Advances in technology and increased clinical need have led to the development of a new type of blood pump. The Jarvik 2000 Heart is an electrically powered, axial-flow left ventricular assist device that has been developed during the past 13 years. Unlike first-generation left ventricular assist devices, which were developed in the 1970s and were designed to totally capture the cardiac output, the Jarvik 2000 is designed to normalize the cardiac output by augmenting the function of the chronically failed heart for extended periods. Design iterations have been tested in 67 animals, and clinical trials have recently begun. Three patients have received the Jarvik 2000 as a bridge to transplantation, and 1 patient is being supported permanently outside the hospital. All 4 patients have improved from New York Heart Association functional class IV to class I, and 2 of them have been discharged from the hospital after heart transplantation. The experimental and clinical results indicate that the Jarvik 2000 can provide physiologic support with minimal complications and is reliable, biocompatible, and easy to implant.

The AbioCorTM was implanted in a 6-month old male calf. The internal components of the AbioCorTM consist of the thoracic unit, the electronic controller with a radio frequency communication, a rechargeable battery, and the secondary coil of a transcutaneous energy transmission device (TET). The primary coil of the TET was placed externally over the secondary coil. A computer console was used to display physiologic pressures as well as telemetric data from the implanted controller. Physiologic parameters monitored included AoP, LAP, PAP, and CVP. Device parameters recorded included beat rate, hydraulic pressures, voltage, current, power, and internal temperatures of the implanted components. Over the 12-week implant period the CO was maintained around 9 L/min, near the systems maximum output. The mean AoP, LAP, and SVC were 100±13 mmHg, 19±5 mmHg, and 18±5 mmHg respectively. The animal underwent five instrumented treadmill studies. PvO2 reduction was observed due to increased metabolic demand. Throughout the study hemoglobin and hematocrit were 9.9±1.6 mg/dL and 29.6±5.2% respectively. The plasma free hemoglobin was 3.1±1.9 mg/dL and was within normal limits. Antibiotic therapy was given during the last three weeks due to positive blood cultures secondary to indwelling monitoring catheters. Otherwise, infection was not a complicating factor. Pathology demonstrated no gross evidence of thromboembolic events. Liver congestion was evident due to increasing growth-driven cardiac need of the animal exceeding the maximum device output. Although long term (12-week) study duration is feasible with a fully implantable total heart, a device capacity designed for human use will lead to flow-limited pathology in growing calves. Shorter study duration is advisable for replacement heart device evaluation in the bovine model.

Because of the clinical success of left ventricular assist devices (LVADs) used for short-term "bridge to transplant" and the limited availability of donor organs, heart assist devices are being considered for long-term implantation as an alternative to heart transplantation. In an effort to improve biocompatibility, our laboratory has developed a nonthrombogenic cellular lining from genetically engineered smooth muscle cells (GE-SMC) for the Thermocardiosystems Heartmate LVAD. Smooth muscle cells have been transduced with the gene for endothelial nitric oxide synthase (NOS III) and produce NO at concentrations that reduce platelet deposition and smooth muscle cell proliferation when tested in vitro. In this investigation, the adhesive capabilities of GE-SMC linings were examined. An in vitro circulatory loop was designed to expose cell lined LVADs to in vivo operating conditions. Cumulative cell loss from cell lined LVADs was less than 10% after 24 hours of flow. Using a protocol for "preconditioning" the cell lining within the mock circulatory loop, the first implantation of an LVAD containing a genetically engineered SMC lining was successfully implemented in a bovine model. Results from this 24 hour study indicate that the flow-conditioned cellular lining remained intact with no evidence of thromboembolization and only minimal changes in coagulation studies.

