Recent experimental and clinical data have stimulated interest in the use of
alpha-adrenergic antagonists in acute
myocardial infarction. We evaluated
nicergoline, a new relatively selective alpha 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 less than 0.05), increased the ischemic zone/nonischemic zone flow ratio (0.14 +/- 0.04 vs 0.06 +/- 0.02, p less than 0.05), and reduced the rise in intramyocardial CO2 tension in the ischemic zone (mass spectrometry, p less than 0.001). Furthermore, the
drug decreased the rate of
ventricular tachycardia (VT; 191 +/- 13 vs 243 +/- 3 bpm, p less than 0.001) and the incidence of
ventricular fibrillation (VF; 1 of 20 [5%] vs 7 of 25 [28%], p less than 0.05). Following CAR,
nicergoline did not significantly reduce the incidence of VF but did lower rate (154 +/- 8 vs 212 +/- 10 bpm, p less than 0.001) and incidence (p less than 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.