Development of an orthotopic cardiac prosthesis

May

Volume 65, Number 5

1973

THORACIC AND CARDIOVASCULAR SURGERY The Journal of

Development of an orthotopic cardiac prosthesis John H. Kennedy, Michael E. De Bakey, William W. Akers, James N. Ross, Jr., William O'Bannon, Lee E. Baker, Stanley D. Greenberg, David W. Wieting, C. Willard Lewis, Minoru Adachi, Clarence P. Alfrey, Ir., William J. Spargo, William Walker, and John M. Fuqua, Ir., Houston, Texas

Development of an artificial heart is justifiable for three reasons: First, a reliable artificial heart theoretically could provide longer life for patients in terminal cardiac failure when only the heart is damaged beyond treatment by contemporary medical and surgical means.' Second, since the function of a cardiac prosthesis can be manipulated, such a device permits control of one variable, the heart, while other physiologic factors are analyzed. Finally, an understanding of the various factors involved in total replacement of the heart can lead to improved techniques for temporary partial support of the natural heart. From Baylor College of Medicine, Houston, Texas 77025 and Rice University, Houston, Texas 77001. Research supported in part by U.S. Public Health Service Grant HL-13330 from the Cora and Webb Mading Department of Surgery, Taub Laboratories for Mechanical Circulatory Support, Baylor College of Medicine, Houston, Texas 77025, and U.S. Public Health Service Grant HL-09-025, Rice University, Houston, Texas 77001. Presented at the Annual Scientific Sessions, American Heart

Association, Dallas, Texas, Nov. 18, 1972. Received for publication Jan. 25, 1973.

The cardiac prosthesis described in this report has been developed by a thirty-one member interdisciplinary team which includes several members with over 10 years of experience in the development of the artificial heart. The group has sought an understanding of basic physiologic mechanisms rather than placing an emphasis on length of survival. The present biventricular artificial heart is a direct outgrowth of the design of a paracorporeal left heart bypass pump, which was previously reported from this laboratory." 3 A series of modifications has been made since the report in 1969 4 ; however, the basic design has remained unchanged, resembling two pneumatically powered diaphragm pumps for left heart bypass which replace, rather than operate concurrently with, the natural heart. Materials and method

The right and left ventricles (Fig. 1) are hemispherical gas-powered diaphragm pumps fabricated of methyl methacrylate

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Fig. 1. Current prototype of orthotopic cardiac prosthesis (Mark VI, 1972).

Fig. 2. Power console for observat ion of an animal following implantation of artificial heart device.

with a flexible diaphragm of Dacron-reinforced dimethyl syloxane. Each ventricle contains an inflow and outflow valve. Initial prototypes utilized heterograft aortic valves

while subsequent designs have employed a variety of leaflet, disc, and ball valves. While a circular-segment occluder valve described by LeMole- has proved satisfactory in the inlet position, prosthetic valves have proved uniformly unsatisfactory in the outflow position because of the problems of transvalvular gradients and systemic embolism. This has led to use of stented heterograft valves. The current prototype utilizes gas power for the ventricles, which is provided by a power unit via transcutaneous polyvinyl chloride tubing. As previously reported,' preliminary experiments with an orthotopic cardiac prosthesis capable of pumping 5 L. of blood per minute proved insufficient to permit long-term survival of animals weighing 100 kilograms ; the postoperative state resembled that of exercise biochemically. In addition , it became clear that since this "heart" was fabricated of synthetic polymers rather than living myocardium, above a given mean atrial pressure there was little increase in cardiac output since, unlike the natural heart, the artificial heart lacks homeometric autoregulation. Since the artificial heart was powered by gas, which was compressible,

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Fig. 3. Surgical implantation of an artificial heart in a 100 kilogram calf.

there was an unfavorable response to afterloading. When peripheral vascular resistance was decreased by half there was an increase in instantaneous flow. Conversely, when peripheral vascular resistance rose, pump output fell. The dual pneumatic power unit (Fig. 2) has two major subsystems: the pneumatic pressure sources and the monitor and control unit. The two pneumatic power units, each with a motor-driven pump, generate gas pressure and vacuum necessary for pulsing the prosthesis. Each of the pneumatic pressure sources consists of a compressor, a pressure (ejection) regulator, a vacuum (filling) regulator, a pressure gauge, a vacuum gauge, a three-way solenoid pilot valve, and a pneumatic transfer valve. In operation, the ejection pressure and the filling vacuum are connected alternately to the output line by the pneumatic transfer valve, which is controlled in the monitor and control unit. Pressures of zero to 250 mm. Hg and a vacuum of zero to 50 mm. Hg can be adjusted instantaneously by the regulator. A one-third horsepower motor powers the pump in each unit, which requires 345 Ma. at 15 volts, 60 Hz. The transmitting gas is compressed air. Pulse rate and systolic duration are controlled in the pulse unit, which also provides for synchronization of the two pneumatic sources. The monitor

