Effects of alpha-adrenergic blockade on regional myocardial function in canine ischemic myocardium during beta-adrenergic blockade.

OBJECTIVE

The contribution of alpha-adrenergic receptor subtypes in mediation of coronary vasoconstriction during ischemia remains controversial. This study investigated the effects of alpha-adrenergic subtypes blockade on regional myocardial function in a canine ischemic model.

DESIGN

Prospective, randomized, controlled trial.

SETTING

Experimental animal laboratory in a university medical center.

PARTICIPANTS

Thirty-two adult dogs, weighing 13 to 22 kg.

INTERVENTIONS

The animals were prepared with pentobarbital, oxygen, enflurane and pancuronium. Two selective alpha 1-adrenergic antagonists (bunazosin, 50 micrograms/kg/min, n = 8, and prazosin, 25 micrograms/kg/min, n = 8) and the alpha 2-adrenergic antagonist (yohimbine, 15 micrograms/kg/min, n = 8) were administered after the partial occlusion of the left circumflex coronary artery (LCX) during beta-adrenergic blockade (propranolol, 1 mg/kg).

MEASUREMENTS AND MAIN RESULTS

Myocardial systolic segment shortening (%SS) and a myocardial lactate extraction ratio (LER) were used as indices of regional myocardial and metabolic function. Compared with poststenotic condition, coronary blood flow of the LCX was increased by 123% with bunazosin and 138% with prazosin (p < 0.05, respectively). Both %SS and LER in the ischemic myocardium were significantly improved after treatment with both alpha 1-adrenergic antagonists (in the bunazosin group, %SS, 8.3 +/- 1.9 to 10.4 +/- 2.2%, p < 0.05; LER, -12.8 +/- 12.3 to 6.2 +/- 15.9%, p < 0.01; in the prazosin group, %SS, 8.5 +/- 1.6 to 10.3 +/- 1.9%, p < 0.05; LER, -10.2 +/- 5.7 to 3.6 +/- 10.2%, p < 0.05). In contrast, coronary blood flow of the LCX, %SS and LER were not different from poststenotic condition during alpha 2-adrenergic receptor blockade with yohimbine. The salutary effect of bunazosin was also observed after mechanically controlling for the afterload reduction produced by alpha 1-adrenergic blockade (n = 8). Prazosin and yohimbine were found to produce a significant increase in plasma norepinephrine levels in contrast to bunazosin, which had no significant effect.

CONCLUSIONS

These data indicate that alpha 1-adrenergic blockade increases coronary blood flow and improves regional myocardial function during myocardial ischemia.