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CLINICAL STUDIES

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

^a Clinic for Internal Medicine/Cardiology, University of Leipzig, Herzzentrum GmbH, Leipzig, Germany

Manuscript received July 9, 1998; revised manuscript received October 14, 1998, accepted November 18, 1998.

Reprint requests and correspondence: Dr. Volker Adams, Universität Leipzig, Herzzentrum GmbH, Klinik für Innere Medizin/Kardiologie, Russenstrasse 19, D-04289 Leipzig, Germany
adav{at}server3.medizin.uni-leipzig.de

OBJECTIVES

The purpose of the study was to investigate if apoptosis occurs in skeletal muscle myocytes and its relation to exercise intolerance in patients with chronic heart failure (CHF).

BACKGROUND

Intrinsic abnormalities of skeletal muscle frequently limit exercise tolerance in CHF patients. Recently, apoptosis has been detected in cardiac myocytes of patients with CHF, suggesting that apoptosis may contribute to the reduced contractile force. The presence and regulation of apoptosis 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 healthy control subjects were analyzed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling for the presence of apoptosis, and by immunohistochemistry and videodensitometrical quantification for inducible nitric oxide synthase (iNOS) and Bcl-2 expression. Maximal oxygen consumption (VO₂max) 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 VO₂max (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 expression (1.0 ± 0.3 vs. 1.4 ± 0.4% Bcl-2–positive tissue area; p = 0.03) as compared with patients with apoptosis-negative biopsies.

CONCLUSIONS

These results indicate that apoptosis is frequently found in skeletal muscle obtained from CHF patients, which is associated with significant impairment of functional work capacity. In skeletal muscle of these patients, iNOS and Bcl-2 are possibly involved in the regulation of apoptosis.

Abbreviations and Acronyms   CHF = chronic heart failure   iNOS = inducible nitric oxide synthase   NO = nitric oxide   RT = room temperature   TdT = terminal deoxynucleotidyl transferase   TUNEL = terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling

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