Fig. 4. Animal drinking after implantation of an artificial heart.

and control unit consists of a display oscilloscope, four pressure preamplifiers, and the pulse unit . The oscilloscope was modified from a commercial unit, and the pressure amplifier and pulse unit were designed at Rice University. The latter, consisting of electronic rate and duration circuits, controls the solenoid valve which applies pressure and vacuum alternately to the prosthesis. The pulse unit incorporates a relaxation oscillator (rate), adjustable over a range of 20 to 120 pulses per minute, and two mono-stable multivibrators (right and left systolic duration), adjustable over a range of 100 to 900 msec. The two timers are

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Fig. 6. Measurements of thoracic electrical impedance-"cardiac" output obtained following implantation of our artificial heart device. Left ventricular ejection (right ventricle slot) constitutes 60 per cent, whereas the right constitutes 40 per cent. BP, Blood pressure. l1Z, Change in impedance. (Reprinted from Kennedy, J. H., and associates, Biomaterials, Medical Devices, and Artificial Organs 1: 1, 1972, by permission of Marcel Dekker, Inc., New York, N. Y.)

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Fig. 11. Appearance of the kidney following implantation of an orthotopic cardiac prosthesis. There is focal infarction due to arterial emboli.

Fig. 12. Light microscopic appearance of the lung following implantation of an artificial heart device. There is congestion and atelectasis.

identical and one power unit can be triggered synchronously with the other, an essential feature for a biventricular artificial heart. Surgical implantation has routinely been carried out through a right thoracotomy incision under Fluothane-nitrous-oxide-oxygen anesthesia via a previously placed tracheotomy, necessary because of the need

for prolonged postoperative respiratory support. The technical surgical maneuvers have been similar to those employed for cardiac allografting? and have been carried out under hemodilution cardiopulmonary bypass at normothermia with a disposable bubbledispersion oxygenator (Travenol 6Lf) primed with 5 per cent dextrose and distilled water. Duration of cardiopulmonary

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Surgery

bypass has been approximately 1 hour in most animals. Postoperative management of the animals has required a veterinary intensive care unit with careful maintenance of ventilation, acid-base balance, and blood volume. This has required three shifts of two people: one an engineer familiar with the operation of the console and the other to act as a nurse for the animal. In favorable experiments, the animals have regularly awakened hungry and thirsty (Fig. 4). One animal was successfully resuscitated after he leapt from the restraining cage, disconnecting the pneumatic lines. Results

Between Aug. 4, 1970, and Sept. 26, 1972, 29 calves have undergone implantation of one or another modifications of the Baylor-Rice orthotopic cardiac prosthesis; the average survival was 19.3 hours. Nine animals lived more than 12 hours, and the longest survival period was 124 hours. Normal neurologic function has been a concomitant of what is termed "survival." Hemodynamic observations following a typical experiment are shown in Fig. 5. Note that once stability of blood volume (and hence venous return) is achieved, the pump requires little "tuning." Total body flow was measured by impedance or by dilution techniques. These techniques, however, indicate little about the partition of flow to specific organs. The distribution of perfusion has been inferred from changes in the partition of microspheres (15 ± 5 fL) labeled with HlCe, "Sr, or 51Cr. Fig. 7 is an illustration of the marked changes in the distribution of flow as pumping by the natural heart is replaced by that of an artificial heart; there is increased perfusion to kidney at the expense of that to the brain. Changes in distribution of perfusion are reflected in biochemical findings. The arterial blood acid-base data in a typical experiment, when favorable hemodynamics have been present postoperatively, show that acid-base balance remained relatively normal (Fig. 8). Note the gradual downward trend of the value for arterial P0 2 and the

gradual increase in Pco~. The value for the serum glutamic oxaloacetic transaminase rose progressively, which in the cow indicates nonspecific tissue necrosis. As shown in Fig. 9, the serum total protein and electrolyte values remained relatively normal. In Fig. 10, which summarizes the hematologic findings, there was a progressive increase in the value for the plasma-free hemoglobin and an initial fall by 80 per cent in the platelet count, which then stabilized in a relatively innocuous range. There was a slight increase in the value for the prothrombin time; the partial thromboplastin time increased twofold. Histopathologic examination of the animals after termination of the experiments, aside from the results of surgery and postoperative hemorrhage, showed evidences of peripheral arterial emboli most marked in the kidney but also in the brain (Fig. 11). The most striking abnormalities were in the lungs (Fig. 12); congestion, atelectasis, and the picture of acute pulmonary edema were found, whether or not left atrial pressure had been elevated. Electron microscopy (Fig. 13) revealed imbibitional edema within interstitial tissue and the alveolar septa, absence of microthromboemboli, and selective degeneration of Type I alveolar epithelial cells. Discussion

