EFFECTS OF SUPPLEMENTATION WITH ILOPROST ON THE CARDIOPROTECTION BY BW755C - (A DUAL INHIBITOR OF CYCLOOXYGENASE AND LIPOXYGENASE ENZYMES) IN MYOCARDIAL REPERFUSION INJURY

The effect of BW755C (a dual inhibitor of cycle-and lipoxygenase enzym es) alone and in combination with iloprost (a PGI(2) analogue) on myoc ardial reperfusion injury was investigated in anaesthetised open-chest dogs. The left anterior descending coronary artery was occluded for a period of 40 min followed by reperfusion for 3 h. Dogs were administe red either saline, BW755C (10 mg kg(-1) slow bolus) or BW755C plus ilo prost (100 ng kg(-1)min(-1) for 75 min) just prior to reperfusion. The haemodynamic data showed significant reduction in MAP and both LV pea k-positive and peak-negative dP/dt following reperfusion in the saline -treated group, along with a delayed recovery of LVEDP. These changes were accompanied by significant depletion of myocardial ATP and glycog en stores. Administration of BW755C prevented the haemodynamic changes and replenished the HEP stores. Although coadministration of iloprost with BW755C afforded early normalisation of LVEDP and LV peak positiv e dP/dt, but MAP and LV peak negative dP/dt remained significantly dep ressed. Therefore, it might be concluded from this study that suppleme ntation of BW755C with iloprost may have deleterious haemodynamic effe cts on the reperfused myocardium, particularly in the doses used. (C) 1997 The Italian Pharmacological Society.