[109 orthotopic hepatic transplantations. Evaluation of our experience].
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Biomedical subjects
Publications and source records attributed to D Houssin.
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Natural antidonor antibodies are known to play a prominent role in hyperacute xenograft rejection. The aim of this work was to devise an experimental protocol to prolong the survival time of guinea pig heart xenografts transplanted into rats. A technique of continuous plasma exchange adapted to small animals was used to remove the natural cytotoxic antibodies from the recipient prior to the transplantation. In some experiments, cyclosporine (CsA), cyclophosphamide (CY), or splenectomy were associated with the plasma exchange. In this highly discordant xenogenic donor-recipient combination, the mean graft survival time in nontreated rats was 16 min. When an exchange of 1.5 plasma volume was performed 24 hr before the transplantation, no prolongation of the graft survival time was observed. When CsA, CY, or splenectomy were associated with the plasma exchange, the graft survival time was significantly increased by more than 2500% (up to 418 min with CsA). When used isolately, none of these 3 immunosuppressive methods was able to prolong the graft survival time. Natural cytotoxic antibodies were monitored by a complement-mediated cytotoxicity assay. After a plasma exchange, the titers decreased from 1:16-1:32 to 1:1-1:2. When no immunosuppressive method was associated with the plasma exchange, the antibodies returned to their initial level within the 24 hr that preceded the transplantation, and the graft was rejected as in nontreated animals. When an immunosuppressive method was associated with the plasma exchange, and particularly in the case of CsA, the titers remained low, and the hyperacute rejection was delayed. Therefore, it can be concluded that plasma exchanges, associated with CsA, are an efficient experimental protocol in the rat to increase the survival time of guinea pig heart xenografts. The effect of the treatment is correlated with the decrease in natural cytotoxic antidonor antibodies.
Free jejunal autografting is increasingly recognized as a safe procedure of pharyngoesophageal reconstruction with good functional results, following circular total pharyngolaryngectomy for extended tumors of the pharynx or larynx. Very often, past history of irradiation and/or surgery of the neck have created severe atheromatous lesions of the cervical vessels. We report the case of a patient with obliteration of the right carotid artery and large recurrence of a tumor of the larynx in which simultaneous arterial venous bypass and free jejunal autograft were performed for pharyngoesophageal reconstruction.
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An experimental study was conducted in the rat to evaluate the sensitivity of the liver to hyperthermia and ischemia. A 15-min asanguineous isolated hyperthermic in vivo perfusion of the liver was done in rats with a normal liver and in rats with an hepatocarcinoma induced by chronic 3'-diethylaminoazobenzene intoxication. The perfusion was made using various ranges of temperature of the perfusate. In normal rats, the in vivo perfusion was well tolerated as long as the mean intrahepatic temperature remained under 38 degrees C. Postoperative evolution of serum transaminase level was similar whatever the temperature of the perfusate. Histological lesions of the hepatic parenchyma were as severe as the temperature of the perfusate was elevated. In rats with tumors, the mortality rate was elevated in the animals with large tumors. A moderate decrease in the serum alpha-fetoprotein level was observed during the first days after liver perfusion. In all cases, death occurred apparently as a direct consequence of liver injury. This study defines the sensitivity of the normal or neoplastic rat liver to hyperthermia and ischemia using a model of isolated in vivo perfusion of the liver. It provides a basis for further investigations on the effect of hyperthermia on experimental liver tumors.
In cirrhosis, the phagocytic function of the reticuloendothelial system (RES) is decreased. In order to investigate the mechanisms of the hepatic reduced phagocytic activity present in cirrhosis, the hepatic and splenic uptake of 51Cr sheep red blood cells (SRBC) and of colloidal carbon was measured in three groups of Sprague-Dawley rats. Group 1 consisted of 42 control rats, group 2 of 36 rats with end-to-side portacaval shunt and group 3 of 24 rats with carbon tetrachloride-induced cirrhosis. The hepatic uptake of 51Cr SRBC and of colloidal carbon was significantly (p less than 0.001) reduced in cirrhotic rats (group 3). Conversely, in rats with a portacaval shunt and a noncirrhotic liver (group 2), the hepatic uptake of 51Cr SRBC was moderately reduced, whereas the colloidal carbon hepatic uptake was not found to be decreased. These results suggest that the decreased RES phagocytic activity observed in cirrhotic rats is only partially due to portacaval shunt and that an intrinsic defective activity of hepatic phagocytic cells is probably present.
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A technique is described for orthotopic liver transplantation in the rat using polyethylene cuffs to re-establish subhepatic cava and portal vascular anastomoses. This procedure reduces the time of portal clamping, an important factor of survival. The method was employed in 247 animals during studies to evaluate allograft tolerance and rejection mechanisms in rats of pure strain.
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The purpose of this study was to compare the results of two therapeutic methods used in an emergency to control oesophageal variceal bleeding resistant to medical treatment in cirrhotic patients: portal diversion (116 patients) or transhepatic embolization of the varices (84 patients). Portal diversion proved more effective in stopping the haemorrhage than embolization but the overall mortality rate was about the same with the two procedures. An analysis of the results taking into account the patient's condition failed to show any difference in mortality between the two methods. Indeed, the very high mortality rate in the most severely ill patients may oblige to question their usefulness in such cases. In the least severe patients, we prefer portal diversion which is quicker and can be performed at any time. In patients of the intermediate group transhepatic embolization seems to be less hazardous than portal diversion.
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In this study, the beneficial effect of intrasplenic transplantation of hepatocytes or splenocytes was shown in animals with 75% hepatectomy and portacaval shunt but not in animals with total dehepatization by hepatic vascular exclusion. No enhancement of the phagocytic activity was observed in the animals with 75% hepatectomy and portacaval shunt after injection of hepatocytes or splenocytes. This study confirms the efficacy of hepatocytes for the treatment of experimental liver failure but shows that nonhepatic cells may be equally as effective. Metabolic activity of the transplanted cells and stimulation of the phagocytic activity of the reticuloendothelial system probably do not explain the therapeutic effect of the transplanted cells.
A technique for orthotopic hepatic transplantation in the rat uses polyethylene cuffs to re-establish vascular and biliary continuity. Introduction of the suprahepatic cuff into the intrahepatic vena cava of the receiver rat, after partial hepatectomy, reduces the duration of vascular clamping and improves survival of grafted rats (long-term survival: 70%). This technique is simple to reproduce after several weeks of training and can allow research teams to study immunologic mechanisms of tolerance or rejection of liver allografts in the pure strain rat.