Mechanical circulatory support using ventricular assist

Transcription

1 Evaluation of a Pulsatile Pediatric Ventricular Assist Device in an Acute Right Heart Failure Model Dominique Shum-Tim, MD, Brian W. Duncan, MD, Victor Hraska, MD, Ingeborg Friehs, MD, Toshiharu Shin oka, MD, and Richard A. Jonas, MD Department of Cardiovascular Surgery, Children s Hospital and Harvard Medical School, Boston, Massachusetts Background. The development of pulsatile ventricular assist devices for children has been limited mainly by size constraints. The purpose of this study was to evaluate the MEDOS trileaflet-valved, pulsatile, pediatric right ventricular assist device (stroke volume 9 ml) in a neonatal lamb model of acute right ventricular failure. Methods. Right ventricular failure was induced in ten 3-week-old lambs (8.6 kg) by right ventriculotomy and disruption of the tricuspid valve. Control group 1 (n 5) had no mechanical support whereas experimental group 2(n 5) had right ventricular assist device support for 6 hours. The following hemodynamic parameters were measured in all animals: heart rate and right atrial, pulmonary arterial, left atrial, and systemic arterial pressures. Cardiac output was measured by an electromagnetic flow probe placed on the pulmonary artery. Results. All results are expressed as mean standard deviation and analyzed by Student s t test. A p value less than 0.05 was considered statistically significant. Baseline measurements were not significantly different between groups and included systemic arterial pressure, mm Hg; right atrial pressure, mm Hg; mean pulmonary arterial pressure, mm Hg; left atrial pressure, mm Hg; and cardiac output, L/min. Right ventricular injury produced hemodynamics compatible with right ventricular failure in both groups: mean systemic arterial pressure, mm Hg; right atrial pressure, mm Hg; left atrial pressure, mm Hg; and cardiac output, L/min. All group 1 animals died at a mean of minutes after the operation. All group 2 animals survived the duration of study. Hemodynamic parameters were recorded at 2, 4, and 6 hours on and off pump, and were significantly improved at all time points: mean systemic arterial pressure, mm Hg; right atrial pressure, mm Hg; left atrial pressure, mm Hg; and cardiac output, L/min. Conclusions. The results demonstrate the successful creation of a right ventricular failure model and its salvage by a miniaturized, pulsatile right ventricular assist device. The small size of this device makes its use possible even in small neonates. (Ann Thorac Surg 1997;64: ) 1997 by The Society of Thoracic Surgeons Mechanical circulatory support using ventricular assist devices (VAD) has become standard in adult patients with cardiac failure refractory to pharmacologic therapy. A variety of devices have been used as a bridge to recovery of ventricular function or cardiac transplantation with acceptable morbidity and mortality [1 5]. Infants and small children who experience profound ventricular dysfunction, however, have fewer treatment options for mechanical circulatory support. The development of a pulsatile VAD for children has been limited by size constraints and the requirement of multiple pumps with different volumes to accommodate a wide range of pediatric sizes. In addition, children are more likely to experience pulmonary and biventricular failure than pure left ventricular dysfunction as seen in adults with Presented at the Thirty-third Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Feb 3 5, Address reprint requests to Dr Jonas, Department of Cardiovascular Surgery, Children s Hospital, 300 Longwood Ave, Boston, MA coronary artery disease. These factors and the familiarity of many pediatric centers with the use of extracorporeal membrane oxygenation have led to its widespread use of mechanical circulatory support in children. There are several potential advantages that a pulsatile VAD, designed specifically for children, would provide. The lack of an oxygenator would simplify the circuit and reduce blood cell trauma. Such a device would ideally provide pulsatile flow with a range of pump volumes capable of supporting small neonates through adolescents. The MEDOS-HIA VAD system (MEDOS-Helmholtz Institute, Aachen, Germany) provides pulsatile circulatory support with a pump size as small as 9 ml. The pump uses a pneumatically driven diaphragm, with two trileaflet polyurethane inlet and outlet valves [6]. This system can be used for right ventricular assist device (RVAD), left ventricular assist device, or biventricular assist device support. The present report describes the use of this system as an RVAD in a pediatric model of acute right ventricular (RV) failure by The Society of Thoracic Surgeons /97/$17.00 Published by Elsevier Science Inc PII S (97)

