Canine left ventricular hypertrophy predisposes to ventricular tachycardia induction by phase 2 early afterdepolarizations after administration of BAY K 8644.
OBJECTIVE
The purpose of this study was to test the hypothesis that the longer duration of ventricular action potentials in hypertrophied hearts predisposes to the development of early after-depolarizations and triggered ventricular tachyarrhythmias.


BACKGROUND
For unknown reasons, the incidence of sudden death is greater in patients with myocardial hypertrophy.


METHODS
We measured left ventricular monophasic action potentials in normal dogs and dogs with left ventricular hypertrophy before and after administration of the calcium agonist BAY K 8644 and the potassium channel blocker cesium.


RESULTS
We demonstrated longer action potential durations in dogs with than in those without left ventricular hypertrophy. Also, BAY K 8644 produced phase 2 early afterdepolarizations and ventricular tachyarrhythmias more frequently in the dogs with than in those without left ventricular hypertrophy. Phenylephrine, an alpha agonist, further increased the action potential duration in hypertrophied hearts and the propensity to develop early afterdepolarizations and ventricular tachyarrhythmia after administration of BAY K 8644. Control and hypertrophied hearts developed early afterdepolarizations and ventricular tachyarrhythmia equally when exposed to cesium.


CONCLUSIONS
Although in vitro studies have shown that fibers of hypertrophied ventricular myocardium can develop triggered activity as a result of both early and late afterdepolarizations, the present study is the first to show in vivo that the hypertrophied ventricular myocardium compared with the normal ventricle is predisposed to develop phase 2 early afterdepolarizations that appear to trigger ventricular tachyarrhythmia. It is possible that such a mechanism contributes to the development of ventricular tachyarrhythmia and sudden cardiac death in patients with left ventricular hypertrophy. If this is shown to be true, specific pharmacologic interventions can be suggested.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000008:administration & dosage / Q000009:adverse effects*; D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D015984:Causality; D002586:Cesium / Q000009:adverse effects; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology; D004195:Disease Models, Animal; D004285:Dogs; D005069:Evaluation Studies as Topic; D006439:Hemodynamics / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D015994:Incidence; D009929:Organ Size / Q000187:drug effects; D010656:Phenylephrine / Q000009:adverse effects; D015995:Prevalence; D017180:Tachycardia, Ventricular / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D013997:Time Factors
D002586:Cesium; D010656:Phenylephrine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester