CHANGES IN SKELETAL-MUSCLE BIOCHEMISTRY AND HISTOLOGY RELATIVE TO FIBER-TYPE IN RATS WITH HEART-FAILURE

One of the primary consequences of left ventricular dysfunction (LVD) after myocardial infarction is a decrement in exercise capacity. Sever al factors have been hypothesized to account for this decrement, inclu ding alterations in skeletal muscle metabolism and aerobic capacity. T he purpose of this study was to determine whether LVD-induced alterati ons in skeletal muscle enzyme activities, fiber composition, and fiber size are I) generalized in muscles or specific to muscles composed pr imarily of a given fiber type and 2) related to the severity of the LV D. Female Wistar rats were divided into three groups: sham-operated co ntrols (n = 13) and rats with moderate (n = 10) and severe (n = 7) LVD . LVD was surgically induced by ligating the left main coronary artery and resulted in elevations (P < 0.05) in left ventricular end-diastol ic pressure (sham, 5 +/- 1 mmHg; moderate LVD, 11 +/- I mmHg; severe L VD, 25 +/- 1 mmHg). Moderate LVD decreased the activities of phosphofr uctokinase (PFK) and citrate synthase in one muscle composed of type T IE fibers but did not modify fiber Composition or size of any muscle s tudied. However, severe LVD diminished the activity of enzymes involve d in terminal and beta-oxidation in muscles composed primarily of type I fibers, type IIA fibers, and type IIB fibers. In addition, severe L VD induced a reduction in the activity of PFK in type IIB muscle, a 10 % reduction in the percentage of type IID/X fibers, and a correspondin g increase in the portion of type TIE fibers. Atrophy of type I fibers , type IIA fibers, and/or type IIB fibers occurred in soleus and plant aris muscles of rats with severe LVD. These data indicate that rats wi th severe LVD after myocardial infarction exhibit 1) decrements in mit ochondrial enzyme activities independent of muscle fiber composition, 2) a reduction in PFK activity in type IIB muscle, 3) transformation o f type IID/X to type IIB fibers, and 4) atrophy of type I, IIA, and II B fibers.