INTRACORONARY SIN-1C DURING REPERFUSION REDUCES INFARCT SIZE IN DOG

Reperfusion of ischemic myocardium may aggravate the ischemic state of injury and thus augment infarct size (reperfusion injury). The aim of this study was to reduce infarct size by an intervention at the time of reperfusion that acts only on a reperfusion-specific pathomechanism . It was investigated whether SIN-1C, a metabolite of molsidomine, can protect against reperfusion injury in canine hearts in vivo. Ten anes thetized open chest dogs underwent 1 h of left anterior descendent art ery (LAD) occlusion and were randomly assigned to receive either Intra coronary SIN-1C or vehicle infusion as a placebo during the first hour of reperfusion. The infusion was adjusted to LAD flow to achieve a re gional blood concentration of 5.10(-3) M. Infarct size was assessed by triphenyltetrazolium staining after 6 h of reperfusion. Left ventricu lar pressure (LVP) was similar in both groups (SIN-1C: 101 +/- 6, plac ebo: 89 +/- 6 mm Hg, mean +/- SEM, n = 5) at the beginning of the expe riment and did not change significantly thereafter from baseline value s in both groups. During SIN-1C infusion, the LAD now was increased (S IN-1C: 195 +/- 38, control: 86 +/- 17 ml/min/100 g at 30 min of reperf usion, p < 0.05), while systemic hemodynamics remained unaltered. A re duction in infarct size (percent of area at risk) was seen in the SIN- 1C group (11.4 +/- 2.8%) compared with the placebo group (24.4 +/- 3.9 %, p < 0.05). Infusion of papaverine (5.10(-5) M) following an identic al protocol caused a similar vasodilation as SIN-1C, but did not reduc e infarct size in five additional dog experiments. Infusion of SIN-1C (2.5.10(-3) 10(-2) M) in normal myocardium in one additional dog showe d a dose-dependent increase in LAD flow to 270%, which was paralleled by a depression of regional wall thickening (33%). The results demonst rate that necrosis in the reperfused myocardium can be greatly reduced by therapeutic intervention at the onset of reperfusion. Intracoronar y SIN-1C can be used for such an intervention. It has a pronounced loc al protective effect, without altering systemic hemodynamics. The mech anism of protection does not seem to be related to the coronary vasodi latory effect of SIN-1C.