Myocardial Stunning in Dogs

This study was undertaken to elucidate whether cal-adrenoceptor activity is beneficial to contractile dysfunction during reperfusion after a brief period of ischemia (stunned myocardium) in 54 open-chest dogs. Contractile dysfunction assessed by fractional shortening (FS) was observed 3 hours after the onset of reperfusion following 15 minutes of complete occlusion of the left anterior descending coronary artery. Pretreatment with prazosin (4 ,ug/kg/min i.c.) further deteriorated contractile dysfunction compared with the untreated condition (12.7±0.6% versus 6.9+0.4% with prazosin treatment, p<0.001). Conversely, atl-adrenoceptor agonists, methoxamine (1.0 ,g/kg/min i.c.) and norepinephrine (0.24 ,ug/kg/min i.c.) with rauwolscine and propranolol, significantly attenuated contractile dysfunction (FS in the methoxaminetreated group, 17.3+±0.3%, p<0.001 versus the untreated group; FS in the norepinephrinetreated group, 18.00.9%o,p<0.05 versus 13.6±1.1% in the propranolol group). Both adenosine release and hyperemic coronary flow response during the early reperfusion period were significantly attenuated in the prazosin-treated group. and both were enhanced in the al-adrenoceptor stimulation groups. These results suggest that beneficial effects of aladrenoceptor activity may be due to the enhanced release of adenosine. To test the cause-effect relation between the extent of adenosine release and contractile dysfunction during reperfusion, 8-phenyltheophylline was infused to block adenosine receptors in the methoxamine-treated group. The treatment with 8-phenyltheophylline completely abolished (FS, 7.4+0.3%) the beneficial effect of the enhanced adenosine release by cvl-adrenoceptor stimulation. Furthermore, in the prazosin-treated group, adenosine (9 .ug/kg/min) was additionally infused into the left anterior descending coronary artery 5 minutes before and 2 hours after the onset of reperfusion. Both hyperemic coronary flow and contractile dysfunction (FS, 17.3 +0.3%) recovered to the levels of the r1-adrenoceptor stimulation groups. However, treatment with papaverine could not prevent deleterious effects of prazosin despite the fact that comparable hyperemic flow was obtained. Instead, lactate production up to 10 minutes after the onset of reperfusion was significantly larger (p<0.01) despite augmented contractile function in the prazosin-treated and the 8-phenyltheophylline with methoxamine-treated groups compared with the untreated group. The electron microscopic examination revealed no irreversible myocardial injury with and without pharmacological interventions. Thus, we conclude that ael-adrenoceptor activity can reduce the magnitude of myocardial stunning and that its cellular mechanism is due to enhanced adenosine release by al-adrenoceptor activity. The metabolic effects of adenosine, in part, may mediate protective mechanisms for myocardial stunning rather than the coronary hyperemic flow response. (Circulation Research 1991;68:1322-1339)