Beneficial effects of the alpha-adrenergic antagonist nicergoline during acute myocardial ischemia and reperfusion in the dog

Abstract

Recent experimental and clinical data have stimulated interest in the use of α-adrenergic antagonists in acute myocardial infarction. We evaluated nicergoline, a new relatively selective α 1-antagonist which uniquely lowers heart rate. Open-chest dogs, randomized to control (n = 25) or intravenously treated group (n = 20; 0.5 mg/kg bolus, then 0.10 to 0.15 mg/kg/min), underwent coronary artery occlusion (CAO) followed after 25 minutes by coronary artery reperfusion (CAR). Nicergoline decreased heart rate by 47 ± 5 bpm and mean aortic pressure by 39 ± 4 mm Hg. Following CAO, nicergoline reduced total coronary collateral resistance (radiolabeled microspheres; 698 ± 75 vs 2167 ± 530 mm Hg/ml/min/gm, p < 0.05), increased the ischemic zone/nonischemic zone flow ratio (0.14 ± 0.04 vs 0.06 ± 0.02, p < 0.05), and reduced the rise in intramyocardial CO 2 tension in the ischemic zone (mass spectrometry, p < 0.001). Furthermore, the drug decreased the rate of ventricular tachycardia (VT; 191 ± 13 vs 243 ± 3 bpm, p < 0.001) and the incidence of ventricular fibrillation (VF; 1 of 20 [5%] vs 7 of 25 [28%], p < 0.05). Following CAR, nicergoline did not significantly reduce the incidence of VF but did lower rate (154 ± 8 vs 212 ± 10 bpm, p < 0.001) and incidence ( p < 0.05) of VT. Thus nicergoline reduced severity of ischemia and afforded protection against arrhythmias induced by myocardial ischemia and reperfusion. The observed reduction in heart rate may have contributed importantly to these beneficial effects. Clinical investigation of this potentially useful vasodilator seems warranted.