2 Ann Thorac Surg SHUM-TIM ET AL 1997;64: PEDIATRIC VAD IN RIGHT VENTRICULAR FAILURE 1375 Material and Methods Anesthesia and Instrumentation All animals received humane care in compliance with the Principles of Laboratory Animal Care formulated by the National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals prepared by the National Academy of Sciences and published by the National Institutes of Health (NIH Publication 85-23, revised 1985). The experimental protocol was approved by the institutional review board on animal experimentation at the Children s Hospital, Boston (approval number: A ). Three-week-old lambs (average weight, kg) were used for the following studies. All animals were sedated with intramuscular ketamine hydrochloride (50 mg/kg), then intubated and mechanically ventilated. Anesthesia was maintained with intravenous fentanyl (30 g kg 1 h 1 ), and midazolam (0.3 mg kg 1 h 1 ). Body temperature was maintained between 37.5 to 38.0 C using a warming blanket and heat lamp. Catheters were inserted into the femoral artery and vein for blood sampling, fluid infusion, and monitoring of systemic arterial pressure. The femoral venous line was advanced into the right atrium (RA) for RA pressure monitoring. A median sternotomy was then performed and the main pulmonary artery (PA) and left atrial (LA) appendage were catheterized for pressure monitoring. An electromagnetic flow probe (MFV-3200; Nihon Kohden Corp, Tokyo, Japan) was placed around the distal main PA to record the cardiac output at baseline, and at 10-minute time points after the induction of RV failure in all animals. The flow probe was removed from the PA and placed in-line with the outflow cannula for group 2 animals supported by RVAD (see below). Device The MEDOS HIA-VAD is a pneumatically driven pulsatile blood pump (Fig 1). The disposable blood pump incorporates a multilayered diaphragm that separates the blood flow chamber from the pneumatic drive chamber of the device. There are two integral trileaflet, polyurethane valves at the inflow and outflow connectors. The pumps, when used as left ventricular assist devices, are available in various sizes with stroke volumes of 10, 25, 60, and 80 ml. For RVAD, there is a 10% reduction in stroke volume for each corresponding pump size (9, 22.5, 54, and 72 ml, respectively) that was found to be optimal in a right left ventricular output balance. The stroke volume employed for this study was 9 ml. The polyurethane pumps are pneumatically activated by an integrated driving system that consists of a solid-state electronic control console with digital readout. The control console allows adjustment of pulse rate, drive pressure, and percentage systole to optimize hemodynamics. The system can be triggered by the electrocardiogram for operation in a synchronous mode to provide counterpulsation. The device was operated in asynchronous mode during this study. The second component of the MEDOS Fig 1. (A) The MEDOS HIA-VAD system consists of pneumatically driven polyurethane blood pumps. Pumps with stroke volumes of 10, 25, and 60 ml are shown (clockwise from top). (B) Top: Integrated control unit with touch screen monitor for the MEDOS HIA-VAD. Bottom: Internal power supply unit and pneumatic compressor and vacuum. drive system is an electrically powered internal pneumatic compressor and vacuum. Right Ventricular Injury and Hemodynamic Measurements Acute RV failure was surgically induced in group 1 animals (n 5) without subsequent mechanical circulatory assistance. In group 2 (n 5) animals, RV support using the MEDOS HIA-VAD was instituted after the completion of RV injury. The RVAD was maintained for 6 hours after injury until the experiment was electively terminated. After placement of monitoring lines and recording of baseline parameters, all animals were fully heparinized (300 U/kg). A 14F arterial cannula (DLP, Inc, Grand Rapids, MI) was inserted into the main PA and secured

