Autonomic control of ventricular tachycardia: direct effects of beta-adrenergic blockade in 24 hour old canine myocardial infarction.
The purpose of this study was to determine whether alpha- or beta-adrenergic influences directly modulate the rate of spontaneous ventricular tachycardia occurring 24 hours after left anterior descending coronary artery occlusion. Chloralose-anesthetized, open chest dogs (n = 41) with ventricular tachycardia were studied. The left anterior descending artery was cannulated distally. Neither intracoronary saline solution nor phenylephrine (0.3 to 12 micrograms) changed the rate of ventricular tachycardia; however, isoproterenol (0.01 to 10 micrograms) produced dose-dependent increases in the rate. In six dogs, metoprolol, 5 mg given intravenously, slowed ventricular tachycardia from 174 +/- 10 (mean +/- SE) to 140 +/- 17 beats/min (p less than 0.05). This was accompanied by decreases in mean arterial pressure from 106 +/- 7 to 95 +/- 8 mm Hg, cardiac output from 2.6 +/- 0.3 to 1.6 +/- 0.3 liters/min and prolongation of atrioventricular conduction from 134 +/- 10 to 189 +/- 29 ms (all p less than 0.05) during atrial pacing at a cycle length of 300 ms. In 10 dogs, metoprolol (0.5 mg) given intracoronary, a dose that shifted the isoproterenol dose-response curve to the right, slowed ventricular tachycardia from 174 +/- 7.2 to 140 +/- 9.7 beats/min (p less than 0.05) without hemodynamic changes. Additional metoprolol (4.5 mg) given intravenously produced hemodynamic alterations, but ventricular tachycardia did not slow further. Therefore, beta- but not alpha-adrenergic influences control the rate of ventricular tachycardia occurring 24 hours after left anterior descending coronary artery occlusion. Furthermore, beta-adrenergic blockade slows ventricular tachycardia solely by a direct electrophysiologic effect on the tachycardia foci and not indirectly as a result of hemodynamic effects.
D000818:Animals; D003331:Coronary Vessels; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007269:Injections, Intra-Arterial; D007545:Isoproterenol / Q000627:therapeutic use; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000150:complications*; D010656:Phenylephrine / Q000494:pharmacology* / Q000627:therapeutic use; D013610:Tachycardia / Q000209:etiology / Q000517:prevention & control*
D010656:Phenylephrine; D008790:Metoprolol; D007545:Isoproterenol