Repolarization abnormalities, arrhythmia and sudden death in canine tachycardia-induced cardiomyopathy.
OBJECTIVE
This study sought to determine whether the canine model of tachycardia-induced heart failure (HF) is an effective model for sudden cardiac death (SCD) in HF.


BACKGROUND
Such a well established HF model that also exhibits arrhythmias and SCD, along with repolarization abnormalities that could trigger them, may facilitate the study of SCD in HF, which still eludes effective treatment.


METHODS
Twenty-five dogs were VVI-paced at 250 beats/min for 3 to 5 weeks. Electrocardiograms were obtained, and left ventricular endocardial monophasic action potentials (MAPs) were recorded at six sites at baseline and after HF. Weekly Holter recordings were made with pacing suspended for 24 h.


RESULTS
Six animals (24%) died suddenly, one with Holter-documented polymorphic ventricular tachycardia (VT). Holter recordings revealed an increased incidence of VT as HF progressed. Repolarization was significantly (p < 0.05) prolonged, as indexed by a corrected QT interval (mean [+/-SD] 311 +/- 25 to 338 +/- 25 ms) and MAP duration measured at 90% repolarization (MAPD90) (181 +/- 19 to 209 +/- 28 ms), and spatial MAPD90 dispersion rose by 40%. We further tested whether CsCl inhibition of repolarizing K+ currents, which are reportedly downregulated in HF, might preferentially prolong the MAPD90 in HF. With 1 mEq/kg body weight of CsCl, MAPD90 rose by 86 +/- 100 ms in dogs with HF versus only 28 +/- 16 ms in control animals (p = 0.002). Similar disparities in CsCl sensitivity were observed in myocytes isolated from normal and failing hearts.


CONCLUSIONS
Tachycardia-induced HF exhibits malignant arrhythmia and SCD, along with prolonged, heterogeneous repolarization and heightened sensitivity to CsCl at chamber and cellular levels. Thus, it appears to be a useful model for studying mechanisms and therapy of SCD in HF.
Pak
P H
PH
Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. peterpak@welchlink.welch.jhu.edu
Nuss
H B
HB
Tunin
R S
RS
Kääb
S
S
Tomaselli
G F
GF
Marban
E
E
Kass
D A
DA
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000209:etiology; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D004285:Dogs; D004562:Electrocardiography; D004594:Electrophysiology; D005260:Female; D006333:Heart Failure; D008297:Male; D013610:Tachycardia / Q000150:complications*
D002712:Chlorides; D002586:Cesium; C028019:cesium chloride