Lack of Any Additional Benefit in Combining Aspirin with Iloprost in a Canine Model of Myocardial Reperfusion Injury

Abstract

The effects of iloprost infusion (100ng/kg/min for 75 min) alone and in combination with aspirin (3mg/kg IV bolus) were compared in a canine model of myocardial reperfusion injury. Regional ischemia of 40 min was produced by temporary occlusion of the left anterior descending coronary artery, after which the myocardium was reperfused for a period of 3 hours. Mean arterial pressure (MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP), positive (+) LVdP/dt max and negative (−) LVdP/dt max were monitored. Rate pressure product and (−) dP/dt/P max were also derived from the above. Myocardial tissue levels of adenosine triphosphate (ATP), creatine phosphate (CP), glycogen and lactate were estimated. Following reperfusion in the saline treated group, there was a significant fall in (i) MAP, (ii) (+) LVdP/dt max and (iii) (−) LVdP/dt max. LVEDP was corrected about 2 hours after reperfusion. Despite correction of lactate accumulation, ATP and glycogen were not restored although the CP store was replenished. The hemodynamic profiles in both iloprost and in combination treated groups were similar; (i) depressed MAP (particularly during iloprost infusion) without any significant change in HR (ii) no significant depression in (+) LVdP/dt max (iii) depression in (−) LVdP/dt max but not when corrected for lower P max and (iv) a significant reduction in the incidence of reperfusion arrhythmias. Similarly, in both the drug/s treated groups, ATP, CP and lactate were normalised although glycogen store was not restored. The results of this study indicate (i) cardioprotective effect of iloprost even when administered prior to reperfusion and (ii) no additional protective effect of combining iloprost and aspirin.