3 1376 SHUM-TIM ET AL Ann Thorac Surg PEDIATRIC VAD IN RIGHT VENTRICULAR FAILURE 1997;64: Table 1. Hemodynamic Parameters in Groups 1 and 2 at Baseline, After Right Ventricular Injury, and On and Off RVAD Time Point Mean SAP Mean RAP Mean PAP Mean LAP CO (L/min) PVR (mm Hg min/l) HR (beat/min) Group 1 baseline min after injury a a a a a a a Group 2 baseline min after injury a a a a a a a 10 min RVAD on b b b b b h RVAD on h RVAD off b b b b h RVAD on h RVAD off b b b b h RVAD on h RVAD off b b b b a p 0.05 versus baseline. b p 0.05 RVAD on versus off. CO cardiac output; HR heart rate; LAP left atrial pressure; PAP pulmonary arterial pressure; PVR pulmonary vascular resistance; RAP right atrial pressure; RVAD right ventricular assist device; SAP systemic arterial pressure. with pursestring sutures. This PA cannula allowed blood transfusion in all animals and provided outflow cannulation for RVAD-supported group 2 animals. A patent foramen ovale, which was invariably present in lambs at this age, was closed primarily with inflow occlusion. A ventriculotomy was then performed along the RV outflow tract. Through this incision, the tricuspid valve was disrupted by division of all chordal attachments. Lethal RV injury was reliably produced by right ventriculotomy and tricuspid regurgitation. After the induction of RV failure, the absence of right-to-left shunting at the atrial level was confirmed by measurement of RA and LA blood gases. For animals supported by RVAD, a 24F right-angled cannula (Polystan, Varlose, Denmark) was inserted through the RA appendage. The RVAD settings were adjusted to reestablish baseline cardiac output and systemic pressure. Hemodynamic parameters were recorded after 10 minutes of stabilization after injury in all animals. Hemodynamic measurements were repeated every 2 hours for 6 hours in group 2 animals with RVAD support. During the measurement period, the RVAD was turned off for 5 minutes. In this way, each animal served as its own control for hemodynamic measurements on and off RVAD. Pulmonary vascular resistance (PVR in mm Hg min/l) was calculated by the following equation: (mean PA pressure mean LA pressure)/cardiac output. Statistical Analysis All values are expressed as the mean standard deviation. The baseline and postinjury values were compared within and between groups by the paired and unpaired Student s t tests, respectively. Subsequent serial measurements of all parameters between assisted and nonassisted modes in the same animals were compared by paired t test. Differences were considered statistically significant when the p value was less than Results Baseline Hemodynamics The following baseline hemodynamic parameters were recorded in groups 1 and 2 before RV injury: mean systemic arterial pressure, heart rate, RA pressure, mean PA pressure, LA pressure, and mean PA cardiac output (CO). The PVR was calculated for each animal. Baseline measurements are summarized in Table 1. Effect of Right Ventricular Injury Right ventriculotomy and surgically induced tricuspid regurgitation resulted in lethal acute RV failure. Severe RV dysfunction developed in both groups, characterized by systemic hypotension, increased RA pressure, decreased LA pressure and decreased CO (Table 1; Fig 2). All the animals in control group 1 died at a mean period of minutes after surgery. The RVAD-supported group 2 hemodynamics were not significantly different from control group 1 after RV injury. All group 2 animals survived the 6 hours of planned RVAD support. Effect of Right Ventricular Assist Device on Right Ventricular Failure Institution of RVAD resulted in significant improvements in all hemodynamic parameters. The hemodynamic effects of RVAD support for group 2 animals are summarized in Table 1 and illustrated in Figures 3 through 9. Hemodynamic values shown reflect the mean values for all group 2 animals on full RVAD support compared with the mean values obtained from the same animals with the device off for 5 minutes at the 2-, 4-, and 6-hour time points after RV injury. With the initial RV injury, expected decreases were observed in mean systemic arterial pressure (Fig 3), LAP (Fig 4), and CO (Fig 5). Right atrial pressure increased significantly (Fig 6). All hemodynamic parameters were subsequently normalized by RVAD support as demonstrated. Values for CO off RVAD are demonstrated only

