, perspective view of a piston assembly in accordance with a preferred embodiment of the present invention; 
         FIG. 5  is a plan view of the piston of the piston assembly of  FIG. 4 ; 
         FIG. 6  is a sectional view of the piston along line  6 - 6  of  FIG. 5 ; 
         FIG. 7  is a plan view of the base of the piston assembly of  FIG. 4 ; 
         FIG. 8  is a sectional view of the base along line  8 - 8  of  FIG. 7 ; 
         FIG. 9  is a view from beneath a pump mechanism which accommodates the disposable fluid cassette of  FIG. 3 ; 
         FIG. 10  is a perspective view of the piston assembly of  FIG. 4  in a fully retracted state; 
         FIG. 11  is a perspective view of the piston assembly of  FIG. 4  in a fully advanced state; 
         FIG. 12  is a timing diagram illustrating a cycle of the blood/crystalloid pump depicted in  FIGS. 1-11  when operated in a non-pulsatile flow mode; 
         FIG. 13  is a timing diagram illustrating a cycle of the blood/crystalloid pump depicted in  FIGS. 1-11  when operated in a pulsatile flow mode in accordance with a preferred embodiment of the present invention; and 
         FIG. 14  is a flowchart representation of a method of producing a pulsatile flow in accordance with a preferred embodiment of the present invention. 
     
    
    
     DETAILED DESCRIPTION 
     The following is intended to provide a detailed description of an example of the invention and should not be taken to be limiting of the invention itself. Rather, any number of variations may fall within the scope of the invention, which is defined in the claims following the description. 
     A preferred embodiment of the present invention is directed to a system for delivering a pulsatile flow of blood and crystalloid cardioplegia solution to a patient undergoing open-heart surgery. In particular, a preferred embodiment of the present invention allows a perfusionist or surgeon to select between two different delivery modes, one in which fluids are delivered to the patient in a pulsatile flow and another in which fluids are delivered to the patient in a nonpulsatile flow. The two different modes of operation are supported by software, which controls the mechanical operation of the pump. The electromechanical components utilized in both modes are the same, the only difference between the two modes being the software processes used to control the electromechanical components of the system. 
       FIGS. 1-11 , therefore, describe the electromechanical aspects of the invention, which are common to both modes.  FIG. 12 , on the other hand, describes the operation of the nonpulsatile flow mode.  FIGS. 13 and 14  describe the operation of the pulsatile flow mode. 
     Turning now to  FIG. 1 , a cardioplegia delivery system  110  is established to provide solution to the heart of a patient during open heart surgery. The principal component of the cardioplegic solution is blood delivered to the system through conduit  112 , which is connected to the output of oxygenator  114  of the heart/lung machine sustaining the patient&#39;s vascular system while the heart is isolated during surgery. Oxygenator  114  provides arterial blood in the main extracorporeal circuit through a return line  116  to the patient&#39;s aorta. A fraction of the heart/lung machine output is diverted into conduit  112  for processing by the cardioplegic circuit and forwarding to the patient&#39;s heart through cardioplegia delivery line  118 . The cardioplegic solution flowing through line  118  may be delivered through antegrade line  120  to the aortic root, or through retrograde line  122  to the coronary sinus. 
     A crystalloid solution is stored in container  124  for combination with blood flowing in line  112  in a disposable pumping cassette  130   a . The output of cassette  130   a  is supplied through line  128  to a heat exchanger  135 . Pump cassette  130   a  is controlled by an electromechanical pump mechanism  130  in which cassette  130   a  is mounted. A second pump  131  controls cassette  131   a  containing potassium solution supplies its output to line  128  downstream from the pump cassette  131   a . A third pump  132  controls cassette  132   a  containing any additional drug supplies its output to line  128  downstream from the pump cassette  132   a.    
