Apoptosis in skeletal myocytes of patients with chronic heart failure is associated with exercise intolerance

OBJECTIVES The purpose of the study was to investigate if apoptosis occurs in skeletal muscle myocytes and its relation to exercise intolerance in pat ients with chronic heart failure (CHF). BACKGROUND Intrinsic abnormalities of skeletal muscle frequently limit exer cise tolerance in CHF patients. Recently, apoptosis has been detected in ca rdiac myocytes of patients with CHF, suggesting that apoptosis may contribu te to the reduced contractile force. The presence and regulation of apoptos is in skeletal myocytes of patients with CHF remains to be defined. METHODS Skeletal muscle biopsies (m. vastus lateralis) of 34 CHF patients ( New York Heart Association functional class II-III) and eight age-matched h ealthy control subjects were analyzed by terminal deoxynucleotidyl transfer ase-mediated deoxyuridine triphosphate nick end-labeling for the presence o f apoptosis, and by immunohistochemistry and videodensitometrical quantific ation for inducible nitric oxide synthase (iNOS) and Bcl-2 expression. Maxi mal oxygen consumption (VO(2)max) was determined by ergospirometry. RESULTS Apoptosis was detected in 16/34 (47%) patients with CHF and in none of the healthy subjects. Patients with apoptosis-positive skeletal muscle myocytes exhibited a significantly lower VO(2)max (12.0 +/- 3.7 vs: 18.2 +/ - 4.4 ml/kg/min; p = 0.0005), a higher iNOS expression (6.8 +/- 3.6 vs. 3.7 +/- 2.6% iNOS-positive stained tissue area; p = 0.015) and a lower Bcl-2 e xpression (1.0 +/- 0.3 vs. 1.4 +/- 0.4% Bcl-2-positive tissue area; p = 0.0 3) as compared with patients with apoptosis-negative biopsies. CONCLUSIONS These results indicate that apoptosis is frequently found in sk eletal muscle obtained from CHF patients, which is associated with signific ant impairment of functional work capacity. In skeletal muscle of these pat ients, iNOS and Bcl-2 are possibly involved in the regulation of apoptosis. (J Am Coil Cardiol 1999;33:959-65) (C) 1999 by the American College of Car diology.