Influence of antithrombin on ischemia/reperfusion injury in the isolated blood-free perfused rat heart

Introduction: Antithrombin (AT) is well known as an important inhibitor of the coagulation system. An interesting new hypothesis is that antithrombin exerts specific anti-inflammatory effects by stimulating the production of prostacyclin in endothelial cells. Recent studies report beneficial influence on ischemia/reperfusion injury in several organs. These effects are independent of the coagulation system. We investigated the influence of antithrombin on ischemia/reperfusion injury and prostacyclin release in the isolated rat heart. Since the perfusion of the hearts was without blood, the used model essentially describes effects of antithrombin on endothelial cells. Material and methods: Experiments were performed using the temperature-controlled and pressure-constant Langendorff apparatus. The hearts of 32 male Sprague-Dawley rats were subjected to 20 min of global ischemia followed by 30 min of reperfusion. Antithrombin was administered in three different concentrations (1, 4 and 8 U/ml) 15 min prior to global ischemia. Cardiac contractility parameters and biochemical parameters were measured. Results: Treatment with antithrombin did not increase the release of prostacyclin significantly after ischemia. Antithrombin at a concentration of 8 U/ml led to a significant increase in creatine kinase (CK; p < 0.05) and troponin I (p < 0.05), whereas measurements of lactate dehydrogenase (LDH) revealed no significant differences between treated and untreated hearts. Conclusion: Our study shows that antithrombin did not reduce ischemia/reperfusion injury in the isolated heart, and prostacyclin is not significantly released following antithrombin treatment. High concentrations of antithrombin, however, might have a negative influence on the reperfused heart. The underlying mechanism remains unclear. (C) 2003 Elsevier Science Ltd. All rights reserved.