Reduction of visceral reperfusion injury by antithrombin III and aprotinin

Objective: Disturbance of hepatic microcirculation and leukocyte-endothelium interaction represents one of the leading mechanisms for postoperative organ dysfunction after warm visceral ischemia. Recent studies showed that pretreatment with antithrombin III (AT III) and aprotinin reduces leukocyte-endothelium interaction in ischemic small intestine and during extracorporal circulation in cardiac surgery. The aim of this study was to analyze the effects of ATIII and aprotinin on hepatic microcirculation after warm ischemia and reperfusion.

Methods: Warm hepatic ischemia was induced in male Wistar rats (n=6 each group) by temporary (60min) occlusion of the left liver lobe. Drug application was performed 30min prior to ischemia: A) ATIII group: 250 IU/100g body weight; B) Aprotinin group: 2700 KIU/100g body weight during 20min initially, followed by continous infusion of 670 KIU/h/100g body weight. Intravital microscopy was performed 30 minutes after reperfusion. Data are given as mean values±SD. Significance analysis was done by Wilcoxon-Mann-Whitney-U-test.

Results: The disturbance of hepatic microcirculation could be significantly reduced by pretreatment with ATIII and aprotinin. The leukocyte-endothelium interaction in hepatic sinusoids was significantly reduced in the ATIII group (35.78±1.25 vs. 47.44±3.19 stickers in controls). Leukocyte sticking in postsinusoidal venules was significantly inhibited in both groups (174, 80±9.16 and 185.22±8.83 vs. 217.19±15.70 in controls).

Conclusion: Analysis of intravital videomicroscopy showed that hepatic microcirculation and organ dysfunction after warm hepatic ischemia in rats could be significantly enhanced by AT III and aprotinin most likely by reducing leukocyte-endothelium interaction.