The data which have been collected cannot be regarded as encyclopedic. However, as one reviews our 2 years' observation of the fate of animals following implantation of an artificial heart device, it is, of course, disheartening that previously healthy animals are rendered moribund by one or another variation of a pneumatically powered orthotopic cardiac prosthesis, an experience shared by all investigators to date (July 30, 1972). The terminal event has been uniform, resembling cardiogenic shock in which the heart, being externally powered, continued to pump. While implantable power sources have been a matter of interest to several research groups (more recently nuclear energy? has been applied for

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Fig. 13. Electron micrograph of calf lung shows septal edema (e) and destruction of Type I pneumocytes (arrows).

this purpose), it is our belief that there are other restraints of a greater order of magnitude which at the present time are impeding progress in this interesting area of endeavor. These are the development of the following: durable, flexible, biocompatible materials; a system which is responsive to

existing neurohumeral cardiovascular control; and a pump which provides the organism with a pressure wave form as similar to that of the heart as possible. Otherwise, the pump is regarded as an intrusion or a perturbation in a carefully ordered cybernetic system. Until these problems are resolved,

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whether the power source is transcutaneous or totally implanted Becomes somewhat less important. In our own experience, calves have been able to accept transcutaneous pneumatic power lines for as long as 124 hours. Summary

1. The results of an experience with 29 calves over a 21 month period, during which I calf survived 124 hours after implantation of a gas-powered, biventricular, total orthotopic cardiac prosthesis, have been described. 2. The abnormalities noted in the postoperative period included thrombosis in the prosthesis with multiple arterial emboli, redistribution of the available flow to the kidney at the expense of the brain, and the histologic picture of post-traumatic pulmonary insufficiency. 3. The current restraints to further progress in this field have been reviewed. REFERENCES

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Report TE15-66 (R), Task I, Assessment and Definition of the Problem: A Report from the Children's Hospital Medical Center, Boston, and Thermo Electron Engineering Corp., Waltham, Mass., 111-26, December, 1965. De Bakey, M. E.: Left Ventricular Bypass Pump for Cardiac Assistance: Clinical Experience, Am. J. CardioI. 27: 3, 1971. Akers, W. W., O'Bannon, W., Hall, C. W., et aI.: Design and Operation of Paracorporeal Bypass Pump, Trans. Amer. Soc. Artif. Intern. Organs 12: 86, 1966. Kennedy, J. H., De Bakey, M. E., Akers, W. W., Ross, J. N., Jr., Walker, W. A, O'Bannon, W., Baker, L. E., Greenberg, S. D., Wieting, D. W., Lewis, C. W., Adachi, M., Alfrey, C. P., Jr., Spargo, J. J., and Fuqua, J. M., Jr.: Progress Toward an Orthotopic Cardiac Prosthesis, Biomater. Med. Devices Artif. Organs 1: 1, 1972. LeMole, G. M., Wieting, D. W., and Cooley, D. A: In Vitro and In Vivo Flow Patterns of Mitral Valve Prostheses: Development of an Elliptical Valve, Trans. Am. Soc. Artif. Intern. Organs 15: 200, 1969. Stinson, E. B., Dong, E., Jr., Biber, C. P., Schroeder, J. S., and Shumway, N. E.: Cardiac Transplantation in Man: I. Early Rejection, 1. A. M. A. 207: 2233, 1969. Akutsu, T., and Kolff, W. J.: Permanent Sub-

