Defect in oxidative phosphorylation in LV papillary muscle mitochondria of patients undergoing mitral valve replacement.
Mitochondria play a pivotal role in cellular metabolism, especially in energy production. Myocardial function depends on adenosine triphosphate (ATP) supplied by oxidation of several substrates. In the adult heart, this energy is obtained primarily from fatty acid oxidation through oxidative phosphorylation (OXPHOS). With this in view, we studied OXPHOS, Total-ATPase and cytochrome content in the mitochondria of the left ventricular (LV) papillary muscles in excised mitral valves of patients who underwent mitral valve replacement (MVR). The mitochondrial OXPHOS, cytochrome content and ATPase activity were studied in 70 patients (ranging from 22 to 40 years) operated on for mitral valve disease. Control study includes 25 normal mitral valves removed at necropsy from patients who died of extracardiac causes. In the presence of glutamate and succinate as substrates, the rate of mitochondrial oxygen consumption was significantly lower in LV papillary muscles of pathological mitral valves (P<0.001) by using with and without addition of ADP. The ADP/O ratio indices for glutamate and succinate were not significantly affected. Using glutamate as substrate, respiratory control index was significantly raised (P<0.05) as compared with control. A significant reduction of total cytochrome content and ATPase activity (P<0.001) was noted in LV papillary muscles of patients operated for mitral valve disease. Our results showed that OXPHOS, cytochromes 'a', 'b', 'c+c(1)' and ATP activity are significantly impaired in LV papillary muscles in patients with pathological mitral valve. Cardiac mitochondrial oxygen consumption is a very valuable tool to investigate the regulation of cardiac mitochondrial energy metabolism. There is increasing evidence that mitochondrial diseases, such as mitochondrial cardiomyopathy, valvular disease and some myopathies, can be responsive to treatment with metabolic intermediates such as coenzyme Q(10), thiamine, prednisone, and vitamin therapy.
Department of Biochemistry, L.T.M.M.C and L.T.M.G.H., Mumbai 400025, India. santoshshinde2005@yahoo.com
S
S
Santosh
K
K
Pawan
P
P
Karpagam
M
M
Kaushala
P
P
Neela
D000251:Adenosine Triphosphatases / Q000032:analysis / Q000378:metabolism; D016022:Case-Control Studies; D003580:Cytochromes / Q000032:analysis / Q000378:metabolism; D006350:Heart Valve Prosthesis; D006352:Heart Ventricles / Q000033:anatomy & histology*; D006801:Humans; D008931:Mitochondria, Muscle / Q000378:metabolism*; D008943:Mitral Valve / Q000473:pathology* / Q000601:surgery*; D010085:Oxidative Phosphorylation; D010210:Papillary Muscles / Q000378:metabolism*
D003580:Cytochromes; D000251:Adenosine Triphosphatases