BACKGROUND:Because traumatic aortic transection is associated with high mortality rates, great debate exists about the appropriate operative technique for treatment of patients who have acute traumatic aortic transection. METHODS:To determine the safety and efficacy of the "clamp-sew" method, we retrospectively reviewed our 8-year experience treating 75 patients who had aortic injuries secondary to blunt trauma. Seventy-one of these patients were treated surgically. The clamp-sew method was used in all of these operations. RESULTS:Aortic cross-clamp time averaged 24 minutes (range, 14 to 36 minutes), with 4/71 having times in excess of 30 minutes. One patient (clamp time, 28 minutes) became paraplegic. Significant associated injuries were seen in 51/75 patients (48/71 patients with operation), including intrathoracic (35 patients), orthopedic (28 patients), intraabdominal (24 patients), and central nervous system (17 patients) damage. No patient died within 24 hours of operation. Overall 30-day mortality was 12% (9/75), with 7/9 having two or more aforementioned associated injuries. Of these 7, 5 had central nervous system injuries. Two of 9 died within 30 days without two or more associated injuries: 1 Jehovah's Witness of low hemoglobin, and 1 patient of sepsis. CONCLUSIONS:Although any of several maneuvers may be appropriate in managing traumatic aortic injuries, the simple "clamp-sew" technique is a safe and effective method for the treatment of traumatic aortic transections.

Development of the Jarvik 2000 intraventricular assist system for long-term support is ongoing. The system integrates the Jarvik 2000 axial flow blood pump with a microprocessor based automatic motor controller to provide response to physiologic demands. Nine devices have been evaluated in vivo (six completed, three ongoing) with durations in excess of 26 weeks. Instrumented experiments include implanted transit-time ultrasonic flow probes and dual micromanometer LV/AoP catheters. Treadmill exercise and heart pacing studies are performed to evaluate control system response to increased heart rates. Pharmacologically induced cardiac dysfunction studies are performed in awake and anesthetized calves to demonstrate control response to simulated heart failure conditions. No deleterious effects or events were encountered during any physiologic studies. No hematologic, renal, hepatic, or pulmonary complications have been encountered in any study. Plasma free hemoglobin levels of 7.0 +/- 5.1 mg/dl demonstrate no device related hemolysis throughout the duration of all studies. Pathologic analysis at explant showed no evidence of thromboembolic events. All pump surfaces were free of thrombus except for a minimal ring of fibrin, (approximately 1 mm) on the inflow bearing. Future developments for permanent implantation will include implanted physiologic control systems, implanted batteries, and transcutaneous energy and data transmission systems.

Background. This study describes the present state of progress in the development of the Jarvik 2000 ventricular assist system.Methods. Designed for implantation in the human thorax, the system consists of a small (25 cm(3), 90 g) intraventricular axial-flow blood pump that transmits power and data via internal electronics and a transcutaneous energy transfer system. The pump is powered by portable internal and external polymer lithium ion batteries. The only moving part, the pump rotor, contains a permanent magnet of a brushless direct-current motor that mounts an axial-how impeller and partial magnetic thrust support, with blood-immersed radial and thrust bearings. The motor uses a redundant coil and electric lead design, which permits continued operation in case of wire breakage.Results. Seven calves have been supported for an average of 107 days (range, 40 to 162 days) with prototypes of the Jarvik 2000 ventricular assist system. No physiologic complications have occurred. When its user is at rest, the pump produces flows of 5 to 6 L/min with a decreased arterial pulse contour. Renal and hepatic functions have remained normal throughout the duration of all studies. Mean plasma free hemoglobin levels ranged from 4.3 to 11.4 mg/dL (mean, 6.3 mg/dL) for each study. Pathologic analyses of the heart and kidneys revealed no damage related to the device.Conclusions. These studies indicate that the Jarvik 2000 ventricular assist system is feasible in animals and holds promise for long-term support of patients. (C) 1997 by The Society of Thoracic Surgeons.

A brief history of cardiac transplants and mechanical assist devices historical developments in immunosuppressive regimens evaluation and treatment of end-stage heart disease for heart transplantation molecular biological alterations in heart failure donor selection and management the nurse's role in transplant care immunology pathology circulatory support devices surgical techniques patient management noninvasive techniques for detection of heart allograft rejection infectious diseases coronary artery disease in transplant patients paediatric patients the new immunosuppressants xenogenic heart transplantation the future.

