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 swine model demonstrated that serum levels of glycohydrolases and lipid peroxide peaked within 3 h after 45 minutes of hepatic ischemia followed by reperfusion. Serum levels of lactate dehydrogenase and aspartate aminotransferase 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 hepatic ischemia-reperfusion injury. Twenty male swine were divided into control (n = 8) and heparin (n = 12) groups. In the heparin group, heparin was administered prior to and concurrent with ischemia-reperfusion. Following 45 min 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 infusion, the peak levels of beta-galactosidase, beta-glucosidase, and the lipid peroxide were reduced to 50-60% of the control levels. Acid phosphatase and purine nucleoside phosphorylase activities in serum were reduced to 25% and 60%, respectively. The peak concentrations of lactate dehydrogenase and aspartate aminotransferase were reduced to about 25% of the control level. In addition, the serum enzymes of control pigs did not return to pre-ischemic levels until 2 weeks after hepatic ischemia, while they normalized in 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 types of liver cells. The protection of the parenchymal cells may be the combined result of reduced sinusoidal cell injury and the anticoagulant properties of heparin.
Liu
W
W
Department of Surgery, University of New Mexico, Albuquerque 87131, USA.
Pitcher
D E
DE
Morris
S L
SL
Pugmire
J E
JE
Shores
J T
JT
Ingram
C E
CE
Glew
R H
RH
Morris
D M
DM
Fry
D E
DE
D000135:Acid Phosphatase / Q000097:blood / Q000187:drug effects; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology*; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000187:drug effects; D008054:Lipid Peroxides / Q000097:blood; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011683:Purine-Nucleoside Phosphorylase / Q000097:blood / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D013552:Swine; D001616:beta-Galactosidase / Q000097:blood / Q000187:drug effects; D001617:beta-Glucosidase / Q000097:blood / Q000187:drug effects
D008054:Lipid Peroxides; D006493:Heparin; D007770:L-Lactate Dehydrogenase; D011683:Purine-Nucleoside Phosphorylase; D001219:Aspartate Aminotransferases; D000135:Acid Phosphatase; D001617:beta-Glucosidase; D001616:beta-Galactosidase