Structural and functional alterations of cardiac and skeletal muscle mitochondria in patients with congestive heart failure

GUZMAN MENTESANA, G; BAEZ, A; DOMINGUEZ, R; CORDOBA, R; LO PRESTI, M.S; RIVAROLA, W; PONS, P; FRETES, R; COMAY, D; PAGLINI, P

Bs As

Congreso; World Congress of Cardiology; 2008

World Heart Federation

The heart is highly dependent on mitochondria for the energy required for contractility and other metabolic activities. Mitochondria represent 30% of the total volume of cardiomyocytes and provide almost 90% of their energy. Defects in mitochondrial structure and function have been associated to dilated and hypertrophic cardiomyopathies. Here we studied the structure and function of cardiac and skeletal muscle mitochondria obtained from patients with congestive heart failure (CHF) type III –IV, to establish a possible correlation. Cardiac and skeletal muscle biopsies (left ventricle and pectoral muscle) were obtained from 10 patients during surgery; then were divided into: control (n:4): young patients with interauricular communication and normal ejection fraction; and patients with CHF type III-IV (n:6). Part of the samples were fixed and analyzed using a Zeiss electronic microscope. For functional activity mitochondria were isolated by subcelullar fractioning, determining the activity of the respiratory chain analyzing complex CIII by spectrophotometry. Protein concentrations were determined by the Bradford method. Statistical analysis were done by  ANOVA and ÷2. CHF patients presented less and smaller cardiac mitochondria, with disrupted membrane and disorganized cristae when compared to the control group (p<0.001). Skeletal muscle from the CHF group presented mitochondria reduced in number and volume, alterations that were similar to those described for the heart. A correlation between both parameters (mitochondrial number and volume) was also obtained for the control group. The enzymatic activity of CIII complex (2.01 10-2 ± 3.1 10-3ìm.min-1/mg prot) significantly decreased in cardiac tissue from the CHF group in comparison to the control one (p<0.001) as well as in the skeletal muscle: 3.658 10-2 ± 4.0 10-3 ìm.min-1/mg prot for CHF patients and CIII: 1.518 10-1 ± 5.2 10-3 ìm.min-1/mg prot for the control group (p<0.05). Recent studies have suggested that oxidative stress is related to heart failure. Here we found structural and functional alterations of cardiac mitochondria in the CHF group, which contributes to explain the systolic dysfunction that these patients present. In addition, they were associated with a decrease in complexes III enzymatic activity, which generates more reactive oxygen species, causing additional mitochondrial damage and probably stimulating the beginning of apoptosis. We also found a correlation between mitochondrial functional and structural alterations from cardiac and skeletal muscle samples. These findings are a contribution to the knowledge of the CHF physiopathology and would allow to obtain cellular information of the heart using a skeletal muscle biopsy.