Attenuated fatigue in slow twitch skeletal muscle during isotonic exercise in rats with chronic heart failure.

Morten Munkvik,Per Kristian Lunde,Ole M Sejersted,Jan Magnus Aronsen,Jon Arne Kro Birkeland,Ivar Sjaastad,Alejandro Lucia

doi:10.1371/journal.pone.0022695

Morten Munkvik, Per Kristian Lunde + Show 5 more

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https://doi.org/10.1371/journal.pone.0022695

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Abstract

During isometric contractions, slow twitch soleus muscles (SOL) from rats with chronic heart failure (chf) are more fatigable than those of sham animals. However, a muscle normally shortens during activity and fatigue development is highly task dependent. Therefore, we examined the development of skeletal muscle fatigue during shortening (isotonic) contractions in chf and sham-operated rats. Six weeks following coronary artery ligation, infarcted animals were classified as failing (chf) if left ventricle end diastolic pressure was >15mmHg. During isoflurane anaesthesia, SOL with intact blood supply was stimulated (1s on 1s off) at 30Hz for 15 min and allowed to shorten isotonically against a constant afterload. Muscle temperature was maintained at 37°C. In resting muscle, maximum isometric force (Fmax) and the concentrations of ATP and CrP were not different in the two groups. During stimulation, Fmax and the concentrations declined in parallel sham and chf. Fatigue, which was evident as reduced shortening during stimulation, was also not different in the two groups. The isometric force decline was fitted to a bi-exponential decay equation. Both time constants increased transiently and returned to initial values after approximately 200 s of the fatigue protocol. This resulted in a transient rise in baseline tension between stimulations, although this effect which was less prominent in chf than sham. Myosin light chain 2s phosphorylation declined in both groups after 100 s of isotonic contractions, and remained at this level throughout 15 min of stimulation. In spite of higher energy demand during isotonic than isometric contractions, both shortening capacity and rate of isometric force decline were as well or better preserved in fatigued SOL from chf rats than in sham. This observation is in striking contrast to previous reports which have employed isometric contractions to induce fatigue.

Highlights

Limited exercise capacity is a hallmark of chronic heart failure
Contrary to the hypothesis that shortening contractions would reveal an even more attenuated muscle function than isometric contractions, we found that skeletal muscle from heart failure rats tolerated shortening contractions very well, even better that the sham animals
Animal characteristics In comparison with sham, chf animals exhibited elevated end diastolic pressure (EDP), lower systolic blood pressure, and dilated left ventricular dimensions during diastole (163% compared to sham, Table 2)

Summary

Introduction

Limited exercise capacity is a hallmark of chronic heart failure (chf). Central hemodynamic deterioration with low cardiac output, reduced perfusion of working skeletal muscle and low anaerobic threshold likely contribute to the fatigue development in these patients. It has become clear that the muscle itself demonstrates pathological features, independent of cardiac function [3]. During heart failure skeletal muscle function is found to be altered both in experimental models and in patients. One main experimental finding is reduced exercise tolerance to isometric contractions [4]. Increased fatigue in this setting seems not to be due to reduced muscle perfusion [5]

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