The release of cytokines, adhesion molecules, and extracellular matrix parameters during and after reperfusion in human liver transplantation.

Poor initial graft function may increase postoperative morbidity including the risk of early allograft rejection. Various mediators, including immunostimulatory cytokines, may be released during reperfusion in relation to the extent of preservation and reperfusion injury. For this purpose, 81 patients with 85 liver transplants were monitored for cytokines, adhesion molecules, extracellular matrix (ECM) parameters, and neopterin at predefined time-points during and after transplantation. To estimate the origin of cytokine release, blood was obtained central and hepatic venously for the first 48 hr after reperfusion and subsequently from a peripheral vein. One-year patient survival was 88.9%; no relation to initial graft function was observed. Poor initial graft function failed to increase the risk for subsequent infectious complications but was associated with an increased risk of early allograft rejection. The incidence of steroid-resistant rejection was significantly increased in patients with poor initial graft function (35.7% versus 12.7% in patients with good and moderate initial graft function; P < or = 0.05). Various cytokines, adhesion molecules, and ECM parameters including sTNF-RII, sIL-2R, IL-8, IL-10, sVCAM-1, E-selectin, hyaluronic acid, sialic acid, and laminin correlated significantly with the extent of preservation and reperfusion injury. Although none of these parameters was more appropriate in determining the extent of preservation and reperfusion injury than currently established parameters (AST, ALT, and color and amount of bile production), the combined increase in these parameters may not only promote tissue repair but may also perpetuate liver allograft injury and thereby cause significant morbidity. Besides cytokines and adhesion molecules, the ECM may play a pivotal role in determining repair or ongoing tissue injury. Ongoing changes at the microvasculature and basement membrane may result in an increase of local and circulating cytokines and adhesion molecules, which increase the risk of subsequent early allograft rejection. Furthermore, the increase in sTNF-RII, E-selectin, and laminin during reperfusion was predictive of subsequent development of acute allograft rejection. These observations may be of value for further strategies to decrease reperfusion injury and prevent early allograft rejection.

Dopamine, dopexamine and dobutamine in liver transplant recipients: a comparison of their effects on hemodynamics, oxygen transport and hepatic venous oxygen saturation.

The purpose of this study was to determine the effects of vasoactive treatment with dopamine (DO), dopexamine (DX), and dobutamine (DOB) on hemodynamics, oxygen transport and hepatic venous oxygen saturation (SvhO2) after orthotopic liver transplantation (OLT). A pulmonary artery catheter was inserted into the right hepatic vein of 17 OLT patients. Timed infusion of DO, DX, and DOB was performed at the following rates: DO at 4 and 8 micrograms/kg per minute, DX at 4 and 8 micrograms/kg per minute, and DOB at 5 and 10 micrograms/kg per minute. Hemodynamics, oxygen transport variables, and SvhO2 were assessed. Each catecholamine induced a significant increase in cardiac index, oxygen delivery, and SvhO2. Mean arterial pressure was increased during DO and DOB, but significantly reduced during DX. Each inotrope increased oxygen delivery in parallel with SvhO2, suggesting a corresponding increase in hepatic oxygen supply. Therefore, it appears that each vasoactive drug may be utilized in OLT patients to provide oxygen delivery without impairment of splanchnic oxygenation.

[Somatotropin, antidot against phalloidin (author's transl)]. / Somatotropin, Antidot gegen Phalloidin.

1. Somatotropin protects rats against a lethal dose of phalloidin (1.3 mg/kg). 2. Scanning electron microscopy has shown that 2 hours after phalloidin injection the liver from a somatotropin-pretreated rat is not significantly different to that from an untreated rat. Phalloidin alone caused complete destruction of the structure of the liver lobules. 3. Somatotropin does not prevent phalloidin uptake by the liver but slows down elimination. 4. The findings are discussed with respect to their therapeutic possibilities as somatropin protects rats against death also after phalloidin poisoning.