     In heat exchanger  135 , the cardioplegic solution is juxtaposed with a circulating temperature controlled fluid to adjust the temperature of the solution prior to forwarding the solution to the heart through line  118 . Preferably pump  133  circulates temperature controlled fluid through heat exchanger  135  either by push or pull.  FIG. 1  depicts a push-through coolant system in which a pump  133  circulates the control fluid through heat exchanger  135  and then to a two-way valve  134 , which valve  134  may direct the circulating fluid either to an ice bath  136  for cooling or a heated water reservoir  138  for heating. The circulating fluid is then pumped back through heat exchanger  135 , where the cardioplegia solution receives heating or cooling without contamination across a sealed heat transfer material or membrane within heat exchanger  135 . 
     The system includes patient monitoring of myocardial temperature along the signal path  142  and heart pressure along signal path  144  communicating to a central microprocessor control section  146 . In addition, the pressure and temperature of the cardioplegic solution in delivery line  118  is sensed via sensors  160  and the data is forwarded along signal paths  148  and  150  to control microprocessor  146 . Data input to microprocessor  146  through control panel  152  may include an advantageous combination of the following parameters: desired overall volumetric flow rate, desired blood/crystalloid ratio to be forwarded, desired potassium concentration to be established by pump  131 , desired supplemental drug concentration to be established by pump  132 , desired temperature of solution in cardioplegia delivery line  118 , and safety parameters such as the pressure of the cardioplegia solution in the system or in the patient. 
     In response to the data input through the control panel  152  and the monitored conditions along signal paths  142 ,  144 ,  148  and  150 , microprocessor control section  146  controls the operation of pump mechanism  130 , via signal path  154 , and of potassium pump  131  by way of a signal along path  156 . In addition, microprocessor control section  146  controls the circulation of fluid in the heat exchanger circulation path along signal path  158  either for obtaining a desired patient temperature or a desired output solution temperature. Further, the safety parameters such as pressure limits for a particular procedure or a particular patient may be controlled based upon input settings or based upon preset standards, as for example, one range of acceptable pressure limits for antegrade and another range for retrograde cardioplegia. 
     In accordance with a preferred embodiment of the invention, microprocessor controller section  146  controls the pump mechanism  130  to combine crystalloid from container  124  and blood from line  112  in any selected ratio over a broad range of blood/crystalloid ratios. Controller  146  may command the pump mechanism  130  to deliver blood without crystalloid addition. The blood/crystalloid ratio can be adjusted from an all blood mixture to an all crystalloid mixture, with multiple ratios in between. The rate of flow produced by the pump mechanism  130  of the combined output from disposable pump cassette  126  is preferably variable from 0 to 999 milliliters per minute. Potassium pump  131  is automatically controlled to maintain a constant potassium solution concentration. In other words, if the blood pump flow rate is increased, the potassium pump flow rate is automatically increased. 
       FIG. 2  illustrates one embodiment of a pump mechanism  130  for incorporation into a fluid delivery system such as that described in  FIG. 1 . The pump mechanism  130  operates on a flexible, disposable fluid cassette  220  which maintains the sterility of the fluid as it passes through the mechanism. The pump mechanism  130 , as described herein, features two piston assemblies  210   a ,  210   b . The piston assembly  210  of the present invention enables the mixing of multiple fluids in consistent, accurate ratios, and the delivery of such mixture at a definable, consistent volumetric flow rate. A fluid delivery system incorporating the present invention may have multiple applications within the medical industry and, in particular, applications in at least the areas of intravenous fluid delivery, limb perfusion, organ perfusion and cardioplegia delivery. Notwithstanding the foregoing, the present invention is adaptable to be incorporated into any variety of fluid delivery systems, whether medical related or not, and scalable to provide a large range of volumetric flow rates. 
       FIG. 3  illustrates one embodiment of a disposable fluid cassette  220 . The cassette  220  may be formed from two thin, flexible sheets of material, such as polyvinylchloride. The sheets are bonded together along a selected bond area  221  to form particularized open flow paths and chambers. Any number of techniques (as an example, RF welding) may be employed for such bonding. The thickness of the material should be such that variations which occur during manufacture should not significantly affect the volumetric accuracy of the fluid output of pump mechanism  130 . 
