Mechanism of prevention of sudden death by nadolol: differential actions on arrhythmia triggers and substrate after myocardial infarction in the dog.
Electrocardiographic monitoring and provocative ventricular pacing were used to evaluate control and nadolol treatment groups 6 to 24 hours after left anterior descending coronary artery ligation in the dog. During the 6 to 24 hour period, the control group (n = 20) developed ventricular triplets at rates exceeding 270/min. Seven dogs spontaneously developed sustained monomorphic ventricular tachycardia (421 +/- 12 beats/min) at 13 +/- 2 hours. Sustained monomorphic ventricular tachycardia was present for 38 +/- 8 seconds before ventricular fibrillation developed. One dog developed recurrent monomorphic ventricular tachycardia, with six episodes lasting from 8 to 72 seconds (375 to 425 beats/min). At 24 hours, ventricular pacing produced sustained monomorphic ventricular tachycardia (378 +/- 12 beats/min) in 9 of 13 surviving animals. Nadolol administration 6 hours after coronary artery ligation (n = 19) lowered both the rate (241 +/- 8 versus 328 +/- 8 beats/min; p = 0.001) and the incidence (8 +/- 6 versus 198 +/- 61 per hour; p = 0.004) of rapid ventricular triplets and prevented sudden arrhythmic death (0%; p = 0.005). Nadolol failed to prevent sustained monomorphic ventricular tachycardia (88%; 365 +/- 12 beats/min) produced by ventricular pacing. The data suggest that nadolol prevents spontaneous sustained monomorphic ventricular tachycardia by selectively suppressing the arrhythmia trigger (rapid ventricular triplets) without altering the underlying arrhythmia substrate.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology / Q000517:prevention & control*; D001696:Biomechanical Phenomena; D003645:Death, Sudden / Q000209:etiology*; D004285:Dogs; D004562:Electrocardiography; D004594:Electrophysiology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D009248:Nadolol / Q000627:therapeutic use*
D009248:Nadolol