Effect of alpha-adrenergic blockade on arrhythmias induced by acute myocardial ischemia and reperfusion in the dog.
Studies in cats suggest alpha-adrenergic contributions to arrhythmias during myocardial ischemia and reperfusion. The validity of this concept in other species, however, remains uncertain. Thus, 106 chloralose-anesthetized open-chest dogs undergoing a 25 min coronary artery occlusion followed by reperfusion received saline (n = 52), prazosin (1 mg/kg, n = 26), phentolamine (5 mg/kg, n = 18), or phentolamine (same dose) + propranolol (1 mg/kg, n = 10). Alpha-blockade was confirmed by alpha-agonist dose-response studies. In phentolamine-treated dogs, arterial pressure and heart rate were kept constant to prevent exacerbation of ischemia. Control and treated groups were comparable with respect to variables known to affect arrhythmias, such as size of occluded and reperfused vascular beds, coronary collateral flow, severity of ischemia estimated from intramyocardial CO2 tension, and peak reactive hyperemia. During coronary occlusion, the number of single premature ventricular complexes was reduced by phentolamine (P less than 0.01), but not by prazosin or phentolamine + propranolol; no treatment affected the total number of couplets, ventricular tachycardia episodes and ventricular ectopic complexes, or the incidence of ventricular tachycardia and ventricular fibrillation. During coronary reperfusion, arrhythmias did not differ in control and treated groups. Thus, selective alpha 1-(prazosin), nonselective alpha 1- and alpha 2-(phentolamine), and combined alpha- and beta-blockade (phentolamine + propranolol) failed to attenuate complex arrhythmias induced by acute myocardial ischemia and reperfusion. Alpha-adrenergic mechanisms appear unimportant in the genesis of these arrhythmias in the canine model.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000150:complications*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000150:complications; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000097:blood / Q000494:pharmacology; D011433:Propranolol / Q000097:blood / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D002245:Carbon Dioxide; D011433:Propranolol; D011224:Prazosin; D010646:Phentolamine