Hypertrophy causes delayed conduction in human and Guinea pig myocardium: Accentuation during ischaemic perfusion

Abstract

Objective: The aim was to investigate why cardiac hypertrophy causes increased vulnerability to arrhythmias during myocardial ischaemia. Methods: The electrophysiological basis for this increased vulnerability was studied in isolated perfused Guinea pig hearts obtained 50 and 150 d after aortic constriction, and in sham operated controls. Cellular electrophysiology, conduction, and refractory periods were examined during control perfusion and during low flow (coronary flow reduced to 10% of control) and zero flow ischaemia. ECGs in patients with left ventricular hypertrophy and in controls matched for age and heart rate were also studied. Results: Aortic constriction increased heart weight:body weight ratio by 33% at 50 d and by 69% at 150 d. Action potentials were unchanged in hypertrophied hearts. Significant conduction delay occurred in 150 d hypertrophied hearts [conduction time index 23(SEM 4) ms v 18(3) ms, p<0.001; QRS width 40(1) ms v 35(1) ms, p<0.01], but not in 50 d hypertrophied hearts. Conduction delay was also present in humans with left ventricular hypertrophy [QRS width 96(13) ms v 87(8) ms, p<0.01]. Although the QTc interval was increased in humans, at 422(23) ms v 411(17) ms in controls, p<0.05, this could be explained by the increased QRS duration. During ischaemia, ventricular arrhythmias tended to occur earlier in hypertrophied hearts. Hypertrophy was also associated with a greater increase in conduction delay. Ischaemia reduced action potential duration and refractory periods; the reduction in action potential duration was attenuated by hypertrophy (p<0.01), although the reverse was apparent during low flow ischaemia at 50 d. Conclusions: Delayed conduction is an important feature of severe cardiac hypertrophy in Guinea pigs and man. Hypertrophy is associated with accentuated conduction delay and altered repolarisation during ischaemia.Cardiovascular Research 1994;28:47-54.