Studies on apoptosis and fibrosis in skeletal musculature: a comparison of heart failure patients with and without cardiac cachexia.
Apoptosis has been found in skeletal muscles of patients with chronic heart failure (CHF) and has been associated with exercise intolerance. In CHF, cachexia is characterized by neurohormonal activation and muscle wasting. Neurohormonal activation can lead to cell death and fibrosis. The purpose of the study was to determine the severity of apoptosis and fibrosis in skeletal muscles of patients with CHF and cachexia and its relationship to exercise intolerance in these patients. Skeletal muscle biopsies of 21 patients with CHF (eight with cachexia) and four healthy controls of similar age have been studied by in situ end labeling (ISEL) for apoptosis and by the Picrosirius Red technique for collagen. Apoptosis in skeletal muscles was detected by ISEL in 52% of the patients with CHF (11 out of 21) and in none of the controls. CHF patients with apoptosis-positive skeletal muscles had impaired exercise tolerance (peak oxygen consumption 11.4+/-5.7 vs. 16.91+/-6.6, P=0.029). Increased collagen was detected by Picrosirius Red in eight out of 21 patients with CHF and in none of the controls. Increased collagen (fibrosis) was detected in six out of eight patients with cachexia and in two out of 13 patients without cachexia (P=0.01). Peak oxygen consumption and apoptosis were similar in cachectic and non-cachectic patients. Thus, the skeletal musculature of patients with cardiac cachexia is characterised by the presence of fibrosis. Apoptosis was not found to be more frequent in cachectic CHF patients. Our data support the hypothesis that cachexia contributes by a different mechanism to skeletal muscle myopathy of CHF patients and different mechanisms are implicated in deterioration of exercise tolerance and progression to cardiac cachexia.
Filippatos
Gerasimos S
GS
Second Department of Cardiology, Evangelismos General Hospital, 28 Doukissis Plakentias street, 115 23, Athens, Greece. geros@compulink.gr
Kanatselos
Christos
C
Manolatos
Dimitris D
DD
Vougas
Bill
B
Sideris
Anthony
A
Kardara
Dimitra
D
Anker
Stefan D
SD
Kardaras
Fotios
F
Uhal
Bruce
B
D000368:Aged; D017209:Apoptosis; D002100:Cachexia / Q000150:complications / Q000473:pathology*; D002908:Chronic Disease; D017079:Exercise Tolerance; D005260:Female; D005355:Fibrosis / Q000473:pathology*; D006333:Heart Failure / Q000150:complications / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology*; D012720:Severity of Illness Index