     The cassette  220  includes a first fluid inlet  222  and a second fluid inlet  224 . In a preferred embodiment, the first fluid inlet  222  accommodates blood and the second fluid inlet accommodates a crystalloid fluid typically used during open heart surgery. Fluid entry paths  223 ,  225  run respectively from inlets  222 ,  224  to a common inlet path  226 , which bifurcates to form inlet flow paths  228   a  and  228   b . Inlet flow paths  228   a  and  228   b  respectively terminate in pump chambers  230   a ,  230   b.    
     Outlet paths  232   a ,  232   b , forming the respective output pathways from pump chambers  230   a ,  230   b , join at a common outlet path  235 . The outlet path  235  is the gateway for passage of the first and second fluid mixture to other portions of the fluid delivery system. 
       FIG. 4  illustrates the piston assembly  210  of  FIG. 2 . The piston assembly  210  has a piston  240  and a base  250 , such base  250  being dimensioned to operatively receiving the piston  240 . From  FIGS. 5 and 6 , piston  240  includes a central hub  242  with a plurality of splines  244  extending outwardly therefrom. The plurality of splines  244  are integrally formed with the hub  242  and extend radially outward. The piston  240  generally forms a convex supporting surface  247 , wherein each spline  244  progresses from a full height at the hub  242  to a substantially lesser height at the perimeter of the piston  240 . For the preferred embodiment, the angular displacement of the supporting surface  247  corresponds, although in a differing direction of displacement, to an angular displacement of a facial surface, or receiving surface  258 , of the base  250 . 
     As shown in  FIG. 5 , the hub  242  can include a passage  246  extending through the piston  240 , such passage  246  extending along an axial centerline of the piston  240 . In the preferred embodiment, the passage  246  receives and carries a contact pressure sensor  248  (see  FIGS. 10 and 11 ). The incorporation of a pressure sensor  248  in the piston  240  permits monitoring of a fluid pressure within a pumping chamber associated with piston  240 . Consequently, the intrachamber fluid pressure is useful in determining: (i) the volumetric content of pumping chamber  230 , (ii) the presence of non-occluding valves adjacent pump chamber  230  and (iii) the presence of excessive fluid delivery pressures as well as excessive back-pressures presented to pump mechanism  130 . 
     As shown in  FIGS. 7 and 8 , the base  250  includes a collar  252  and a plurality of ribs  254 . The plurality of ribs  254  are integrally formed with collar  252  and extend radially inward to define a central passageway  256 . The base  250  is constructed so as to (i) permit the hub  242  to be movably received by the central passageway  256  and (ii) allow the plurality of splines  244  to be movably interposed between the plurality of ribs  254  (see  FIGS. 10 and 11 ). As shown in  FIG. 8 , the ribs  254  generally form a concave receiving surface  258  which inversely complements the convex supporting surface  247  of the piston  240 . Accordingly, each rib  254  progresses from a full height at the collar  252  to a substantially lesser height at the perimeter of central passageway  256 . In the preferred embodiment, the angular displacement of the receiving surface  258  is substantially 45 degrees. Further, the angular displacement of the supporting surface  247  of the piston  240  is substantially equivalent. 
     In the preferred embodiment, each spline  244  has a thickness substantially equal to that of each rib  254 . Therefore, when the base  250  receives the piston  240  there exists limited and tightly controlled clearance between any rib-spline interface, thereby preventing the opportunity for the cassette material to become pinched or positioned between the elements during operation. The piston  240  may be manufactured from a lubricated material such as acetyl fluoropolymer (for example, Delrin AF from DuPont, Co., Wilmington, Del.), and the base  250  from a glass reinforced polycarbonate (for example, a 10% glass material Lexan 500 from GE Plastics, Pittsfield, Mass.), to permit largely unrestricted motion of the piston  240  relative to the base  250  despite the potential for repeated contact between two elements. The number of splines  244  and ribs  254  should be such that the space  245  between each spline  244  and the space  255  between each rib  254  (such being substantially equivalent if the thickness of each spline  244  is substantially equivalent to the thickness of each rib  254 ) is of such a distance to enable the adjacent splines (or ribs as the case may be) to support the cassette  220  across the spaces  245 ,  255 . 