4 Ann Thorac Surg SHUM-TIM ET AL 1997;64: PEDIATRIC VAD IN RIGHT VENTRICULAR FAILURE 1377 Fig 2. Hemodynamic measurements after acute right ventricular failure in the control group were characterized by significantly elevated right atrial (RA) pressure (A), as well as significant decreases in systemic pressure (B), left atrial (LA) pressure (C), and cardiac output (D). at 10 minutes. As described above, in group 2 animals the CO flow probe was removed from the PA and placed in-line with the outflow cannula after measuring baseline hemodynamics because of size constraints. Severe tricuspid insufficiency was demonstrated by a dramatic increase in mean RA pressure with a pulsatile waveform in all animals. The mean pulse pressure of the RA increased from a baseline of mm Hg to mm Hg (p 0.048) immediately after the induction of RV injury (Fig 7). The mean RA pressure was rapidly reduced and the pulsatility of the waveform was obliterated by the onset of RVAD. These hemodynamic characteristics were maintained throughout the duration of study. On termination of mechanical support, the animals in group 2 survived for minutes (NS versus group 1). The PA pressure was observed to increase immediately after the surgical insult to the RV (Fig 8), accompanied by an increase in the calculated PVR in all animals (Fig 9). These changes in PA pressure and PVR normalized after Fig 3. Normalization of systemic mean arterial pressure in group 2 was maintained for 6 hours by the MEDOS HIA right ventricular assist device (RVAD). Fig 4. Left atrial (LA) filling pressure was significantly reduced by right ventricular failure and effectively normalized by the institution of right ventricular assist device (RVAD) support.

5 1378 SHUM-TIM ET AL Ann Thorac Surg PEDIATRIC VAD IN RIGHT VENTRICULAR FAILURE 1997;64: Fig 5. Low cardiac output induced by acute right ventricular failure was reversed by the pulsatile MEDOS HIA right ventricular assist device (RVAD) system. 2 hours of circulatory support. Initial increases in PA pressure probably represent the animals response to rapid transfusion, inflow occlusion, and catecholamine surge associated with the surgical procedure. Elevations in the calculated PVR were magnified by accompanying decreases in LA pressure and CO. Comment A variety of mechanical circulatory assist devices have been successfully employed for adults with severe ventricular dysfunction [1 5]. Intraaortic balloon counterpulsation as well as VADs from several different manufacturers are currently available. The effectiveness of intraaortic balloon pumping is limited in pediatric patients because of their increased aortic elasticity, rapid heart rates with small stroke volumes, and technical difficulties related to insertion in small femoral vessels [7]. The development of VAD for pediatric patients has been limited by size constraints and differences in the pathophysiology of cardiac failure in children. A pulsatile pediatric VAD requires multiple pump sizes to provide stroke volumes in the range of patients from newborns to young adults. In contrast to predominant left ventricular failure secondary to coronary artery disease in adults, Fig 7. Evidence of severe tricuspid regurgitation after surgical induction of right ventricular failure was shown by significantly elevated right atrial (RA) pulse pressure compared with baseline value. Note the effect of the right ventricular assist device (RVAD) in ameliorating the hemodynamic characteristics of severe tricuspid regurgitation. children are more likely to demonstrate right ventricular, biventricular, and pulmonary failure. These factors, in addition to the favorable experience in treating lifethreatening pulmonary conditions in children, have led to the widespread use of extracorporeal membrane oxygenation for cardiac support in many pediatric centers [8, 9]. However, the complexity of the extracorporeal membrane oxygenation circuitry with the presence of an oxygenator requires increased anticoagulation, larger priming volume, and produces more blood cell trauma. For these reasons, extracorporeal membrane oxygenation may not always be the optimal methodology for prolonged circulatory support in pediatric patients. These potential disadvantages also limit its application intraoperatively and in the early postoperative period. In addition, pulsatile flow might confer advantages for endorgan preservation during long-term support. The MEDOS HIA-VAD system provides pulsatile circulatory support with pumps available in a variety of stroke volumes to accommodate newborn to adult pa- Fig 6. Significant reduction of the elevated mean right atrial (RA) pressure after right ventricular injury in group 2 was observed after the onset of right ventricular assist device (RVAD) use. Fig 8. After the right ventricular injury, there was a transient elevation of mean pulmonary arterial (PA) pressure, possibly secondary to reactive pulmonary vasoconstriction after surgical injury. Significant reduction of pulmonary blood flow characterized by reduction of mean PA pressure was observed after 2 hours when the right ventricular assist device (RVAD) was turned off. The use of the RVAD reestablished the increased PA pressure.

