TIOMOTRANSPLANTATION OF THE AORTIC VALVE ARTHUR C. BEALL, Jr, M.D. GEORGE C. MORRIS, Jr., M.D. DENTON A, COOLEY, M.D. and MICHAEL E. DE BAKEY, M.D. TIouston, Texas From the Cora and Webb Mading Department of Surgery, Baylor University College of Medicine Reprinted from THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY St. Louis Vol. 42, No. 4, Pages 497-506, October, 1961 (Copyright @ 1961 by The C. V. Mosby Company ) (Printed in the U. S. A.) HOMOTRANSPLANTATION OF THE AORTIC VALVE Arthur C. Beall, Jr., M.D., George C. Morris, ]r., M.D., Denton A. Cooley, M.D., and Michael E, De Bakey, M.D., Houston, Texas ARDIAC valve homotransplantation came as a logical evolvement of the suc- C cessful use of vessel homografts. Cusp homografts have been used in both the tricuspid and the aortic valves. From such studies have come conflicting reports.”® °° °° Many attempts to homotransplant the entire aortie valve have met with failure duc to hemorrhage® *° or to degeneration of the cusps over a period of time.* * ?° ?> However, in only one of these studies was a need for the valve created, and here the aortic insufficiency produced was only temporary in the majority of the animals.2* Such an experiment cannot be considered conclusive.?4 Hemorrhage from aortic valve homografts ean be prevented by various technical maneuvers.?> Murray has shown experimentally that aortie valve homo- grafts will continue to function in the presence of permanent aortic insuffi- ciency,*4 and has utilized such valves successfully in several human pa- tients.** ** 34 As yet no one has attempted to confirm these findings. The fate of valve homografts is not clear. In such a valve are many inherent advantages. Although vessel grafts of various synthetic materials are now being used with inereasing frequeney in arterial reconstruction, no entirely satisfactory synthetic valve is available. In an effort to elarify the usefulness of aortic valve homografts in a hemodynamic environment which requires the presence of a valve, the following study was undertaken. METHOD Mongrel donor dogs, similar in weight to recipient animals, were sacrificed, and the hearts removed under sterile conditions. The aortic valve was exeiscd in such a manner as to include 1.0 em. of ascending aorta and a small amount of proximal myocardium. A 1.0 to 1.5 em. segment from the ascending aorta was meticulously sutured as a cuff to the myocardial side of the valve with simple, running 5-0 arterial silk. The coronary orifices were oversewn with 5-0 arterial silk. The valve was then refrigerated from 2 to 48 hours in an antibiotic containing electrolyte solution similar to that described by Grogs.18 From the Cora and Webb Mading Department of Surgery, Baylor University College of Medicine, Houston, Texas, Supported in part by grants from the Houston Heart Association and the U. 8S. Public Health Service (H-3137) and under a research fellowship grant from the Houston Heart Asso- ciation. Received for publication Sept. 6, 1960. 497 498 BEALL ET AQ, J. Thoracic and Cardiovas. Surg. Mongrel recipient dogs, varying in weight from 11.3 to 29.5 kilograms, were anes- thetized with Nembutal sodium, 30 mg. per kilogram. Intermittent positive pressure oxygen was administered through an endotracheal tube. In the lateral position the chest was entered through the fourth left intercostal space, utilizing aseptic technique. A 4 to 5 em. segment of the proximal descending thoracic aorta was freed, ligating one or two pairs of intercostal arteries. The aorta was occluded proximally and distally with arterial clamps, and a segment of the same length as that of the valve to be inserted was excised. A. previously prepared aortic valve homograft was then sutured in place using simple, running 5-0 arterial silk (Fig. 1). Neither hypothermia37 nor pump bypass31 was used, as the period of aortic occlusion was only 20 to 25 minutes and no difficulty was noted from aortic ocelusion of this duration. After the valve was in place, clamps were slowly released, and stored blood was given as indicated. For a brief period there was often some bleeding from the mycardial suture line, but this readily stopped if the clamps were re- leased slowly. Only one operative death could be attributed to hemorrhage, and this was the first animal in which the procedure was carried out. Fig. 1.