     The complementary shaping of the piston  240  and the base  250  enables a resting cassette pumping chamber  230  to be supported by a constant surface area throughout an entire stroke of the piston  240 , thereby foreclosing the opportunity for the cassette material to be stretched, unsupported or pinched during movement of the piston  240 . Furthermore, the geometric relation between the elements permits a mathematical relation to be established. In the preferred embodiment, for example, the diameter of the piston  240  linearly decreases, relative to the interior of the pumping chamber  230 , with the retraction of piston  240 . A similar relation exists for the advancement of piston  240 . Thus, during retraction of the piston  240 , an enclosed volume is created which increases as a quadratic function of the piston&#39;s  240  movement. The relation can be used to maintain a constant fluid flow rate because the rate of piston movement can be controlled to achieve a predetermined flow rate. 
     Although the preferred embodiment defines a base  250  having a receiving surface  258  with a 45-degree angular displacement along the plurality of ribs  254 , the angular displacement may measure from 30 to 60 degrees. Notwithstanding, the preferred embodiment ensures (i) a relatively significant pumping chamber volume, (ii) full support of the cassette pumping chamber  230  through an entire pumping stroke, and (iii) avoidance of trapped air within the pumping chamber  230 . 
       FIG. 9  is a rear view of the elements of the pumping mechanism  130  which accommodates the cassette  220  of  FIG. 3  (an outline of the cassette  220  is provided). The pumping mechanism  130  incorporates a pair of stepper motors, or pumping motors  272   a ,  272   b . The pumping motors  272   a ,  272   b  rotationally engage, through attached lead screws  243   a ,  243   b , a threaded portion  241   a ,  241   b  of each piston  240   a ,  240   b  (see  FIG. 2 ). Two drive motors  280 ,  282  control the operation of the mechanism&#39;s valves. Drive motor  280  engages cam shaft  292  (such driving inlet valves  286   a  and  286   b ) through a timing belt  298 . Drive motor  280  also engages cam shaft  294  (such driving outlet valves  288   a  and  288   b ) through a timing belt  299  which rotationally couples cam shafts  292  and  294 . Drive motor  282  engages cam shaft  290  (which drives inlet valves  284   a  and  284   b ) through an independent timing belt  296 . 
     Referring to both  FIGS. 3 and 9 , the interrelation of the pumping mechanism  130  and the fluid mixing operation are better illustrated. In short, mixing of a first and a second fluid, for the purposes of the illustrated embodiment, is accomplished through the continuous introduction of a first and a second fluid into multiple pumping chambers in a predefined, systematic pattern. The pumping mechanism  130 , through the operation of a series of valves, controls the flow of fluid throughout the cassette  220 . Specifically, a valve, if actuated, presses the first and second sheets of the cassette  220  together at a cassette valve location to occlude the valve location&#39;s corresponding flow path. 
     For pumping mechanism  130 , inlet valves  284   a ,  284   b ,  286   a ,  286   b  control the introduction of fluid into the pumping chambers  230   a ,  230   b . The inlet valves  284   a ,  284   b ,  286   a ,  286   b  act on the cassette  220  at valve locations  234   a ,  234   b ,  236   a  and  236   b , respectively. Outlet valves  288   a ,  288   b  control the flow of fluid from the pumping chambers  230   a ,  230   b  by acting on cassette valve locations  238   a ,  238   b . As an example, in preparation of filling pumping chamber  230   b , valve  286   a  (valve location  236   a ) is actuated to close inlet flow path  228   a , while valve  288   b  (valve location  238   b ) also occludes outlet path  232   b  to permit the accumulation of fluid within the pumping chamber  230   b . During filling, valves  284   a ,  284   b  and  286   b  (valve locations  234   a ,  234   b  and  236   b , respectively) open and close in a predetermined synchronized pattern to permit a ratio of the first and second fluids to enter the pumping chamber  230   b . Upon completion of the fill, valves  286   b  and  288   a  respectively occlude flow paths  228   b  and  232   a , and valve  288   b  is de-actuated to permit fluid to flow from the pumping chamber  230   b . Fluid movement, whether filling or being expelled from the pumping chambers  230   a ,  230   b , is initiated through the movement of the mechanism&#39;s pump assemblies  210   a ,  210   b.    
