Beneficial effects of the alpha-adrenergic antagonist nicergoline during acute myocardial ischemia and reperfusion in the dog.
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.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000209:etiology; D001157:Arterial Occlusive Diseases / Q000150:complications; D002245:Carbon Dioxide / Q000097:blood; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000008:administration & dosage*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D009530:Nicergoline / Q000008:administration & dosage*; D010313:Partial Pressure; D010477:Perfusion / Q000009:adverse effects; D010656:Phenylephrine / Q000008:administration & dosage; D011312:Pressure; D014655:Vascular Resistance / Q000187:drug effects
D004873:Ergolines; D002245:Carbon Dioxide; D010656:Phenylephrine; D009530:Nicergoline