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

Abstract

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.

Melusin protects from cardiac rupture and improves functional remodelling after myocardial infarction

“…Cardiomyocyte contractility undergoes important changes during post-MI remodelling with a phase of increased contractility followed by a late failing phase 14,15 . In line with previous studies, wild type cardiomyocytes isolated from hearts 3 days after MI showed faster contraction and relaxation than sham controls with larger Ca 2+ transients ( Figure 2F and G).…”

Changes in myofilament proteins, but not Ca2+ regulation, are associated with a high-fat diet-induced improvement in contractile function in heart failure

“…These are intriguing findings in that they contradict our in vivo LV contractility and in vitro cell shortening velocity results. However, conflicting reports of Ca 2ϩ transients and total SERCA and total/phosphorylated PLB have been reported in the same model of ligation-induced HF (1,9,10,14,28,50). While the increased Ca 2ϩ transients in the HFNC group might represent a compensatory response for the loss of viable myocardial tissue after infarction, it is contradictory to a decrease in myocyte shortening velocity.…”

Effects of levosimendan on calcium transient in norepinephrine-cultured neonatal rat ventricular myocytes

“…7 The amplitude and peak Ca 2+ of calcium transient decreased, the resting Ca 2+ increased, and the duration was prolonged in most models of heart failure, which induced the reduced myocardial contractility together. 8 The duration was also extended in our experiment.…”