REDUCTION OF MYOCARDIAL REPERFUSION INJURY BY INTRAVENOUS ADENOSINE ADMINISTERED DURING THE EARLY REPERFUSION PERIOD

Adenosine influences the function of several cell types though to be involved in the pathogenesis of myocardial reperfusion injury. We have previously demonstrated that intracoronary administration of adenosine enhances myocardial salvage 24 hours after reperfusion. To determine if these beneficial effects could be obtained during a prolonged period of reperfusion using an intravenous route of administration, 22 closed-chest dogs were subjected to 90 minutes of proximal left anterior descending coronary artery occlusion and 72 hours of reperfusion. Animals randomly received either intravenous adenosine (0.15 mg/kg/min) or an equal volume of Ringer's lactate during the first 150 minutes of reperfusion. The area at risk was defined in vivo with Monastral blue, and infarct size was measured histologically with Mallory's trichrome stain. Serial global and regional ventricular function were determined with contrast ventriculography and analyzed using a computerized radial shortening method. Biopsies were obtained from the central ischemic zone to assess endothelial ultrastructure and capillary obstruction. No significant effects in heart rate or blood pressure were noted during adenosine infusion. Transmural collateral blood flow during ischemia was similar in the groups. Infarct size expressed as a percentage of the anatomical area at risk was significantly less in the adenosine-treated group (35.3% +/- 4.3% in controls versus 17.1 +/- 4.3% in treated animals, p < 0.01). A progressive decrease in transmural blood flow was notes in control animals during reperfusion, resulting in a significant reduction at 3 hours compared with the preocclusion value (0.69 +/- 0.11 ml/min/g [at baseline versus 0.45 +/- 0.10 ml/min/g at 3 hours, p < 0.05]). In contrast, flow in adenosine animals at 3 hours was similar to baseline values (0.91 +/- 0.15 ml/min/g at baseline versus 0.98 +/- 0.14 ml/min/g at 3 hours, p = NS) and was significantly higher (p < 0.05) than the control group. Radial shortening in the ischemic zone was significantly improved at 3 (- 2.6 +/- 2.8% in controls versus 11.6 +/- 3.3% in treated animals, p < 0.01) and 72 hours (5.5 +/- 2.0% in controls versus 17.3 +/- 3.5% in treated animals, p < 0.01) after reperfusion in treated animals. Electron microscopy showed reduced neutrophil and erythrocyte plugging of capillaries with relative preservation of endothelial cell structure in the adenosine group. This study demonstrates that intravenous administration of adenosine during the early reperfusion period results in a sustained reduction in myocardial infarct size associated with preservation of regional ventricular function. Although the exact mechanisms remain to be elucidated, results from this study suggest that the beneficial effects of the drug persist for a prolonged period after reperfusion.