Background. This study assessed the effect of prolonged left ventricular unloading on native ventricular function. Methods. We reviewed data from 31 patients (30 men, 1 woman) supported more than 30 days (mean, 137 days; range, 31 to 505 days) with the HeartMate left ventricular assist system. The patients' mean age was 46 years (range, 22 to 64 years); 17 had idiopathic and 14 had ischemic cardiomyopathy. Data (anatomic, physiologic, hemodynamic, histologic, and biochemical) were collected at the time of HeartMate implantation, during support with the device temporarily oh, and at the time of device explantation. Results. Routine chest roentgenogram showed improvement in cardiothoracic ratio (0.62 +/- 0.04 to 0.55 +/- 0.03; p < 0.0001). Echocardiography performed with the pump off showed a significant decrease in left ventricular end-diastolic dimension (6.81 +/- 0.87 cm to 5.39 +/- 1.08 cm; p < 0.0005) and a significant improvement in ejection fraction (0.11 +/- 0.05 to 0.22 +/- 0.17; p < 0.02). Cardiac index increased (1.96 +/- 0.52 L . min(-1). m(-2) to 2.93 +/- 0.73 L . min(-1) m(-2); p < 0.0001), mean aortic pressure increased (71.40 +/- 10.63 mm Hg to 76.33 +/- 16.84 mm Hg; p = 0.48), pulmonary capillary wedge pressure decreased (24.18 +/- 6.27 mm Hg to 14.48 +/- 3.01 mm Hg; p < 0.0001), and pulmonary vascular resistance decreased (3.34 +/- 2.00 Wood units to 2.51 +/- 0.88 Wood units; p < 0.05). Comparisons of tissue samples taken at the time of implantation and at the time of transplantation showed a marked reduction in myocytolysis. Calcium uptake, calcium-binding rates, and lipid levels normalized in patients studied. Plasma norepinephrine levels decreased to near normal levels. Conclusion. Prospective studies are now indicated to determine whether device removal without transplantation may be beneficial in selected patients.

Pennington, MD, at the time of presentation, or to the Editor of The Annals of Thoracic Surgery prior to presentation.Speakers for the Regular Program are limited to 15 minutes; those in the Forum are limited to 10 minutes.These times include the discussion.Speakers

Infection is a problem in patients undergoing support with left ventricular assist systems. To better understand the nature of this problem, we retrospectively analyzed data on 56 patients supported by the HeartMate (Thermo Cardiosystems, Inc, Woburn, MA) left ventricular assist system. Infection was defined as fever > 38 degrees C, white blood count > 12,000 cells/ml, and a need for antimicrobial therapy. Of the 56 patients, 25 (41%) had an infection. Device related infections (as determined by positive culture from driveline, housing, or inflow or outflow tract) occurred in eight patients (14.3%). The most common sites of infection were the respiratory system (42.4%), the central venous catheter (27.8%), and blood (18.3%). Of the positive cultures, 84% were bacterial and 16% fungal. There were no positive viral cultures. Positive cultures from left ventricular assist system related sites made up only 8.7% of the total. All but one of the patients with device related infections survived to transplantation. The long-term survival rate for patients in this group after transplantation was 77.8%. Two patients required surgical revision of the driveline because of infection. Both were free of infection postoperatively. Patients who stayed in the intensive care unit for longer periods had a greater risk of infection (uninfected, 35 days; infected, 78 days). In conclusion, although infection is a problem in patients undergoing support with left ventricular assist systems, it does not preclude survival to transplantation or alter the survival rate after transplantation.

Sodium nitroprusside, a potent vasodilator, was evaluated for its effect on platelet aggregation in stenosed and endothelium-injured coronary arteries in a canine model. Twenty-five anesthetized dogs were studied; coronary blood flow velocity was continuously monitored. Recurrent intracoronary platelet aggregation and dislodgment (indicated by cyclic variations in coronary blood flow) were induced by mechanically injuring and stenosing the left anterior descending coronary artery. Sodium nitroprusside was administered either intrapericardially or intravenously 30 min after cyclic flow variations were established. Intrapericardial administration of saline (control) did not affect cyclic flow variations in any of 6 tested dogs. Sodium nitroprusside abolished cyclic flow variations in all 7 dogs (100%) when given intrapericardially and in 5 to 7 dogs (71%) when given intravenously (compared to intrapericardial salines, p < 0.01). A smaller dose of sodium nitroprusside was required to abolish cyclic flow variations when given intrapericardially than when given intravenously (1.6 +/- 0.5 micrograms.kg-1.min-1 vs 4.8 +/- 0.8 micrograms.kg-1.min-1, p < 0.01). The mean aortic pressure was reduced by 10 to 20 mmHg after intrapericardial sodium nitroprusside administration and by 30 to 40 mmHg after intravenous sodium nitroprusside administration. To investigate the mechanism of protection by sodium nitroprusside, NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthetase, was used to induce cyclic flow variations in mildly injured and stenosed left anterior descending coronary arteries in 5 dogs. Intrapericardial sodium nitroprusside abolished the cyclic flow variations in all 5 dogs. Then oxyhemoglobin, an inhibitor of nitric oxide, was administered into the left anterior descending coronary arteries of these dogs, and it restored the sodium nitroprusside-abolished cyclic flow variations in all 5 dogs. Thus, sodium nitroprusside protects against platelet aggregation and cyclic flow variations in stenosed and endothelium-injured canine coronary arteries, probably by the action of nitric oxide, and it is more effective and hemodynamically safer when administered intrapericardially than when administered intravenously.