6 Ann Thorac Surg SHUM-TIM ET AL 1997;64: PEDIATRIC VAD IN RIGHT VENTRICULAR FAILURE 1379 Fig 9. Pulmonary vascular resistance (PVR) was acutely elevated by the surgical procedure of inflow occlusion, blood transfusion, and reduced left-sided pressure. The right ventricular assist device (RVAD) partially offset this elevated PVR and maintained it at the same level throughout the 6-hour period of experiment. (LAP left atrial pressure; PAP pulmonary arterial pressure.) tients. The circuit is simple, with the disposable blood pump connected directly to the inflow and outflow cannulas. This minimizes the surface area of blood contact and reduces priming volumes. The priming volume for the circuit in this study, using the 9-mL blood pump, was less than 20 ml. Removal of air from the device is facilitated by its transparent design. Two trileaflet polyurethane valves integrated into the device have been shown to result in excellent hemodynamic properties and minimal hemolysis with low thrombogenicity [10 12]. Because of the simplicity of the circuit, setup can be performed within minutes in an emergency situation. Furthermore, the simple circuit with its self-contained power console minimizes intensive surveillance by personnel, and facilitates transportation of patients during support. In this study, we created an acute pediatric model (lambs 10 kg) of RV failure. The surgical technique was a combination of those reported in larger animals [13 15]. This model created RV dysfunction by making a right ventriculotomy and disrupting the tricuspid valve. The RV failure produced was progressive and rapidly fatal without mechanical assistance. The MEDOS HIA-VAD system employed as an RVAD was able to normalize systemic arterial pressure and CO while reducing the dramatically elevated RA filling pressure seen in this model. In contrast to previous studies employing RV apical cannulation, the insertion of RVAD itself did not accelerate RV dysfunction [14]. All the experimental animals in group 2 survived for a mean of minutes after the discontinuation of RVAD support, which was not significantly different from the survival time of the control group 1. The absence of deterioration of RV function in this report may reflect RA cannulation rather than RV apical cannulation in the previous study. The benefits of pulsatile circulatory support have not been unequivocally demonstrated [16, 17]. In addition, good clinical outcomes have been reported using nonpulsatile VADs [18, 19]. Yet, subtle physiologic differences have been suggested. In the pulmonary circulation, elevated PVR and increased lung water content have been shown experimentally during nonpulsatile circulatory support [20 22]. The present study did not address the potential benefits conferred by pulsatile circulatory assistance. We are currently using the MEDOS HIA-VAD for long-term support in a model of left ventricular failure to examine these issues. There are several points of limitation that merit further discussion. First, this study represents an acute model to assess the feasibility and reliability of the pulsatile pediatric RVAD. The long-term effects of this device remain to be evaluated and further investigations are underway in our laboratory. Second, the current protocol used full anticoagulation simulating the clinical situation of RVAD support after cardiopulmonary bypass. In addition, we used heparinized fresh blood transfusion obtained from another donor lamb for the creation of RV injury. Therefore, the anticoagulation regimen and hematologic effects of this device could not be evaluated by this particular study. In conclusion, there is currently no pulsatile VAD available in the United States for pediatric patients, although this device has been used successfully in children in Europe [23]. The ability to supply pulsatile circulatory assistance for a range of patient sizes from small newborns to young adults makes this a potentially valuable system. This initial in vivo study demonstrates the ability of the pulsatile MEDOS HIA-VAD to maintain satisfactory