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This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/H1069    most recent 01009.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mørk, H. K. Articles by Louch, W. E. Search for Related Content PubMed PubMed Citation Articles by Mørk, H. K. Articles by Louch, W. E.

Slowing of cardiomyocyte Ca²⁺ release and contraction during heart failure progression in postinfarction mice

¹Institute for Experimental Medical Research, Ullevaal University Hospital, Oslo; ²Centre for Heart Failure Research, Faculty of Medicine, University of Oslo; and ³Department of Cardiology, Ullevaal University Hospital, Oslo, Norway

Submitted 17 September 2008 ; accepted in final form 30 January 2009

Deterioration of cardiac contractility during congestive heart failure (CHF) is believed to involve decreased function of individual cardiomyocytes and may include reductions in contraction magnitude and/or kinetics. We examined the progression of in vivo and in vitro alterations in contractile function in CHF mice and investigated underlying alterations in Ca²⁺ homeostasis. Following induction of myocardial infarction (MI), mice with CHF were examined at early (1 wk post-MI) and chronic (10 wk post-MI) stages of disease development. Sham-operated mice served as controls. Global and local left ventricle function were assessed by echocardiography in sedated animals (2% isoflurane). Excitation-contraction coupling was examined in cardiomyocytes isolated from the viable septum. CHF progression between 1 and 10 wk post-MI resulted in increased mortality, development of hypertrophy, and deterioration of global left ventricular function. Local function in the noninfarcted myocardium also declined, as posterior wall shortening velocity was reduced in chronic CHF (1.2 ± 0.1 vs. 1.9 ± 0.2 cm/s in sham). Parallel alterations occurred in isolated cardiomyocytes since contraction and Ca²⁺ transient time to peak values were prolonged in chronic CHF (115 ± 6 and 158 ± 11% sham values, respectively). Surprisingly, contraction and Ca²⁺ transient magnitudes in CHF were larger than sham values at both time points, resulting from increased sarcoplasmic reticulum Ca²⁺ content and greater Ca²⁺ influx via L-type channels. We conclude that, in mice with CHF following myocardial infarction, declining myocardial function involves slowing of cardiomyocyte contraction without reduction in contraction magnitude. Corresponding alterations in Ca²⁺ transients suggest that slowing of Ca²⁺ release is a critical mediator of CHF progression.

excitation-contraction coupling; cardiac contraction; calcium; cardiomyocytes