The role of enhanced vagal activity on ischemic ventricular tachycardia: pharmacologic basis of inefficiency.
The effects of pharmacologic modulation of vagal activity on ischemic ventricular tachycardia were evaluated in 21 conscious dogs after permanent left anterior descending coronary artery (LAD) occlusion. Studies were done on spontaneous ventricular tachycardia (cycle length 383 +/- 100 msec, n = 21), 24 to 72 hours after LAD occlusion, and on inducible sustained monomorphic ventricular tachycardia (cycle length 251 +/- 30 msec, n = 6), 4 to 7 days after LAD occlusion. Edrophonium (1 mg/kg intravenously), a cholinesterase inhibitor, and methacholine (0.1 to 1 mg intravenously), a muscarinic agonist, had no significant effect on the rate or QRS morphology of either type of tachycardia, despite severe slowing of the sinoatrial rate. Similarly, atropine (up to 60 micrograms/kg intravenously) had no effect on the rate and QRS morphology of either type of tachycardia. In an attempt to enhance myocardial drug delivery to the ischemic and infarcted left ventricle, edrophonium (1 mg/kg) and methacholine (0.1 to 0.2 mg) were injected retrogradely through the great cardiac vein. This did not impart any significant therapeutic advantage over the systemic intravenous route. Sympathetic beta blockade did not affect the therapeutic outcome (n = 5) with either edrophonium or methacholine. It is concluded that direct or indirect enhancement of cardiac vagal activity has no effect on ischemic ventricular tachycardia in this model of subacute myocardial infarction. The lack of efficacy appears to be independent of myocardial drug delivery to ischemic ventricular site(s) and background sympathetic activity. Such a lack of efficacy may be caused by ischemia-mediated degeneration of vagal nerve terminals, by altered responsiveness of muscarinic receptors at infarcted arrhythmogenic myocardial sites, or both.
Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
M
M
Meesmann
H S
HS
Karagueuzian
T
T
Ino
M F
MF
McGrath
W J
WJ
Mandel
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002304:Cardiac Pacing, Artificial; D003326:Coronary Circulation; D003327:Coronary Disease / Q000150:complications*; D004285:Dogs; D004491:Edrophonium / Q000494:pharmacology; D004562:Electrocardiography; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009203:Myocardial Infarction / Q000473:pathology; D013610:Tachycardia / Q000209:etiology* / Q000503:physiopathology; D014630:Vagus Nerve / Q000503:physiopathology*
D000319:Adrenergic beta-Antagonists; D016210:Methacholine Chloride; D004491:Edrophonium; D001285:Atropine