     Referring to  FIG. 2  and the operation of the pump mechanism  130 , a fastened retaining door  274  tightly constrains the cassette  220  against the upper surface of the pump mechanism. The retaining door  274  possesses a number of cavities  276   a ,  276   b , such number corresponding to the number of pump assemblies included within the pump mechanism  130 . The cavities  276   a ,  276   b  are complementary of and can fully receive at least a portion of the pistons  240   a ,  240   b  when such are in a fully advanced position. Accordingly, the conformance of the cavities  276   a ,  276   b  to the shaping of the pistons  240   a ,  240   b  enables the expulsion of substantially all the fluid from the pump chambers  230   a ,  230   b  for a full piston stroke. Complete fluid displacement makes such pumping mechanism  130  and its methodology suitable for single pumping stroke applications. 
     When the cassette  220  is operatively positioned in the pump mechanism  130 , the cassette pumping chambers  230   a ,  230   b  align with and rest upon the pump assemblies  210   a ,  210   b . The retaining door  274  effectively constrains the cassette  220  during operation. The formed volume of the paths and chambers of the cassette  220  may be slightly greater or less than the nominal constraining volume defined by the rigid constituents of the pump mechanism  130 . Practically, the firm restraints of the pump mechanism  130  permit the development of relatively high fluid pressures within the cassette  220  without significant or detrimental deformation of the cassette material. Indeed, constraining the cassette  220  over effectively the entire cassette surface creates an inherently non-compliant system. Such non-compliance contributes to the ability of the pump mechanism  130  to produce consistent, accurate volumetric fluid delivery. 
     In the preferred embodiment, the cassette pumping chambers  230   a ,  230   b  do not rest directly upon the supporting surfaces of the piston  240  and/or base  250 . Instead, a resilient material  278 , attached about the upper portion of the base  250 , operates to conform to the supporting surface of the piston assembly  210  without regard to whether the piston  240  is fully advanced, retracted or in some intermediate position. The resilient material  278  protects the pump mechanism  130  from fluid intrusion in the event any liquid is spilled on the device operational environment. The resilient material  278  also acts to further protect the cassette  220  from damage that could inadvertently occur through the operation and movement of the piston assembly  210 . 
     In an alternative embodiment, the resilient material  278  could include reinforcement means to provide additional rigidity to the resilient material  278 . As an example, reinforcement means could include a fine metal mesh or cloth embedded within the material used to fabricate the resilient material  278 . Alternatively, the resilient material  278  could include a spiral wire which is capable of concentric expansion to provide facial and lateral support for a resting cassette  220  about the interior of the base  250  (when piston  240  is in a retracted position) or about the piston  240  (when piston  240  is in an advanced position). Lastly, the material  278  could be formed of cloth altogether to eliminate any elasticity. This alternative embodiment, and its variations, could permit the use of fewer rib/splines or provide greater reliability in applications that require the piston assembly  130  to operate in larger applications, in the presence of greater fluid pressures or both. 
     Returning to  FIG. 2 , piston  240   a  is fully retracted (see also  FIG. 10 ) and piston  240   b  is fully advanced (see also  FIG. 11 ). Relative to fluid displacement, pump chamber  230   a  would be substantially full of fluid, and pump chamber  230   b  would have just expelled its contents. For the present embodiment, the pump mechanism  130  can deliver substantially continuous fluid flow through the sequential filling and expulsion of fluid from the pumping chambers  230   a ,  230   b.    
     In addition to providing substantially continuous flow, the pump mechanism  130  of the present embodiment incorporates a four-step filling protocol, which is in parallel to the expulsion of fluid from the other pump chamber, to ensure the volumetric accuracy of the delivered fluid. First, valve  288   a  is actuated and a first fluid is introduced into the pumping chamber  230   a  through the synchronized operation of the inlet valves. The pump motor  272   a  retracts a predefined amount to admit a volumetric quantity of the first fluid that, relative to the total volume of the pumping chamber  230   a , satisfies a predefined fluid mixture ratio. Second, the system tests the volumetric accuracy of the first fluid within the pump chamber  230   a . As a prelude to performing the test, valve  286   a  is actuated to occlude inlet path  228   a . The pump motor  272   a  is advanced a few steps to increase the pressure within the pumping chamber  230   a  to a predetermined level. Based upon both the relative position of the piston  240   a  and the measured chamber pressure, the fluid delivery system determines whether a sufficient quantity of fluid was delivered to the pumping chamber  230   a . Third, a second fluid is introduced into the pumping chamber  230   a  through the synchronized operation of the inlet valves. Lastly, the accuracy of the total fluid volume is tested in accordance with the procedure above. Upon determining that the pump chamber has filled properly, the fill protocol is completed. 
     As should be gained from this operational description, the piston assembly  210  reduces the opportunity for damage to blood or blood-fluid mixtures in the pumping process. Specifically, the pump assembly  210  does not possess those features that (i) facilitate the trapping of blood in or about the pumping chamber  230  or (ii) subject the blood to damaging compressive forces (roller pumps) or shearing forces (centrifugal pumps). 
     From the relationship correlating piston position to pumping chamber volume, one will appreciate that various fluids may be mixed at definable ratios through simply controlling the number of steps the pumping motors  272   a ,  272   b  move for each fill stage. As well, the total volumetric flow rate delivered by the pump mechanism  130  is dependent upon the user-defined, flow rate. 
       FIG. 12  illustrates a timing diagram for the operation of the valve cam motors  280  and  282  in conjunction with the pumping motors  272   a  and  272   b , in accordance with the prior art. In the cycle described, one chamber pumps a mixture of blood and crystalloid in a selected ratio outwardly from outlet  235  of cassette  220  ( FIG. 3 ), while the other pumping chamber is undergoing a sequential fill and test protocol. Filling chamber is filled with blood to the volume to produce the desired ratio followed by pressure testing of the chamber with its inlet and outlet valves closed to verify capture of the desired amount of blood. Following this step, the drive element of the filling pumping chamber is further retracted and crystalloid solution admitted to complete the filling of the chamber. Then the inlet and outlet valves on the filling chamber are closed to pressure test the chamber for a captured full load. Additional pressure tests and monitoring may be conducted during pumping to determine if there is any unsafe occlusion or to control the pressure within an appropriate safe range for a given procedure. 
     Thus, at the commencement of the  FIG. 12  diagram, the pumping chamber bladder  230   a  has been emptied, and the other bladder  230   b  is full of a blood-crystalloid mixture in the desired proportions. The outlet valve  288   a , from chamber  230   a  is closed. Outlet valve  288   b  is open to pass the combined fluid from chamber  230   b  through the outlet  235  to the heat exchanger  131  ( FIG. 1 ) at the requested volumetric flow rate. Throughout the period of delivery from chamber  230   b , its inlet valve  286   b  remains closed, and the corresponding piston  240   b  is advanced by motor  272   b  to reduce the volume of bladder  230   b  to expel the blood/crystalloid solution. The speed of motor  272   b  is governed by the requested flow rate. The outlet valve  288   a  from chamber  230   a  remains closed throughout this period of pumping from chamber  230   b.    
     The valves  284   a  and  284   b  controlling inlet of blood and crystalloid to common inlet path  226 , and the inlet valve for chamber  230   a  (inlet valve  286   a ) are sequentially opened and closed during the filling protocol for bladder  230   a , which occupies the time period during which bladder  230   b  is delivering fluid to line  128  ( FIG. 1 ). Thus, when one bladder has completed its pumping step, the other has received solution constituents in the desired ratio and is ready to deliver. Substantially continuous flow is thus enabled, as shown at the top of  FIG. 12 . 