Nishimura, M.; Radovancevic, B.; Odegaard, P.; Myers, T.; Springer, W.; Macris, M. P.; Frazier, O. H. Author Information

Wasler, A.; Radovancevic, B.; Springer, W.; Myers, T.; Macris, M. P.; Frazier, O. H. Author Information

This study assessed the effect of prolonged left ventricular unloading on native ventricular function.We reviewed data from 31 patients (30 men, 1 woman) supported more than 30 days (mean, 137 days; range, 31 to 505 days) with the HeartMate left ventricular assist system. The patients' mean age was 46 years (range, 22 to 64 years); 17 had idiopathic and 14 had ischemic cardiomyopathy. Data (anatomic, physiologic, hemodynamic, histologic, and biochemical) were collected at the time of HeartMate implantation, during support with the device temporarily off, and at the time of device explantation.Routine chest roentgenogram showed improvement in cardiothoracic ratio (0.62 +/- 0.04 to 0.55 +/- 0.03; p < 0.0001). Echocardiography performed with the pump off showed a significant decrease in left ventricular end-diastolic dimension (6.81 +/- 0.87 cm to 5.39 +/- 1.08 cm; p < 0.0005) and a significant improvement in ejection fraction (0.11 +/- 0.05 to 0.22 +/- 0.17; p < 0.02). Cardiac index increased (1.96 +/- 0.52 L.min-1.m-2 to 2.93 +/- 0.73 L.min-1.m-2; p < 0.0001), mean aortic pressure increased (71.40 +/- 10.63 mm Hg to 76.33 +/- 16.84 mm Hg; p = 0.48), pulmonary capillary wedge pressure decreased (24.18 +/- 6.27 mm Hg to 14.48 +/- 3.01 mm Hg; p < 0.0001), and pulmonary vascular resistance decreased (3.34 +/- 2.00 Wood units to 2.51 +/- 0.88 Wood units; p < 0.05). Comparisons of tissue samples taken at the time of implantation and at the time of transplantation showed a marked reduction in myocytolysis. Calcium uptake, calcium-binding rates, and lipid levels normalized in patients studied. Plasma norepinephrine levels decreased to near normal levels.Prospective studies are now indicated to determine whether device removal without transplantation may be beneficial in selected patients.

Achieving local hemostasis following coronary interventions especially in patients with massive anticoagulant therapy still remains a problem in clinical cardiology. The objective of this study was to investigate the safety and efficacyof a new biosealant (modified fibrin glue) and hemostatic device (Global Therapeutics, Inc. I to reduce arterial compression time required to achieve hemostasis at the arterial puncture site. 25 New Zealand rabbits (3–5 kg) and 10 mongrel dogs (25–40 kg) were used in this study. 5F and 8F introducers were placed in the femoral arteries in rabbits and dogs respectively. After complete heparinization the hemostatic device was introduced into the puncture site through a guide wire and biosealant was applied to the outside of the vessel. Immediately after removing hemostatic device a light pressure was applied at the puncture site. Hemostasis was achieved in all animals. Mean time for hemostasis was 1.2 ± 0.8 min and 5.6 ± 4.1 min in rabbits and dogs respectively. Histopathology performed 1 month later of the puncture site in dogs revealed complete reabsorbtion of biosealant with re-endothelialization and no evidence of inflammation or hind limb thrombosis. We conclude that the hemostatic device with biosealant is a safe and effective method of hemostasis of arterial puncture sites,

