H. Bismuth

Transplantation of hepatocytes for treatment of surgically induced acute hepatic failure in the rat.

Efficacy of transplanted hepatocytes was evaluated in rats with a surgically induced acute hepatic failure. After 75% liver resection and portacaval shunt, the intrasplenic or intraperitoneal injection of 20 million isolated fresh hepatocytes was shown to significantly reduce the mortality rate. These results confirm that the transplantation of isolated hepatocytes may prevent death in rats with acute hepatic failure, and suggest that hepatocyte transplantation acts by a mechanism of hepatic support.

Therapeutic Efficacy of the Transplantation of Isolated Hepatocytes in Rats with Surgically Induced Acute Hepatic Failure: A Study of the Mechanism

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.

Surgically Induced Acute Hepatic Failure in the Rat

Several surgical procedures were tested in the rat in order to create a spontaneously lethal but potentially reversible acute hepatic failure. Two combined surgical procedures fulfill these conditions: 75% hepatectomy plus portacaval shunt and 85% hepatectomy plus 30-min clamping of the celiac and superior mesenteric arteries. These two procedures should constitute useful tools for the evaluation of new methods of hepatic support.

Decreased Reticuloendothelial Phagocytic Capacity in Cirrhotic and Portacaval Shunt Rats

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.

Does Hepatic Blood Flow Decrease after Portal-Systemic Shunt?

The precise effect of portacaval shunt upon liver blood flow is still under discussion. In the present work, the consequences of portal-systemic shunt on hepatic blood flow were investigated in rats w

EFFECT OF PHENOBARBITAL IN A CASE OF EXTRAHEPATIC CHOLESTASIS

Phenobarbital was administered to a patient with extrahepatic biliary obstruction who was initially thought to have cholestatic hepatitis. On two occasions, administration of the drug was associated with a decrease of jaundice, pruritus, and serum bile acid levels. This strongly suggests that phenobarbital may be effective not only in intrahepatic cholestasis, as reported earlier, but also in extrahepatic obstruction, and therefore cannot be used for the differention of these two types of cholestasis.

Spontaneous Long-Term Survival of Liver Allografts in Inbred Rats: Comparison between Semi-Allogeneic and Fully Allogeneic Strain Combinations

Spontaneous tolerance of liver allografts can be observed in inbred rats. In order to study the influence of the density of major histocompatibility complex alloantigens on the fate of liver allografts in the rat, liver allografts were performed in a semi-allogeneic and a fully allogeneic combination. Comparisons of the fate of heart and kidney allografts were made in the same combinations. A similar proportion of spontaneously tolerated liver allografts was observed in the two combinations; after a few months these animals were in a state of donor-specific unresponsiveness. A spontaneous prolongation of kidney allografts was observed only in the semi-allogeneic combination. These animals were not in a state of donor-specific unresponsiveness. These results suggest that induction of liver allograft tolerance in the rat is not decisively influenced by the importance of the density of major histocompatibility complex antigens present on the graft and that its mechanism may be different from that which causes spontaneous prolongation of semi-allogeneic kidney allografts.

Early Recovery of Albumin Synthesis after Liver Transplantation

The delay necessary for an orthotopic transplanted liver to recover in normal activity has never been defined. This is of great importance whenever liver transplantation is considered in patients with severe liver insufficiency. This delay was studied in dogs using albumin synthesis and BSP clearance as tests of liver function. Albumin synthesis was normal as early as 2 h following graft revascularization while BSP clearance was not yet normal by this time. It is suggested that transplanted livers will be rapidly able to corect metabolic disorders and above all coagulation problems in patients with terminal hepatic failure.

Effects of hyperthermia on normal or neoplastic rat liver

An experimental study was conducted in rats to evaluate the sensitivity of the liver to infrared hyperthermia. A 15-min hyperthermia session treating only the liver was done in rats with a normal hepatic parenchyma and in rats with hepatocarcinoma induced by chronic 3-diethylaminoazobenzene intoxication, at various ranges of intrahepatic temperature. In normal rats, 40-42 degrees C hyperthermia was well tolerated, but the mortality rate increased when the intrahepatic temperature exceeded 42 degrees C. In rats with tumors, a 40-42 degrees C hyperthermia session was well tolerated in case of small tumors, but resulted in a high mortality rate in case of large tumors. In all cases, death occurred as a consequence of liver injury. This study using a simple method of hyperthermia defines the thermosensitivity of the neoplastic or normal rat liver and provides a basis for further investigations on the effect of hyperthermia on experimental liver tumors.

Canine Intrathoracic Hepatic Homograft: A Life-Supporting Procedure

At the present time, no technique of heterotopic liver transplantation is capable of sustaining life in reproducible fashion unless portal blood is supplied to the graft. However, suppression of the portal blood risks compromising the function and eventual regeneration of the host liver, particularly if such a technique is to be used in the treatment of acute hepatic failure. The failure of heterotopic hepatic transplantation without portal blood may be due in part to unfavorable hemodynamic conditions. Livers grafted by a technique of intrathoracic homograft that aims to reproduce hemodynamic conditions close to the normal as regards inflow and venous drainage are capable of maintaining life in the hepatectomized dog.