     In the 4-step filling protocol for chamber  230   a , illustrated at the outset of the diagram, valves  284   a  and  286   a  are initially open, and valve  284   b  closed. Thus, an open flow path for entry of blood to chamber  230   a  is provided through inlet  222 , common inlet path  226 , and pump chamber inlet path  228   a , while crystalloid is occluded at valve  284   b . Pump motor  272   a  (shown in  FIG. 2 ) is retracted sufficiently to admit sufficient blood to comprise the desired fraction of total chamber volume. Then valves  284   a  and  286   a  are closed, and pump motor  272   a  is advanced a few steps, to confirm by elevating pressure that the requested blood load has been captured between closed valves  286   a  and  288   a . With confirmed introduction of the correct amount of blood, valves  286   a  and  284   b  are opened while valve  284   a  remains closed to stop further blood entry. Pump motor  272   a  now retracts to admit the correct volume of crystalloid along paths  225 ,  226  and  228   a . This is followed by closing valves  286   a  and  284   b . Motor  272   a  is advanced briefly to confirm by pressure elevation that the full incremental volume has been occupied by crystalloid solution. With this confirmation, the fill protocol is complete, and chamber  230   a  is ready for delivery on the completion of delivery from chamber  230   b . As chamber  230   a  then delivers, chamber  230   b  undergoes a similar 4-step filling protocol. 
     The total volumetric flow rate from the cassette is varied pursuant to operator request simply by compressing or expanding the time for a cycle to be completed. Of course, if intermittent operation is desired, this may be provided as well. No matter what changes may be made to the blood/crystalloid flow rate, microprocessor  146  preferably automatically controls potassium pump  132  to deliver at a concentration which provides the requested potassium concentration. 
     Turning now to  FIG. 13 , a timing diagram illustrating the operation of a preferred embodiment of the present invention in a pulsatile flow mode is depicted. In a preferred embodiment, because spline pistons are utilized, the flow rate of the fluid leaving the pumping chamber is related quadratically to the velocity of the piston. To achieve a pulsatile flow, the velocity of the piston is varied cyclically. Period  302  represents this cyclic flow characteristic. While the slopes of  310   a ,  310   b , and  310   c  appear substantially equal, it is likely that the actual slope would be steeper for  310   b  and  310   c  due to the non-linear nature of the surface area of the piston being applied to the fluid pouch as the piston is advanced. 
     Period  302  comprises partial-cycles  308   a ,  308   b ,  308   c  during which the piston is moved at a lower velocity, so as to achieve a lower flow rate. During partial-cycles  310   a ,  310   b ,  310   c  the piston is moved at a higher velocity, thus achieving a higher flow rate. The portion of period  302  during which the higher velocity is applied is referred to as the “duty cycle”. This velocity characteristic (which also represents the instantaneous flow rate) is a square- or rectangle-wave. Due to compliance in the tubing connecting the cardioplegia delivery system to the patient, the actual flow rate characteristic and actual fluid pressure characteristic experienced by the patient is more sinusoidal in nature, as shown at the top of  FIG. 13 . It should also be noted that the flow rate(s) so obtained have the desirable property of being independent of the fluid pressure of the fluid being pumped. A desirable fluid pressure, for physiological purposes, is within the range of 50-250 mmHg. 
     The upper and lower velocities, corresponding to upper and lower flow rates, respectively, are selected so as to achieve a desired average flow rate over time given a particular amplitude and duty cycle for the pulsatile flow. The difference in pressure obtained during the upper flow rate and that obtained during the lower flow rate is called the “pulse pressure.” An operator may also specify a particular frequency, corresponding to a simulated heart rate, at which the operator wishes the pulsatile flow to run. In order to simulate normal physiological conditions, a frequency of between 50-90 beats per minute is typically used. As shown in  FIG. 13 , the position of the piston varies at a low rate of change  308  during the low-velocity portions of period  302 , while the position changes at a higher rate  310  during the high-velocity portions of period  302 . Although the instantaneous velocity of the piston, and hence the instantaneous flow rate of the fluid being pumped, changes from instant-to-instant, the average rate of flow over time is a constant and is the same as would be achieved using a non-pulsatile flow. 
