REGULATION OF THE COMPLEMENT CASCADE BY SOLUBLE COMPLEMENT RECEPTOR-TYPE-1 - PROTECTIVE EFFECT IN EXPERIMENTAL LIVER ISCHEMIA AND REPERFUSION

The complement cascade was inactivated in a model of rat liver ischemi a with the purpose of studying the role of complement in tissue injury after ischemia and reperfusion. Soluble human complement receptor typ e 1 (sCR1) was administered either in a single dose of 25 mg/kg or in 2 doses of 50 mg/kg i.v, over 24 hr after vascular occlusion. Sham ope rated rats, nontreated rats submitted to liver ischemia, and rats pret reated with cobra venom factor and submitted to liver ischemia were us ed as controls. This experiment consists of the temporary interruption of arterial and portal blood flow to the left lateral and medial lobe s of the liver for 45 min, followed by a 24-hr period of follow-up aft er reperfusion. Liver blood flow and hemoglobin saturation were record ed for 1 hr after declamping, with statistically significant differenc es between the experimental groups and the untreated control group, wh ich received liver ischemia (P<0.001). At 24 hr, galactose elimination was assayed as a liver function test; it was significantly better in the sCR1-treated rats when compared with control rats submitted to isc hemia (P<0.01). Alanine aminotransferase levels were also significantl y lower in the sCR1-treated rats at 6 and 24 hr (P<0.05), Complement a ctivity was reduced to 25% and 12.5% of normal rats with the respectiv e doses of sCR1. Immunoperoxidase stainings for C3 and C9 were perform ed on liver sections; they showed endothelial deposits of C3 and C9 in the control group subjected to ischemia. Few C3 deposits were present in the sCR1 (25 mg/kg)-treated rats, but not in the cobra venom facto r or sCR1 (50 mg/kg) groups. These results confirm that complement is inactivated by sCR1 with amelioration of reperfusion injury in the rat liver.