EFFECTS OF ENDURANCE TRAINING ON MITOCHONDRIAL ULTRASTRUCTURE AND FIBER-TYPE DISTRIBUTION IN SKELETAL-MUSCLE OF PATIENTS WITH STABLE CHRONIC HEART-FAILURE

Objectives. The present study was designed to evaluate the effects of an ambulatory training program in patients with chronic heart failure (CHF) on the ultrastructural morphology of mitochondria and fiber type distribution of skeletal muscle and its relation to peripheral perfus ion. Background. Recent studies in patients with CHF have suggested th at intrinsic abnormalities in skeletal muscle can contribute to the de velopment of early lactic acidosis and fatigue during exercise. Method s. Patients mere prospectively randomized to either a training group ( n = 9; mean [+/-SD] left ventricular ejection fraction [LVEF] 26 +/- 1 0%) participating in an ambulatory training program or to a physically inactive control group (n = 9; LVEF 28 +/- 10%). At baseline and afte r 6 months, patients underwent symptom-limited bicycle exercise testin g with measurement of central and peripheral hemodynamic variables as well as percutaneous needle biopsies of the vastus lateralis muscle. T he mitochondrial ultrastructure of skeletal muscle was analyzed by ult rastructural morphometry; cytochrome c oxidase activity was visualized by histochemistry and subsequently quantitated by morphometry. The fi ber type distribution was determined by adenosine triphosphatase stain ing.Results. After 6 months of exercise training there was a significa nt increase of 41% in the surface density of cytochrome c oxidase-posi tive mitochondria (SVMOcox+) (p < 0.05 vs. control) and of 43% in the surface density of mitochondrial cristae (SVMC) (p < 0.05 vs. control) . Furthermore, exercise training induced a 92% increase in the surface density of the mitochondrial inner border membrane (p < 0.05 vs. cont rol). In contrast, the total number of cytochrome c oxidase-positive m itochondria remained essentially unchanged. Exercise-induced improveme nt in peak oxygen uptake was closely linked to changes in SVMOcox+ (p < 0.01, r = 0.66). After exercise training, changes in submaximal femo ral venous lactate levels mere not related to changes in submaximal le g blood flow (r = -0.4), but were inversely related to changes in the volume density of mitochondria (p = 0.01; r = -0.6) as well as to chan ges in SVMC (p < 0.05; r = -0.5). After exercise training there was a ''reshift'' from type II to type I fibers (p < 0.05 vs. control). Conc lusions. Patients with CHF who engage in regular physical exercise sho w enhanced oxidative enzyme activity in the working skeletal muscle an d a concomitant reshift to type I fibers. These exercise-induced chang es in oxidative capacity appear to be unrelated to changes in peripher al perfusion. (C)1997 by the American College of Cardiology.