ADENOSINE-A2-RECEPTOR ACTIVATION AT REPERFUSION REDUCES INFARCT SIZE AND IMPROVES MYOCARDIAL WALL FUNCTION IN DOG HEART

Reestablishment of blood supply to ischemic myocardium leads to bioche mical and cellular changes which are believed to reduce the amount of potentially salvageable myocardium (reperfusion injury). In this situa tion, adenosine is known to have myocardial protective properties. Act ivation of adenosine A2-receptors may account for most of the benefici al effects of adenosine in reperfusion injury because A2-receptor acti vation mediates vasodilation, inhibits neutrophil adhesion to vascular endothelium and diminishes generation of free radicals by neutrophils , thus acting on some of the key mechanisms of reperfusion injury such as postischemic vascular dysfunction and neutrophil-mediated damage. Therefore, we investigated the effect of an intracoronary A2-agonist, CGS 21680, on regional postischemic myocardial function (measured as w all thickening) and infarct size [determined by triphenyltetrazolium c hloride (TTC) staining]. Fourteen anesthetized open-chest dogs underwe nt 1-h left anterior descending artery (LAD) occlusion and 6-h reperfu sion and were randomly assigned to receive intracoronary CGS 21680 or to serve as control. The drug was infused for 60 min starting 5 min be fore reperfusion with a concentration of 10(-7) M at a rate of 10 ml/m in under anoxic conditions. The infusion was then continued for the fi rst 55 min of reperfusion with 10(-6) M at a rate of 1 ml/min. Intraco ronary infusion of CGS 21680 led to significant improvement in regiona l wall function in postischemic myocardium (p < 0.05 vs. control). Thi ckening fraction (percentage of baseline) increased from - 13.1 +/- 13 .7% (mean +/- SD) during occlusion to 15.3 +/- 29.8% at 30 min of repe rfusion in the CGS 21680 treatment group and remained at this level th roughout the reperfusion period. In the control group, thickening frac tion was - 23.7 +/- 16.2% during occlusion and did not recover during reperfusion. A significant reduction in infarct size was noted in the treatment group (11.5 +/- 7.9% of area at risk) as compared with the c ontrol group (28.6 +/- 11.4%, p < 0.05). These findings support the hy pothesis that the protective effect of adenosine on reperfusion injury is not due to replenishment of the nucleoside pool but rather is indu ced by stimulation of the adenosine A2-receptor.