hemodynamics in a pediatric lamb model of acute RV failure. References 1. Pae WE, Miller CA, Matthews Y, Pierce WS. Ventricular assist devices for postcardiotomy cardiogenic shock. J Thorac Cardiovasc Surg 1992;104: Chen JM, Levin HR, Rose EA, et al. Experience with right ventricular assist devices for perioperative right-sided circulatory failure. Ann Thorac Surg 1996;61: Champsaur G, Ninet J, Vigneron M, Cochet P, Neidecker J, Boissonnat P. Use of the Abiomed BVS system 5000 as a bridge to cardiac transplantation. J Thorac Cardiovasc Surg 1990;100: Pennington DG, Samuels LD, Williams G, et al. Experience with the Pierce-Donachy ventricular assist device in postcardiotomy patients with cardiogenic shock. World J Surg 1985; 9: Buckley MJ, Craver JM, Gold HK, Mundth ED, Daggett WM, Austen WG. Intra-aortic balloon pump assist for cardiogenic shock after cardiopulmonary bypass. Circulation 1973; 47,48(Suppl 3): Knierbein B, Rosarius N, Reul H, Rau G. New methods for the development of pneumatic displacement pumps for cardiac assist. Int J Artif Organs 1990;13: Del Nido PJ, Swan PR, Benson LN, et al. Successful use of intra-aortic balloon pumping in a 2-kilogram infant. Ann Thorac Surg 1988;46: Del Nido PJ. Extracorporeal membrane oxygenation for cardiac support in children. Ann Thorac Surg 1996;61: Klein MD, Shaheen KW, Whittlesey GC, et al. Extracorporeal membrane oxygenation for the circulatory support of children after repair of congenital heart disease. J Thorac Cardiovasc Surg 1990;100: Eilers R, Harbott P, Reul H, Rakhorst G, Rau G. Design improvements of the HIA-VAD based on animal experiments. Artif Organs 1994;18: Rakhorst G, Hensens AG, Verkerke GJ, et al. In-vivo evaluation of the HIA-VAD : a new German ventricular assist device. Thorac Cardiovasc Surg 1994;42:

7 1380 SHUM-TIM ET AL Ann Thorac Surg PEDIATRIC VAD IN RIGHT VENTRICULAR FAILURE 1997;64: Reul H, Taguchi K, Herold M, et al. Comparative evaluation of disk and trileaflet valves in left ventricular assist devices. Int J Artif Organs 1988;11: Jett KG, Applebaum RE, Clark RE. Right ventricular assistance for experimental right ventricular dysfunction. J Thorac Cardiovasc Surg 1986;92: Jett KG, Picone AL, Clark RE. Circulatory support for right ventricular dysfunction. J Thorac Cardiovasc Surg 1987;94: Fischer SIC, Willshaw P, Armentano RL, Delbo MIB, Pichel RH, Favaloro RG. Experimental acute right ventricular failure and right ventricular assist in the dog. J Thorac Cardiovasc Surg 1985;90: Sakaki M, Teanaka Y, Tatsumi E, Nakatani T, Takano H. Influences of nonpulsatile pulmonary flow on pulmonary function: evaluation in a chronic animal model. J Thorac Cardiovasc Surg 1994;108: Reddy RC, Goldstein AH, Pacella JJ, Cattivera GR, Clark RE, Magovern GJ Sr. End organ function with prolonged nonpulsatile circulatory support. ASAIO J 1995;41:M Karl TR, Sano S, Horton S, Mee RBB. Centrifugal pump left heart assist in pediatric cardiac operations: indications, technique, and results. J Thorac Cardiovasc Surg 1991;102: Louis PT, Bricker JT, Frazier OH, et al. Nonpulsatile total left ventricular support in pediatric patients. Crit Care Med 1992;20: Raj JU, Kaapa P, Anderson J. Effect of pulsatile flow on microvascular resistance in adult rabbit lungs. J Appl Physiol 1992;72: Clarke PC, Kahn DR, Dufek JH, Sloan H. The effects of nonpulsatile blood flow on canine lungs. Ann Thorac Surg 1968;6: Richenbacher WE, Pierce WS, Jurmann M, et al. Pulmonary vascular effects of pulsatile and nonpulsatile mechanical right ventricular assistance. Surg Forum 1989;40: Konertz W, Hotz H, Schneider M, Redlin M, Reul H. Clinical experience with the MEDOS HIA-VAD system in infants and children: a preliminary report. Ann Thorac Surg 1997;63: DISCUSSION DR DUKE E. CAMERON (Baltimore, MD): Could you tell us a little more about the device itself? DR SHUM-TIM: This device is made in Germany, where they have already used it in both adult and pediatric populations. It is constructed of polyurethane to increase its biocompatibility. It has been extensively studied with respect to the design both