Unloaded rat hearts in vivo express a hypertrophic phenotype of cardiac repolarization

Journal of Molecular and Cellular Cardiology
Alexander Peter SchwoererH Ehmke

Abstract

Cardiac unloading with left ventricular assist devices is increasingly used to treat patients with severe heart failure. Unloading has been shown to improve systolic and diastolic function, but its impact on the repolarization of left ventricular myocytes is not known. Unloaded hearts exhibit similar patterns of gene expression as hearts subjected to an increased hemodynamic load. We therefore hypothesized that cardiac unloading also replicates the alterations in action potential and underlying repolarizing ionic currents found in pressure-overload induced cardiac hypertrophy. Left ventricular unloading was induced by heterotopic heart transplantation in syngenic male Lewis rats. Action potentials and underlying K+ and Ca2+ currents were investigated using whole-cell patch-clamp technique. Real-time RT-PCR was used to quantify mRNA expression of Kv4.2, Kv4.3, and KChIP2. Unloading markedly prolonged cardiac action potentials and suppressed the amplitude of several repolarizing K+ currents, in particular of the transient outward K+ current I(to), in both, epicardial and endocardial myocytes. The reduction of I(to) was associated with significantly lower levels of Kv4.2 and Kv4.3 mRNAs in epicardial myocytes, and of KChIP2 mRNA i...Continue Reading

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Citations

Oct 14, 2008·Journal of Molecular and Cellular Cardiology·Alexander P SchwoererAli El-Armouche
Mar 22, 2014·Journal of Molecular and Cellular Cardiology·Kedryn K BaskinHeinrich Taegtmeyer
Jun 9, 2012·Journal of the American College of Cardiology·Maxim HardziyenkaHanno L Tan
Jun 9, 2012·Journal of the American College of Cardiology·Henry H Hsia, Francois Haddad
Sep 29, 2017·Cardiovascular Research·Robert Naeije, Roberto Badagliacca

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