BASIC ANATOMICAL AND PHYSIOLOGICAL DIFFERENCES BETWEEN SPECIES SHOULDBE CONSIDERED WHEN CHOOSING COMBINATIONS FOR USE IN MODELS OF HEPATICXENOTRANSPLANTATION - AN INVESTIGATION OF THE GUINEA-PIG TO RAT COMBINATION

Published data on the guinea pig-to-rat hepatic xenotransplant model d escribe problems concerning poor graft reperfusion, To further investi gate this phenomenon, orthotopic liver xenotransplantation be. tween w eight-matched guinea pigs and rats were performed using Kamada's techn ique. On reperfusion, all cases had portal venous inflow block. with h ypoperfusion of the hepatic parenchyma. Histological examination showe d no evidence of hyperacute rejection, although deposits of IgG2a and C3 but not IgM were identified within the central area of the liver. T o increase blood inflow, arterialized partial liver grafts were perfor med without changing the outcome. We hypothesize that the hypoperfusio n may be related to anatomical and physiological differences between t he species. Guinea pig portal vein branches were found to have muscula r walls susceptible to spasm, and portal blood flow is four times grea ter in the guinea pig than in the rat because the guinea pig intestine is both longer (two times as long) and of greater diameter. The combi nation of reperfusion injury, early immunological events, and the rat' s lower portal blood flow induces spasm of the intrahepatic portal sys tem resulting in hypoperfusion. These findings demonstrate the importa nce of recognizing basic anatomical and physiological differences betw een species when selecting xenotransplantation models.