The lack of slow force response in failing rat myocardium: role of stretch-induced modulation of Ca–TnC kinetics

Abstract

The slow force response (SFR) to stretch is an important adaptive mechanism of the heart. The SFR may result in ~ 20–30% extra force but it is substantially attenuated in heart failure. We investigated the relation of SFR magnitude with Ca²⁺ transient decay in healthy (CONT) and monocrotaline-treated rats with heart failure (MCT). Right ventricular trabeculae were stretched from 85 to 95% of optimal length and held stretched for 10 min at 30 °C and 1 Hz. Isometric twitches and Ca²⁺ transients were collected on 2, 4, 6, 8, 10 min after stretch. The changes in peak tension and Ca²⁺ transient decay characteristics during SFR were evaluated as a percentage of the value measured immediately after stretch. The amount of Ca²⁺ utilized by TnC was indirectly evaluated using the methods of Ca²⁺ transient "bump" and "difference curve." The muscles of CONT rats produced positive SFR and they showed prominent functional relation between SFR magnitude and the magnitude (amplitude, integral intensity) of Ca²⁺ transient "bump" and "difference curve." The myocardium of MCT rats showed negative SFR to stretch (force decreased in time) which was not correlated well with the characteristics of Ca²⁺ transient decay, evaluated by the methods of "bump" and "difference curve." We conclude that the intracellular mechanisms of Ca²⁺ balancing during stretch-induced slow adaptation of myocardial contractility are disrupted in failing rat myocardium. The potential significance of our findings is that the deficiency of slow force response in diseased myocardium may be diminished under augmented kinetics of Ca–TnC interaction.

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