MARCHIORO, TL

STARZL, TE

WADDELL, WR

English

D-Scholarship@Pitt

USE OF EXTRACORI'OREAL CADAVER PERFUSIOS FOR PREPARATION OF ORGAN HOhiOGRAFTS T. L. MARCHIORO, MD., WILLIAM R. WADDELL, M.D., F.A.C.S., AXD THOMAS E. TARZL, MD., F.A.C.S. A practical solution to the problem oE cadaver organ procurement and preservation requires provision for immediate cooling and/or perfusion of the potential homograft. I n  the present study, a simple method is described by which both these objectives are met. METHODS Thirty-two dogs were used, weighing 9 to 20 kg. The  animals were killed with an overdose of pentobarbital after arterial and venous catheters had been placed in the inferior vena cava and aorta via the femoral vessels. Respiratory failure invariably preceded disappear- ance of pulses by 5 to 15 min. During this time, 3 mg./kg. heparin was given intravenously. Four to 12 min. after cessation of the animals' circulation, extracorporeal perfusion was instituted. The  apparatus employed gravity drainage with a disposable bubble ox), 'menator, a DeBakey pump, and a heat exchanger. T h e  extracorporeal circuit was usually primed with lactated Ringer's solution, pre-cooled by recirculation to 15" C. In  2 of the experiments on liver transplanta- tion, 5y0 glucose in water was used for the priming fluid. In all experiments, 1 gm. procaine chloride per liter was added to the perfusate. Studies were first performed to determine suitable perfusion and cooling rates. After standardization of the technique, cadaver per- fusions were carried out for 1 to 14 hr. At the end of this time, either the liver or  kidney, or  both, were removed and transplanted to suit- able recipients, after recipient hepatectomy or bilateral neplirectomy had been periormed. Postoperative anti-rejection therapy was pro- vided with azathioprine. T h e  state of preservation of the homografts was judged by their function, and by subsequent histologic studies. . RESULTS Flow rates and blood pressure reqzrirements. Six dogs were studied to determine if existing data on extracorporeal perfusion in living subjects would be transferable to the cadaver. First, flow rates were adjusted to provide an arterial pressure of 70 Inm. Hg. As much as Fronr the Departments of Surge?, University of Colorado Aledical School and the Denver C'eterarrs Adrnirristration Hospital, Drnzter, Colorado. Aided by United States Public Health Service Grants A-6283, A-6344, and IZE 07735-01. 600 cc./kg./min. were required to maintain the blood pressure at this level. The  kidneys and liver became swollell and edematous in a few minutes, with transudation of large amounts of surface fluid. Ulti- mately, it was concluded that flow rates sllould be arbitrarily limited to 40 to 60 cc.!lg./min. and then reduced to 20 to 30 cc./kg./min. as the cadaver temperature dropped below 20° C. T h e  appearance of the organs was satisfactory with the use of the reduced Bow rates, although arterial pressures never exceeded 20 mm. Hg, and were usually undetectable. . Degree of cooling. Fi\.e dogs were cooled to 2" to lo0 C.  with the low flow perfusion. This invariably required less than 60 min. Trans- plantation was carried out immediately thereafter. Upon revascu- larization, the kidneys temporarily assumed a mottled appearance, with islands of qanotic tissue surrounded by normal parenchyma. IVithin an hour, these areas disappeared and the kidneys seemed normal. Nevertheless, the dogs were anuric until death. These events were not observed with temperatures of 15" C.  or above. I t  was con- cluded that cooling to less than 10° C. was harmlul, and, in the definitive series, the ultimate temperatures were controlled at  15O C. Retzal homografts. Eleven kidneys were grafted after perfusion for 1 to 14 hr. Perfusion time for 5 of the 11 cadavers was 11 or more hours. ;\lean perfusion time was '7 hr., 33 min. All animals produced urine within the first 48 hr. Postoperative survival averaged 20 days with a range of 7 to 47 days. Survival time was influenced more ad- versely by pneuinonia than by rejection. Seven dogs died of pneumonitis. Only 5 of the 11 animals were uremic at the time of death, I\lith perfusion for 6 or more hours, sharp rises in BUN were observed iminediately after operation, with subsequent return toward normal. JVith perfusions of 6 hr. or less, early azotemia was not prominent. Histologic sections of the renal grafts showed varying degrees of mononuclear infiltrate compatible with minimal rejec- tion. Xo other pattern of parenchymal injury ascribable to per- fusion was detectable. Hepatic ho?nografts. Ten  livers were transplanted after perfusion for 71 to 416 min. Consistent clotting deficiencies were detected in every animal after the homografting, wit11 increases in fibrinolysins and decreases in fibrinogen. Five of the animals died of hemorrhage on the operating table or in the immediate postoperative period. T h e  other 5 animals lived for 1 to 5 days, although autopsy revealed hemoperitoneum in 3 of these. Hepatic function was inferred from the facts that the animals awoke from nembutal anesthesia and that they survived u-ithou~ glucose therapy. Nevertheless, acute rises in SGOT and bilirubin indicated that severe hepatic injury had oc- curred. Histologic sectiolls showed varying degrees of parenchymal injury which couId not be ascribed to rejection. The changes con- sisted of centrilobular congestion and necrosis. Clinical application. Two cadaveric renal and 2 cadaveric hepatic homografts, prepared with this technique, have been used clinically. One liver graft provided satisfactory function for 22 days until death from pulmonary embolus. Histologic structure was essentially normal at autopsy. One renal graft functioned for 2 weeks and then become anuric. The other 2 organ grafts had no evidence of function. Problems of perfusion were encountered with human cadavers, which had not been seen in dogs. In  the first 3 clinical cases, poor venous return resulted in less than optimal perfusion. In the last case, in which a satisfacton liver was obtained, this was avoided by acutely expanding the blood volume immediately after death with transEusion of whole blood and plasma. SUCCESSFUL STORiGE OF KIDNEYS .4T SUB-ZERO TEIIPEZITURES PRABHAKAR J. DESHPAXDE, A.M.S., AND STANLEY I V .  JACOB, R.I.D., F.A.C.S. Previous attempts in this laboratory to preserve the function of kidneys stored in a frozen state outside the body and subsequently autotransplanted have been unsuccessful. We are currently evaluat- ing the effects of sub-zero cooling with the hope of prolonging the period of safe renal ischemia prior to transplantation. In  this tech- nique, the freezing point is depressed to between - 5 O  to -6O C. and the kidney stored at that temperature. Fifteen experiments have been carried out on dogs. In these, the right kidney was mobilized transperitoneally and prior to its removal surface cooled to 13" C. over a 15 min. period. The renal artery was tied and the pedicle injected with 1 cc. of 27, procaine and 10 mg. of From the Department of Surgery, University of Oregon Medical School, Portland, Oregon. Thh investigation was supported by Public Health Service Research Grant CA-04780-05 from the National Cancer Institutr, Plrblic Health Ser~ice. 

USE OF EXTRACORPOREAL CADAVER PERFUSION FOR PREPARATION OF ORGAN

http://d-scholarship.pitt.edu/3450/1/31735062123900.pdf

USE OF EXTRACORPOREAL CADAVER PERFUSION FOR PREPARATION OF ORGAN

Abstract

Similar works

Full text

Available Versions

D-Scholarship@Pitt