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.).
Correspondence to Marc A. Vos, PhD, Department of Cardiology, Cardiovascular Research Institute Maastricht, University Hospital Maastricht, PO Box 5800, 6202 AZ, Maastricht, Netherlands. E-mail m.vos{at}cardio.azm.nl
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 Ca2+ 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.
© 1998 American Heart Association, Inc.
Basic Science Reports
Cellular Basis of Biventricular Hypertrophy and Arrhythmogenesis in Dogs With Chronic Complete Atrioventricular Block and Acquired Torsade de Pointes
Key Words: ventricles • arrhythmia • hypertrophy • action potentials • myocytes
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