stitutes for Valves and Hearts, Trans. Am. Soc. Artif. Intern. Organs 4: 230, 1958. 8 Kolff, W. J.: An Intrathoracic Pump to Replace the Human Heart: Current Developments at the Cleveland Clinic, Cleve. Clin. Q. 29: 107, 1962. 9 De Bakey, M. E., and Hall. C. W.: Towards the Artificial Heart, New Sci., 8: 51, 1964. IO Kusserow, B. K.: Artificial Heart ResearchSurvey and Prospectus, Trans. N. Y. Acad. Sci. 27: 309, 1965. 11 Nose, Y., Topaz, S., SenGupta, A, Tretbar, L. L., and Kolff, W. J.: Artificial Hearts Inside the Pericardial Sac in Calves, Trans. Am. Soc. Artif. Intern. Organs 11:255, 1965. 12 Kelly, E.: Intracorporeal Mechanical Heart, Interscience Research Institute Report, DHEW, NIH Grant No. HE 05641-05, 1966. 13 De Bakey, M. E., Liotta, D., and Hall, C. W.: Prospects and Implications of the Artificial Heart and Assistive Devices, J. RehabiI. 32: 106, 1966. 14 Wildevuur, C. R. H., Mrava, G. L., Crosby, M. J., Wright, J. I., Hladky, H. L., Anderson, G. J., Pierson, R. M., Kon, T., and Nose, Y.: An Artificial Heart Sensitive to Atrial Volume, Trans. Am. Soc. Artif. Intern. Organs 14: 276, 1968. 15 Petrovsky, B. V., and Shumakov, V. I.: Problems of Artificial Hearts and Their Experimental Study, J. THORAc. CARDIOVASC. SURG. 57: 431, 1969. 16 Sarin, C. L.: Haemodynamic Studies in Calves Sustained on Artificial Hearts, Ann. R. Call. Surg. EngI. 45: 23, 1969. 17 Akutsu, T., Takagi, H., Takano, H., and Farish, C.: Total Heart Replacement Device and its Control and Driving System, Proc. Artif. Heart Progr. Conf., Washington, D. c., 581, 1969. 18 Nakamura, R., and Redo, S. F.: Experience With a Polyurethane Sac-Type Artificial Heart, Trans. Am. Soc. Artif. Intern. Organs 15: 237, 1969. 19 De Bakey, M. E., Hall, C. W., Hellums, J. D., O'Bannon, W., Bourland, H., Feldman, L., Wieting, D., Calvin, S., Smith, P., and Anderson, S.: Orthotopic Cardiac Prosthesis: Preliminary Experiments in Animals With Biventricular Heart, Cardiovasc. Res. Cent. Bull. 7: 127, 1969. 20 Kwan-Gett, C., Zwart, H. H. J., Kralios, A. c., Kessler, T., Backman, K., and Kolff, W. J.: A Prosthetic Heart With Hemispherical Ventricles Designed for Low Hemolytic Action, Trans. Am. Soc. Artif. Intern. Organs 16: 409, 1970. 21 Kwan-Gett, C., and Kolff, W. J.: Personal communication, November, 1970. 22 Klain, M., Ogawa, H., Wright, J., Webb, J.,

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Mrava, G., Von Bailey, K., Urbanek, K., Carse, c., Sagawa, K" and Nose, Y.: Valveless Orthotopic Cardiac Prosthesis: A Wave-Pulsating Total Heart, Trans. Am. Soc. Artif, Intern. Organs Hi: 400, 1970. Akutsu, T., Takagi, H., and Takano, H.: Total Artificial Hearts With Built-in Valves, Trans. Am. Soc. Artif. Intern. Organs 16: 392, 1970. LeBlanc, J.: Plastic Hearts-Made in Mississippi, Dixie, 29, June, 1971, pp. 11-16. Klain, M., Mrava, G. L., Tajima, K., Schriber, K., Webb, J., Ogawa, H., Opplt, J., and Nose, Y.: Can We Achieve Over 100 Hours' Survival With a Total Mechanical Heart? Trans. Am. Soc. Artif. Intern. Organs 17: 437, 1971. Takano, H., Takagi, H., Turner, M. D., Henson, E. C., Crowell, J. W., and Akutsu, T.: Problems in Total Artificial Heart, Trans. Am. Soc. Artif. Intern. Organs 17: 449, 1971. Lyman, D. C, Kwan-Gett, C., Zwart, H. H. J., Bland, A., Eastwood, N., Kawai, J., and Kolff, W. J.: The Development and Implanta-

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tion of a Polyurethane Hemispherical Artificial Heart, Trans. Soc. Artif. Intern. Organs 17: 456, 1971. Kwan-Gett, C., Backman, D. K., Donovan, F. M., Eastwood, N., Foote, J. L., Kawai, I., Kessler, T. R., Kralios, A. c., Peters, I. L., Van Kampen, K. R., Wong, H. K., Zwart, H. H. J., and Kolff, W. I.: Artificial Heart With Hemispherical Ventricles II and Disseminated Intravascular Coagulation, Trans. Am. Soc. Artif. Intern. Organs 17: 474, 1971. Harmison, L. T.: Totally Implantable Artificial Heart, National Heart and Lung Institute Report, February, 1972. Kawai, J., Peters, 1. L., Donovan, F. M., Ir., Zwart, H. H. J., Hershgold, E. I., and Kolff, W. J.: Successful Use of Deep Hypothermia for Implantation of the Artificial Heart in Calves, Circulation 44: 184, 1971 (Suppl. 11). Lance, I. R., and Selz, A.: An Implantable Artificial Heart Power Source, Isotop. Rad. Technol. 7: 182, 1969.