—Aortie valve homograft sutured into descending thoracic aorta. After allowing sufficient time for the animals to stabilize from this procedure, generally 10 to 15 minutes, aortic insufficiency was created by a technique previously reported.11 The left subclavian artery was divided 2 to 3 em. from the aortic arch, and the distal cut end ligated. Under control of a tourniquet, a bent crochet hook was introduced into the aortic areh through the proximal cut end of the subclavian artery. This was passed into the sinus of the posterior cusp of the animal’s own aortic valve, guided by a finger along the outer posterior wall of the intrapericardial aorta. The hook was punched through the cusp, and the cusp grasped and avulsed. The hook was removed, and the subclavian artery ligated. The chest was closed, drainage catheters were removed, and the animals returned to their cages. Penicillin and streptomyein were given for 5 days. At intervals of 1, 3, 6, 9, and 12 months after operation, arterial pressure tracings were taken simultaneously proximal (right brachial artery) and distal (femoral artery) to the homograft valves, utilizing Statham strain gauge manometers and an Electronics for Medicine recorder. At the time of sacrifice, the animals’ own aortic valve was examined for the presence of insuffi- ciency. The homograft valves were tested for competence to water pressure, the leaflets examined, and slides made for microscopic study. Vol. 42, No. 4 HOMOTRANSPLANTATION OF AORTIC VALVE 499 October, 1961 . 240 260 - 240 ~ Dow O-87 240 - 220, + . 220 Dog J-85 200 « 2000 180 - 180 ,i6o - 160 140 ~ 140 120 + 120 ipo « 100 80 - 80 60 60 - 40 40 . SO 20 « 0 - 0 mM 6 A mm, B Hg He. 200 « i : 240 - 220 - ~ : 200 - Dog M-46 Dog I-36 A nit, ( rut Hee Hee Fig. 2A, Simultaneous arterial pressure tracings proximal and distal to aortic valve homograft 3 months after operation. B, Simultaneous arterial pressure tracings proximal and distal to aortic valve homograft 13 months after operation. C, Simultaneous arterial pressure tracings proximal and distal to aortic valve homograft 6 months after operation. D, Simultaneous arterial pressure tracings proximal and distal to aortic valve homograft 13 months after operation. 500 BEALL ET AL. J. Thoracic and Cardiovas. Surg. RESULTS Twenty-five animals underwent this combined procedure with only four operative deaths. As previously mentioned, the first was due to hemorrhage. Another was associated with progressive heart failure following valvotomy. The other deaths were secondary to irreversible ventricular fibrillation, which occurred at the time of valvotomy. Five animals died during the first month after opera- tion: 2 from heart failure, 2 from pulmonary complications, and 1 from empyema. Fig. 3. Fig. 4. Fig. 3.—Aortic valve homograft 3 months after operation. Competence to water pressure proved at time of sacrifice. Fig. 4.—Aortic valve homograft 13 months after operation. Cusps have become some- what thickened but remain pliable and competent to water pressure. Sixteen animals were available for study 1 to 18 months after operation. Five of these died from various causes during the second and third months after surgery, and 1 was killed in a fight. Seven were sacrificed at intervals up to 18 months, and 3 are still alive and well, 3, 8, and 18 months after the insertion of a homograft valve and the creation of aortic insufficiency. In 3 animals still being followed, simultaneous pressure tracings reveal typical curves of aortic insufficiency proximal to the homograft valves with normal curves distally (Fig. 2, A and B). Similar pressure tracings were seen in 9 of the other 18 animals (Fig. 2, C and D), and competence of these homo- graft valves was confirmed by water pressure at the time of death or sacrifice. Examination of the cusps revealed slight thickening, but they remained pliable, and quite capable of function (Figs. 3 and 4). Microscopically valvitis with polymorphonuelear and lymphocytic infiltration was seen during the first month Vol. 42, No. 4 HOMOTRANSPLANTATION OF AORTIC VALVE 501 October, 1961 Fig. 5. Fig. 6. Fig. 5.—Photomicrograph of homograft cusp 1 month after operation. Minimal inflam- matory response is present. Fig. 6.—Photomicrograph of homograft cusp 13 months after operation. Cusp acellular and hyalinized with ground-glass appearance, but valve remains competent. 502 BEALL ET Al. J. Thoracic and Cardiovas. Surg. 4 - BOG J-30 4 200 180 160 140 120 160 1 : 80 - eo 40 20 o 4 Ame | He, i Fig. 7.—-Simultaneous arterial pressure tracings proximal and distal to aortic valve homograft. Proximal and distal tracings similar throughout period of study. Fig. 8.— Aortic valve homograft 11 months after operation. Valve not competent to water pressure, but appears distorted at myocardial suture line. Vol. $2, No, # HOMOTRANSPLANTATION OF AORTIC VALVE 503 after insertion, but was seen only rarely thereafter. Over a period of months, the cusps developed an acellular, hyalinized, ground-glass appearance (Figs. 5 and 6). Competence could not be proved in the 4 remaining animals; in 2, pres- sure tracings proximal and distal to the homograft valves were similar throughout the period of study (Fig. 7). At the time of sacrifice, the homograft valves were not competent to water pressure, but the cusps were in good condition and capable of funetion (Fig. 8). One cannot help but speculate that these valves were distorted when the disproportionate myocardial anastomosis was made and were never competent. In the other 2 animals, marked sclerosis with shrinking of the cusps was noted at the time of death at 314 months in 1, and at the time of sacrifice at 11 months in