Differential effects of heparin on the early and late phases of hepatic ischemia and reperfusion injury in the pig

The mechanisms by which heparin protects the liver during induced episodes of liver ischemia-reperfusion are poorly understood. Previous work in a swi ne model demonstrated that serum levels of glycohydrolases and lipid peroxi de peaked within 3 h after 45 minutes of hepatic ischemia followed by reper fusion. Serum levels of lactate dehydrogenase and aspartate aminotransferas e peaked 20-24 h later. The aim of this study was to evaluate the effect of heparin on these two-phases of enzyme release, using a pig model of hepati c ischemia-reperfusion injury. Twenty male swine were divided into control (n = 8) and heparin (n = 12) groups. In the heparin group, heparin was admi nistered prior to and concurrent with ischemia-reperfusion. Following 45 mi n of hepatic ischemia, the levels of beta-galactosidase, beta-glucosidase, acid phosphatase, purine nucleoside phosphorylase, lipid peroxides, lactate dehydrogenase, and aspartate aminotransferase in serum were monitored for up to 166 h and compared to pre-ischemic and control levels. With heparin i nfusion, the peak levels of beta-galactosidase, beta-glucosidase, and the l ipid peroxide were reduced to 50-60% of the control levels. Acid phosphatas e and purine nucleoside phosphorylase activities in serum were reduced to 2 5% and 60%, respectively. The peak concentrations of lactate dehydrogenase and aspartate aminotransferase were reduced to about 25% of the control lev el. In addition, the serum enzymes of control pigs did not return to pre-is chemic levels until 2 weeks after hepatic ischemia, while they normalized i n less than 1 week in the heparin-treated animals. Systemic heparinization had different protective effects on the first and secondary phases of liver injury. These differences may reflect heparin protection of different type s of liver cells. The protection of the parenchymal cells may be the combin ed result of reduced sinusoidal cell injury and the anticoagulant propertie s of heparin.