Affiliation:
1. From the Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands, and the Laboratory of Experimental Cardiology, University of Leuven, Belgium (K.R.S.).
Abstract
Background
—In the dog with chronic complete atrioventricular block (AVB), torsade de pointes arrhythmias (TdP) can be induced reproducibly by class III antiarrhythmic agents. In vivo studies reveal important electrophysiological alterations of the heart at 5 weeks of AVB, resulting in increased proarrhythmia. Autopsy studies indicate the presence of biventricular hypertrophy. In this study, the cellular basis of proarrhythmia and hypertrophy in chronic AVB was investigated.
Methods and Results
—From chronic-AVB dogs with increased heart weights and TdP, left midmyocardial and right ventricular myocytes were isolated by enzymatic dispersion. These myocytes were significantly larger than sinus rhythm (SR) controls. In chronic AVB, the action potential spike-and-dome configuration was preserved. However, the action potential duration (APD) at 95% and 50% of repolarization of the left midmyocardium was significantly larger in chronic AVB than in SR, with little change in the right ventricle, causing enhanced interventricular dispersion of repolarization at slow pacing rates. Treatment with the class III agent almokalant increased the APD to a much larger extent in chronic-AVB than in SR myocytes and resulted in a higher incidence of early afterdepolarizations (EADs). EADs had their takeoff potential between −35 and 0 mV. There was no evidence that spontaneous sarcoplasmic reticulum Ca
2+
release underlies these EADs.
Conclusions
—In the dog, chronic AVB leads to hypertrophy of both right and left ventricular myocytes. The repolarization abnormalities predisposing for class III–dependent TdP in vivo are the results of cellular electrophysiological remodeling.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
160 articles.
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