Skeletal muscle oxidative capacity and exercise tolerance in rats with heart failure.

Abstract

Past research has shown the development of exercise intolerance after myocardial infarction (MI). The purpose of this study was to test the hypothesis that reductions in oxidative enzyme activity, in a variety of skeletal muscles, coincide with the development of exercise intolerance in a rat model of chronic heart failure (CHF) induced by MI. The animals were initially divided into two groups: sham-operated controls (Sham) and animals in which a MI was surgically induced. MI rats were then subdivided into two groups according to left ventricular end-diastolic pressure (LVEDP): <20 mm Hg [small MI (SMI)] and > 20 mm Hg [large MI (LMI)]. Exercise tolerance was measured by performing a progressive run to fatigue test (RTF). Citrate synthase (CS), 3-hydroxyacyl CoA dehydrogenase (HADH), and malate dehydrogenase (MDH) activities were measured in six hindlimb muscles. After approximately 6 wk of recovery, LVEDP differed among groups (P < 0.05): Sham (1 +/- 1 mm Hg, N = 7), SMI (7 +/- 2 mm Hg, N = 7), and LMI (30 +/- 2 mm Hg, N = 6). RTF was 20 +/- 1 min for Sham, 25 +/- 3 min for SMI, and 11 +/- 2 min for LMI (P < 0.05 for LMI vs Sham, SMI). Significant reductions in enzyme activity were found for all three enzymes in the red portion of the gastrocnemius muscles of LMI. However, no significant correlation was found between RTF and CS, HADH, or MDH in any muscle of the three groups of animals. The results of the present study demonstrate that severe left ventricular dysfunction is associated with reductions in exercise tolerance and modest decreases in oxidative enzyme activities in selected muscles. It does not appear, however, that the development of exercise intolerance in CHF and oxidative enzyme activities are mechanistically related to one another.