Repolarization abnormalities and their arrhythmogenic consequences in porcine tachycardia-induced cardiomyopathy.

OBJECTIVES

Action potential prolongation related to the alteration of several membrane currents is constantly reported in heart failure (HF) but reports about its role in arrhythmogenesis are sparse. Our aim was to determine, by analogy with long QT syndromes, whether prolonged repolarization is associated with increased dispersion or linked to bradycardia-dependent ventricular arrhythmias in pacing-induced cardiomyopathy.

METHODS

QT intervals, action potentials and transmural activation-to-recovery intervals (ARIs) along with whole-cell delayed rectifier (I(K)) and transient outward (I(to1)) K+ currents were recorded in left ventricle from pigs with HF and controls. HF was obtained after 14 days of rapid pacing at 250 ms.

RESULTS

Repolarization was delayed as indexed by corrected QT intervals (13.7% increase, P<0.01) or ARIs (252+/-4 to 340+/-7 ms, P<0.01). ARIs were uniformly prolonged with disappearance of the transmural gradient, spatial dispersion of repolarization decreased by 50% (P<0.05). I(to1) density was reduced in HF from 1.35+/-0.1 to 0.57+/-0.04 pA/pF subepicardially, from 1.05+/-0.19 to 0.55+/-0.08 pA/pF midmyocardially and from 1.04+/-0.1 to 0.48+/-0.04 pA/pF subendocardially. I(K) density was significantly decreased in HF pigs vs. controls: subepicardially from 0.46+/-0.04 to 0.22+/-0.02 pA/pF; midmyocardially from 0.46+/-0.05 to 0.25+/-0.03 pA/pF; and subendocardially from 0.49+/-0.04 to 0.20+/-0.04 pA/pF following depolarization at +50 mV. Electrocardiogram (ECG) monitoring at the time of death did not disclose any polymorphic ventricular tachyarrhythmia.

CONCLUSION

Despite a profound alteration in K+ currents, repolarization is uniformly prolonged in this model with no proclivity to develop bradycardia-dependent arrhythmias.