EFFECT OF ADENOSINE ON MYOCARDIAL STUNNING IN THE DOG

Recent evidence suggests a cardioprotective effect of adenosine in myo cardial ischemia and reperfusion. The present study was undertaken to determine (1) whether adenosine attenuates myocardial stunning, (2) if so, whether the beneficial effect of adenosine takes place during isc hemia or after reperfusion, and (3) whether adenosine preconditions ag ainst myocardial stunning. A total of 93 dogs were used. In phase A of the study, open-chest dogs undergoing a 15-minute occlusion of the le ft anterior descending coronary artery followed by 4 hours of reperfus ion received an intracoronary infusion of either saline (group I [cont rol], n=14), 2 mg/min adenosine from 30 minutes before occlusion until 1 hour after reperfusion (group II, n=10), or 2 mg/min adenosine from 2 minutes before reperfusion until 1 hour after reperfusion (group II I, n=11). Regional myocardial function (assessed as systolic wall thic kening) was similar in the three groups at baseline and during ischemi a. After reperfusion, dogs treated with adenosine before, during, and after ischemia (group II) demonstrated a significant improvement in th e recovery of function that persisted throughout the 4 hours of reperf usion. In contrast, in dogs treated only during the reperfusion period (group III), the recovery of function was not statistically different from that in control dogs. The enhanced recovery effected by adenosin e in group II could not be ascribed to differences in ischemic zone si ze, collateral flow during occlusion, coronary flow after reperfusion, arterial pressure, heart rate, or other hemodynamic variables. In pha se B of the study, dogs received an intracoronary infusion of either s aline (group IV [control], n=6) or adenosine (4 mg/min from 40 to 10 m inutes before occlusion [group V, n=6]). Despite pretreatment with ade nosine, the recovery of function in group V was indistinguishable from that in the control group. This study demonstrates that (1) continuou s administration of adenosine before, during, and after ischemia resul ts in a significant and sustained attenuation of myocardial stunning; (2) this improved recovery of function cannot be attributed to nonspec ific variables, such as collateral flow during coronary occlusion, cor onary flow after reperfusion, or other hemodynamic factors, and theref ore reflects a direct cardioprotective action of adenosine; (3) the pr otection against stunning is lost or markedly diminished if adenosine is given only at reperfusion; and (4) administration of adenosine befo re ischemia does not precondition the myocardium against the stunning induced by a 15-minute occlusion. The failure of adenosine to produce a beneficial effect when given only at reperfusion indicates that in t he 15-minute occlusion model, the nucleoside acts primarily by decreas ing the severity of ischemic injury rather than by mitigating reperfus ion injury.