the other. Pressure tracings in these 2 animals revealed progressive loss of insufficiency proximal to the homograft valves, and examination of their own aortic valves suggested that the torn posterior cusp had been compensated for by the right and left coronary cusps as previously noted by Lam.2* It would appear that loss of function in these two homograft valves was associated with the spontaneous disappearance of aortic insufficiency in the animals’ own aortic valves. DISCUSSION Many ingenious techniques have been developed for the treatment of valvar lesions of the heart. Autogenous tissue has been used experimentally for both the atrioventricular and aortie valves.t> * & 11:16 1% 30 35, 38, 4% 44 45 The entire pulmonic valve has been transplanted into the descending thoracic aorta.*s In recent years numerous foreign materials have been used both experimentally and elinieally in eardiac valve surgery.” 4, 5, 8, 9, 10, 12-15, 19-23, 27, 29, 40, 41, 43, 46, 47 = AT. though many of these valve substitutes have shown considerable promise, none has been entirely satisfactory. The ideal location for an aortic valve replacement would be proximal to the coronary orifices. The desecnding thoracic aorta was chosen for the present investigation, as this location allowed pressure tracings to be taken proximal and distal to the valves without re-opening the chest. Clinically many gratifying results have been obtained from the placement of plastic ball valves in the descending thoracic aorta.2* 41 Until a satisfactory subeoronary valve replace- ment is available, it would seem advisable to continue to use the descending thoracic aorta without interfering with the function remaining in the patient’s own aortic valve. This does not allow exeision and replacement of a stenotic and destroyed valve, but docs offer palliation to patients with aortic insufficiency until such time as the valve can be replaced in its entirety. As with vessel homografts, valve homografts, if suecessful, will eventually be replaeed by a more satisfactory material. Even now, the final answer in vessel grafts has not been found. No human data are ineluded in this series, but Murray has reported clinical success with aortic valve homografts in patients with aortie insufficiency for periods up to more than 4 years.*? °° This type of procedure is contemplated in the near future, and should alleviate some of the us — Cindiovas. Sore problems seen with plastic ball valves, such as noise, destruction of formed elements of the blood, emboli, and complications resulting from the insertion of a rigid tube into the pulsatile aorta. Attempts are now being made to transplant aortic valve homografts into a subeoronary position in the dog. With technical advances made in recent years, present techniques of total cardiopulmonary bypass allow adequate exposure of the aortic valve area. Total excision and subcoronary replacement of the aortic valve awaits only the development of a satisfactory valve and a method of adequately securing it in place. SUMMARY Previous attempts to homotransplant aortic valves have generally met with failure, due to hemorrhage or to loss of eusp function in experiments in which no aortic insufficiency was created or the insufficiency produced spontaneously disappeared. Kneouraged by occasional reports of successful cardiae valve homografts, a study was carried out in which an aortic valve homograft was inserted into the descending thoracic aorta of the dog. Aortic insufficiency was then created, and the animals were followed at intervals by pressure tracings taken proximal and distal to the homograft valves. At the time of death or sacrifice the valves were tested for competence to water pressure and examined grossly and microscopically. Sixteen animals were studied from 1 to 18 months after operation. In 12 the homograft valves remained functional. In 2 the valves did not appear com- petent throughout the period of study, but the eusps remained in good condition and appeared eapable of function. In 2 animals in which aortic insufficiency spontaneously disappeared, the homograft cusps underwent degenerative changes, and the valves became functionless. 1t would appear from these findings that homotransplantation of the aortic valve is technically feasible, and that such a valve will continue to function if a need for the valve exists. ADDENDUM Feb. 18, 1961. Since this experimental study was submitted for publication, aortic valve homografts have been sutured into the proximal descending thoracic aorta of 3 patients with severe aortic regurgitation. Pump bypass from the left atrium to the femoral artery was utilized during the period of sortie occlusion. These patients have shown definite clinical improvement with decrease in heart size, 7, 6, and 5 months after operation. There has heen no evidence of regurgitation in any of these homograft valves. REFERENCES 1. Absolon, K. B., Hunter, 8. W., and Quattlebaum, F. 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