Effects of endurance training on mitochondrial ultrastructure and fiber type distribution in skeletal muscle of patients with stable chronic heart failure.
OBJECTIVE
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 perfusion.


BACKGROUND
Recent studies in patients with CHF have suggested that intrinsic abnormalities in skeletal muscle can contribute to the development of early lactic acidosis and fatigue during exercise. METHODS; Patients were prospectively randomized to either a training group (n = 9; mean [+/- SD] left ventricular ejection fraction [LVEF] 26 +/- 10) participating in an ambulatory training program or to a physically inactive control group (n = 9; LVEF 28 +/- 10%). At baseline and after 6 months, patients underwent symptom-limited bicycle exercise testing with measurement of central and peripheral hemodynamic variables as well as percutaneous needle biopsies of the vastus lateralis muscle. The mitochondrial ultrastructure of skeletal muscle was analyzed by ultrastructural morphometry; cytochrome c oxidase activity was visualized by histochemistry and subsequently quantitated by morphometry. The fiber type distribution was determined by adenosine triphosphatase staining.


RESULTS
After 6 months of exercise training there was a significant increase of 41% in the surface density of cytochrome c oxidase-positive 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. control). In contrast, the total number of cytochrome c oxidase-positive mitochondria remained essentially unchanged. Exercise-induced improvement in peak oxygen uptake was closely linked to changes in SVMOcox+ (p < 0.01, r = 0.66). After exercise training, changes in submaximal femoral venous lactate levels were not related to changes in submaximal leg 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 changes 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).


CONCLUSIONS
Patients with CHF who engage in regular physical exercise show enhanced oxidative enzyme activity in the working skeletal muscle and a concomitant reshift to type I fibers. These exercise-induced changes in oxidative capacity appear to be unrelated to changes in peripheral perfusion.
Hambrecht
R
R
Herzzentrum der Universitat Leipzig, Abteilung Kardiologie, Germany.
Fiehn
E
E
Yu
J
J
Niebauer
J
J
Weigl
C
C
Hilbrich
L
L
Adams
V
V
Riede
U
U
Schuler
G
G
D003576:Electron Transport Complex IV / Q000378:metabolism; D005080:Exercise Test; D005081:Exercise Therapy; D006333:Heart Failure / Q000473:pathology* / Q000534:rehabilitation; D006801:Humans; D007866:Leg / Q000098:blood supply; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000648:ultrastructure*; D018485:Muscle Fibers, Skeletal; D009206:Myocardium / Q000201:enzymology; D010101:Oxygen Consumption; D011446:Prospective Studies; D011659:Pulmonary Gas Exchange; D012039:Regional Blood Flow
D003576:Electron Transport Complex IV