The ABIOMED implantable total artificial heart is in the final phase of engineering development. The system has a compact electrohydraulically driven energy converter sandwiched between two blood pumps, an internal electronics pack, an internal battery, a transcutaneous energy transmission coil for power transmission, and external wearable electronics pack and battery. The current effort is to complete development of the system during 1996 in preparation for formal pre clinical testing of the device. In vivo studies with the current thoracic unit (ABH II) have achieved 108 days of survival verifying the thermal, physiologic, and hematologic compatibility of the system. The abdominal implantable electronics pack showed no thermal dissipation problem. System improvements include scaling down the size of the thoracic unit, and efficiency enhancement in the power and hybrid electronics. The new system (ABH III) retains the flow capacity of greater than 10 L/min. Size reduction results in an atrial to sternal dimension that would fit 98% and 75% of men and women, respectively.

An important goal of a left ventricular assist system (LVAS) is to provide long-term, safe, cost-effective mechanical circulatory support. The Heartmate LVAS (Thermo Cardiosystems, Inc., Woburn, MA), used in recent clinical trials as a bridge to transplantation, has proven extremely reliable for long periods, and its use has improved the survival rates in patients who subsequently received a donor heart. Patients who have been implanted with an LVAS often have significantly improved physical status and can leave the intensive care unit (ICU) and be treated at less expense elsewhere in the hospital. In this preliminary report, the authors analyzed hospital charges for three groups of patients: heart transplant patients who received conventional medical therapy before transplantation (Group 1), transplant patients who received in-hospital LVAS therapy (Group 2), and one patient who awaited transplantation at home while undergoing LVAS support. Group 1 patients (n = 6) received intraaortic balloon pump (IABP) support and inotropic therapy in an ICU before transplantation, Group 2 (n = 6) patients were receiving IABP support and inotropic therapy when the LVAS was implanted and eventually underwent heart transplantation. The length of hospital stay in Group 1 (51 days) was significantly shorter than in Group 2 (185 days), Mean hospital charge in Group 1 was $5,150/day; in Group 2, $3,178/day. The patient living at home incurred an average medical expense of $27/day. Although LVAS supported patients remain in the hospital much longer than do medically treated patients, their average daily in-hospital charges are much less. If the LVAS could be used as an alternative to transplantation, it might offer not only a longer, better quality life, but also a potential cost savings to patients with end-stage heart failure.

With any historical account, the perspective varies, depending on which part of the historical context the author participated in. The same can be said for the history of the development of mechanical circulatory support devices. This chapter is documented through the eyes of one of the few surgeons who has been an active participant from the beginning, based on more than 50 years of personal experience in both experimental and clinical work in Houston, Texas, at the Baylor College of Medicine and the Texas Heart Institute. There are many facets to this worldwide race, which spans more than a half century, to replace the anatomical structure itself, or at least the physiological function of this anatomical organ that defines life from death.

We are studying in vivo an intraventricular axial flow blood pump (Jarvik 2000) designed for long-term left ventricular support. The small (25 cc, 85 g) valveless pump has been placed intraventricularly in seven calves; pumps have functioned for as long as 5 months. In the four most recent long-term studies completed, calves have survived for 70, 120, 155, and 162 days (in that order); weight gain has averaged 0.56 kg/day. One study is ongoing at more than 30 days. Under resting physiologic conditions in the normal calf, the continuous flow pump produces flows of 5-6 L/min with a decreased arterial pulse contour. The device has caused no physiologic complications. Calves in the completed studies had mean free plasma hemoglobin levels of 11.4, 7.1, 6.5, and 4.3 mg/dl, respectively. We have modified the inflow structures of the device, and these results suggest that a thrombus free design with no pannus at or around the inlet of the pump can be achieved. Histopathologic analyses of the heart and kidneys in studies of as long as 5 months show no deleterious effects of this device. These studies demonstrate the feasibility of a small implanted intraventricular blood pump for long-term use. Future developments for permanent implantation will include implanted physiologic control systems, transcutaneous energy transmission systems, and implanted batteries.