Limitation of myocardial unperfused area and necrotic zone 24 hours and 7 days after coronary artery ligation in rats by the stable prostacyclin analogue iloprost

Abstract

Protective effects of prostacyclin (PGI 2) and Iloprost in experimental cardiac ischemia are reported by several authors. However, the effects of continuous administration on the final outcome of myocardial infarction are not yet known. We investigated the effects of Iloprost on cardiac unperfused area (UA) and necrotic zone (NZ) as assessed by Evans blue perfusion and extraction and nitrobluetetrazolium staining, respectively, using osmotic minipumps for continuous intravenous drug administration. Starting 3–4 hours after left descending coronary artery-ligation (LAD-L) Iloprost was infused at doses of 0.1 μg and 0.5 pg · kg −1 · min −1. While the lower dose is below pharmacological effect level, the higher dose in rats slightly lowered blood pressure and effectively inhibited platelet aggregation. LAD -L in control rats resulted in UA and NZ extending to 34.2 and 16.9 %, respectively, of total ventricular mass (VM) after 24 hours and 28.3 and 21.3 % of VM, respectively, after 7 days. At the dose of 0.1 pg · kg −1 · min −1 Iloprost was ineffective in reducing UA 24 hours after LAD-L. However, at 0.5 pg · kg −1 · min −1 Iloprost with UA and NZ of 16.3 and 8.4 % of VM, respectively, after 24 hours and 8.5 and 5.2 % of VM, respectively, after 7 days reduced the extension of myocardial infarction by approximately 50 % after 24 hours and 70 % after 7 days, as compared to controls. As assessed in unperfused ventricular tissue after LAD-L and normal myocardium of sham-operated rats following 24 hours of Iloprost infusion, myocardial tissue concentrations of Iloprost amount to approximately half of the plasma levels irrespective of LAD-L. It is concluded that the cardioprotective properties of the stable PGl 2 analogue Iloprost with continuous i.v. administration of a platelet aggregation inhibiting dose result in effective reduction of infarct size 24 hours and 7 days after LAD-L in rats.