in vivo and in vitro to optimize its flow characteristics, biocompatibility, and durability. It is a user-friendly device as far as our experience in the laboratory. We have not used it clinically yet, but I do not think there is any pulsatile device available for the pediatric population in the United States. DR CAMERON: But what is the range in stroke volume? DR SHUM-TIM: They have different sizes that are 10, 25, 60, and 80 ml available in the left ventricular side. With respect to the RVAD, there s a 10% reduction for each corresponding volume. DR EDWARD A. PASCOE (Winnipeg, Manitoba, Canada): The pulsatile nature of the support is intriguing in view of the suggested potential for brain protection with pulsatile flow in clinical open heart surgery. In this experimental model, do you have any data to suggest whether this assist device would have been any more or less supportive had it been a centrifugal pump with nonpulsatile flow? DR SHUM-TIM: Well, clearly this study was not aimed to address this issue. It s a very controversial issue with respect to pulsatile versus nonpulsatile support. Clinical reports have shown that nonpulsatile VADs have been effective and resulted in very good outcome. There are some subtle physiologic benefits demonstrated by experimental studies, however, using pulsatile support. This is especially true when prolonged support is used. As a matter of fact, we are trying to establish a long-term model using this system as an LVAD support to try to resolve some of these issues. DR CAMERON: Can the device be gated to the electrocardiogram so that it could counter-pulse? DR SHUM-TIM: Yes. That is right. Each of these consoles can run two devices simultaneously and independently. They could be run either synchronously or asynchronously with the electrocardiogram. DR CAMERON: One of the concerns I have with the model is that it induces severe tricuspid regurgitation, which prevents distention of the ventricle, which is usually one of the compounding problems of ventricular support. DR SHUM-TIM: Here, we were aiming to create a fatal right ventricular failure model. We have achieved this by surgically inducing severe tricuspid regurgitation and, effectively, a common chamber between the right ventricle and right atrium. Our results have shown that the right atrial, and therefore, the right ventricular pressure were actually very well decompressed by the current device. This demonstrated its ability to potentially prevent ventricular distention in the absence of aortic regurgitation. But again, it is not a real clinical situation. In most of the clinical situations, you do not have a wide-open tricuspid regurgitation like that. Your point is, however, very well taken. DR AKIF ÜNDAR (San Antonio, TX): I just want to make a couple of comments about pulsatile flow. Although controversy still exists, pulsatile flow has many advantages over nonpulsatile perfusion. This has been clearly proven in humans and animals by several investigators. Doctor John Murkin has clearly shown that the use of pulsatile perfusion was related to significantly fewer complications and deaths compared with nonpulsatile perfusion in 316 patients. In contrast, there have been several articles in the literature showing no difference between both types of perfusion. However, the investigators who are proponents of nonpulsatile have never shown that the use of nonpulsatile perfusion has any benefits over pulsatile flow. They have only noted that they could not find any differences between pulsatile and nonpulsatile flow. What is pulsatile flow? Showing a pulse pressure more than 20 mm Hg is not enough. Investigators should agree on common criteria for pulsatile flow, and then comparisons using these criteria will make more sense for different institutions results. We believe that pulsatile flow must be physiologic. In addition to the pulse pressure, ejection time, stroke volume, and dp/dt should be mentioned in the publications. Unfortunately, most of the pulsatile pumps currently available do not produce physiologic waveforms.