Enhanced Ca(2+) release and Na/Ca exchange activity in hypertrophied canine ventricular myocytes: potential link between contractile adaptation and arrhythmogenesis

Ventricular arrhythmias are a major cause of sudden death in patients with heart failure and hypertrophy. The dog with chronic complete atrioventricular block (CAVB) has biventricular hypertrophy and ventricular arrhythmias and is a useful model to study underlying cellular mechanisms. We investigat...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 2000-10, Vol.102 (17), p.2137-2144
Main Authors: Sipido, K R, Volders, P G, de Groot, S H, Verdonck, F, Van de Werf, F, Wellens, H J, Vos, M A
Format: Article
Language:English
Subjects:
Adaptation, Biological
Animals
Arrhythmias, Cardiac - etiology
Biological Transport
Calcium - metabolism
Calcium Channels, L-Type - metabolism
Cardiomegaly - metabolism
Cardiomegaly - physiopathology
Disease Models, Animal
Dogs
Heart Block - physiopathology
Heart Ventricles - cytology
Heart Ventricles - metabolism
Heart Ventricles - physiopathology
Membrane Potentials
Myocardial Contraction - physiology
Sarcoplasmic Reticulum - metabolism
Sodium-Calcium Exchanger - metabolism
Up-Regulation
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Summary:Ventricular arrhythmias are a major cause of sudden death in patients with heart failure and hypertrophy. The dog with chronic complete atrioventricular block (CAVB) has biventricular hypertrophy and ventricular arrhythmias and is a useful model to study underlying cellular mechanisms. We investigated whether changes in Ca(2+) homeostasis are part of the contractile adaptation to CAVB and might contribute to arrhythmogenesis. In enzymatically isolated myocytes, cell shortening, Ca(2+) release from the sarcoplasmic reticulum (SR), and SR Ca(2+) content were enhanced at low stimulation frequencies. Ca(2+) influx through L-type Ca(2+) channels was unchanged, but Ca(2+) influx via the Na/Ca exchanger was increased and contributed to Ca(2+) loading of the SR. Inward Na/Ca exchange currents were also larger. Changes in Ca(2+) fluxes were less pronounced in the right versus left ventricle. Enhanced Na/Ca exchange activity may improve contractile adaptation to CAVB but at the same time facilitate arrhythmias by (1) increasing the propensity to Ca(2+) overload, (2) providing more inward current leading to (nonhomogeneous) action potential prolongation, and (3) enhancing (arrhythmogenic) currents during spontaneous Ca(2+) release.
ISSN:0009-7322
1524-4539
DOI:10.1161/01.CIR.102.17.2137