Potential interactions between iloprost and SIN-1 on platelet aggregation and myocardial infarct size in vivo

Nitric oxide and prostacyclin are endothelial-derived vasodilators which in hibit platelet aggregation in a synergistic manner. Experiments were design ed to examine whether 3-morpholino-sydnonimine (SIN-1) and iloprost have sy nergistic cardioprotective actions and whether their effects on infarct siz e are related to inhibition of platelet aggregation. Anaesthetized rabbits (n = 9-10 per group) were subject to 40 min myocardial ischaemia followed b y 3 h reperfusion. Infarct size (percentage of area at risk) was not altere d significantly by 3 mu g kg(-1) min(-1) SIN-1 (29.7 +/- 1.9%), but was red uced by 0.03 mu g kg(-1) min(-1) iloprost (24.6 +/- 1.6%) and to a greater extent by the combination of SIN-1 and iloprost (18.8 +/- 1.7%), compared t o controls (33.6 +/- 4.7%). In control rabbits, there were reductions in th e ex vivo aggregation of platelets in response to ADP or collagen after isc haemia and reperfusion. SIN-1 and iloprost caused some alterations in plate let responses, but combined administration of both drugs did not produce gr eater effects. Although the reduction in myocardial infarct size was greate st with both drugs, this did not appear to be a synergistic interaction and was not dependent on the effects of the drugs on haemodynamics or platelet aggregation. (C) 1999 Elsevier Science B.V. All rights reserved.