     Given a desired average flow rate, a desired amplitude, and a desired duty cycle, the microprocessor control of a preferred embodiment of the present invention calculates an appropriate upper and lower flow rate.  FIG. 14  is a flowchart representation of a process of computing these upper and lower flow rates in a preferred embodiment of the present invention. First, the desired average flow rate (expressed in mL/min.), a desired amplitude (representing the desired magnitude of the upper flow rate as expressed as a percentage of the average flow rate), and a duty cycle (expressed as a percentage of a given cycle to be spent at the upper flow rate) are provided by the user (block  400 ). In a preferred embodiment, the amplitude may range from 50% to 300%, and the duty cycle may range from 10% to 50%. Next, the appropriate upper flow rate is calculated from the amplitude, as (1+Amplitude)×Avg. flow rate (block  402 ). 
     For safety purposes, one embodiment of the present invention supports a maximum upper flow rate of 750 mL/min. Therefore, if the upper flow rate calculated in block  402  exceeds 750 mL/min (block  404 :Yes), then the upper flow rate is set to 750 mL/min. Then the amplitude is adjusted to be 750 mL/min./Avg. flow rate (block  406 ), and the process cycles back to block  408 . The lower flow rate is calculated as 
               (     1   +       Duty   ⁢           ⁢   cycle   ×   Amplitude         Duty   ⁢           ⁢   cycle     -   1         )     ×     Avg   .           ⁢   flow     ⁢           ⁢   rate   ⁢           ⁢       (     block   ⁢           ⁢   408     )     .           
If this lower flow rate is less than 10 mL/min. (block  410 : Yes), the lower flow rate is set to 10 ml/min. Then the amplitude is adjusted to be
 
                 (       10   -       Avg   .           ⁢   flow     ⁢           ⁢   rate           Avg   .           ⁢   flow     ⁢           ⁢   rate       )     ×     (         Duty   ⁢           ⁢   cycle     -   1       Duty   ⁢           ⁢   cycle       )     ⁢     (     block   ⁢           ⁢   412     )       ,         
and the process cycles back to block  414 .
 
     If the lower flow rate is greater than the minimum value of 10 mL/min. (block  410 :No), then a cyclic flow profile, such as that depicted in  FIG. 13  is commenced, in which the velocity of the piston, and hence the instantaneous flow rate of the fluid delivered to the patient, cycles between the calculated upper and lower flow rates, according to the prescribed duty cycle and frequency (block  414 ). 
     One of the preferred implementations of the invention is a client application, namely, a set of instructions (program code) or other functional descriptive material in a code module that may, for example, be resident in the random access memory of a microprocessor, microcontroller, or other computer (e.g., microprocessor control section  146  in  FIG. 1 ). Until required by the computer, the set of instructions may be stored in another computer memory, for example, in a hard disk drive, or in a removable memory such as an optical disk (for eventual use in a CD ROM) or floppy disk (for eventual use in a floppy disk drive), or downloaded via the Internet or other computer network. Thus, the present invention may be implemented as a computer program product for use in a computer. In addition, although the various methods described are conveniently implemented in a general purpose computer selectively activated or reconfigured by software, one of ordinary skill in the art would also recognize that such methods may be carried out in hardware, in firmware, or in more specialized apparatus constructed to perform the required method steps. Functional descriptive material is information that imparts functionality to a machine. Functional descriptive material includes, but is not limited to, computer programs, instructions, rules, facts, definitions of computable functions, objects, and data structures. 
     While particular embodiments of the present invention have been shown and described, it will be obvious to those skilled in the art that, based upon the teachings herein, changes and modifications may be made without departing from this invention and its broader aspects. Therefore, the appended claims are to encompass within their scope all such changes and modifications as are within the true spirit and scope of this invention. Furthermore, it is to be understood that the invention is solely defined by the appended claims. It will be understood by those with skill in the art that if a specific number of an introduced claim element is intended, such intent will be explicitly recited in the claim, and in the absence of such recitation no such limitation is present. For non-limiting example, as an aid to understanding, the following appended claims contain usage of the introductory phrases “at least one” and “one or more” to introduce claim elements. However, the use of such phrases should not be construed to imply that the introduction of a claim element by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim element to inventions containing only one such element, even when the same claim includes the introductory phrases “one or more” or “at least one” and indefinite articles such as “a” or “an;” the same holds true for the use in the claims of definite articles.

Technology Classification (CPC): 5