HEPATIC MICROCIRCULATORY DISTRUBANCE DUE TO PORTAL VEIN CLAMPING IN THE ORTHOTOPIC RAT LIVER TRANSPLANTATION MODEL

Abstract

Most modifications and applications of the orthotopic rat liver transplantation (ORLT) model require clamping of the portal vein, thus leading to ischemia of the gut. The purpose of this study was to evaluate the effect of portal vein clamping during ORLT on hepatic microcirculation and leukocyte--endothelial interaction by intravital fluorescence microscopy. ORLT were performed following 1 hr of cold storage in EuroCollins solution without (standard group) and with insertion of a portojugular shunt (shunt group) to minimize intestinal ischemia. ORLT induced reduction of perfused sinusoids (83%) and velocity of leukocytes (311 +/- 4.5 microns/sec; mean +/- SEM) compared with nontransplanted controls (99% and 417 +/- 4.9 microns/sec). Portojugular shunt during ORLT improved hepatic microvascular perfusion (89% and 355 +/- 3.4 microns/sec; P less than 0.05). Furthermore, percentage of permanent and temporary adherent leukocytes decreased significantly when a portosystemic shunt was applied (from 33.5 +/- 1% to 22.1 +/- 1% and 19.7 +/- 1.2% to 14.0 +/- 0.9%; P less than 0.05). The results of the study reveal that intestinal congestion and reperfusion results in a rise in leukocyte adhesion to the sinusoidal wall and in disturbances of the hepatic microcirculation. It seems likely that increased endotoxin concentrations in the portal vein induce an activation of hepatic macrophages that subsequently cause release of chemoattractant mediators. In conclusion, side effects of intestinal ischemia during experimental liver transplantation surgery on liver function due to release of chemoattractant mediators should be considered when experimental data are transferred to clinical settings.