Recent evidence suggests a cardioprotective effect of
adenosine in
myocardial 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
ischemia or after reperfusion, and (3) whether
adenosine preconditions against
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 left anterior descending coronary artery followed by 4 hours of reperfusion received an intracoronary infusion of either saline (group I [control], 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 III, n = 11). Regional myocardial function (assessed as systolic wall thickening) was similar in the three groups at baseline and during
ischemia. After reperfusion, dogs treated with
adenosine before, during, and after
ischemia (group II) demonstrated a significant improvement in the recovery of function that persisted throughout the 4 hours of reperfusion. 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
adenosine in group II could not be ascribed to differences in ischemic zone size, collateral flow during
occlusion, coronary flow after reperfusion, arterial pressure, heart rate, or other hemodynamic variables. In phase B of the study, dogs received an intracoronary infusion of either saline (group IV [control], n = 6) or
adenosine (4 mg/min from 40 to 10 minutes before occlusion [group V, n = 6]). Despite pretreatment with
adenosine, the recovery of function in group V was indistinguishable from that in the control group. This study demonstrates that (1) continuous administration of
adenosine before, during, and after
ischemia results in a significant and sustained attenuation of
myocardial stunning; (2) this improved recovery of function cannot be attributed to nonspecific variables, such as collateral flow during
coronary occlusion, coronary flow after reperfusion, or other hemodynamic factors, and therefore reflects a direct cardioprotective action of
adenosine; (3) the protection against stunning is lost or markedly diminished if
adenosine is given only at reperfusion; and (4) administration of
adenosine before
ischemia does not precondition the myocardium against the stunning induced by a 15-minute occlusion.(ABSTRACT TRUNCATED AT 400 WORDS)