Abstract
Since impaired mitochondrial processes are a cause or sequel of the cardiac failure and cardiomyopathies, the screening of mitochondrial function is necessary to diagnose and understand the pathogenetic basis of the cardiac dysfunction. For this purpose, we have used the skinned fiber technique in combination with high resolution respirometry in human endomyocardial and atrial biopsies obtained from the patients with cardiac failure due to ischemic heart disease, valvular incompetence and aortic stenosis. By applying the multiple substrate inhibitor protocol, the State 3 respiration with pyruvate/malate, glutamate/malate and succinate/rotenone as well as the actractyloside insensitive and the uncoupled respiration were measured in the same permeabilized fiber. In parallel, the kinetics of regulation of the mitochondrial oxidative phosphorylation by ADP was registered in the presence and absence of 20 mM creatine to assess the intactness of the mitochondrial outer membrane (MOM) and coupling between mitochondrial creatine kinase (mi-CK) and adenine nucleotide translocase (ANT), respectively. For these investigations only small amounts of material (few milligrams) were required. The results show that the mean capacity of oxidative phosphorylation was 3–4-fold lower in the atrial myocardium than in the ventricular one. Both muscle groups exhibited normal status of the MOM and coupling between the mi-CK and ANT However, within the groups large variations in the respiratory parameters were observed between the patients. Comparison of individual differences in relation with the corresponding level of cardiac failure and with the mean values of the parameters for the given type of myocardium allows to gain important information regarding the role of disturbances in the respiratory chain and intracellular energy transfer via creatine kinases in each patient.
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Seppet, E. et al. (2003). Mitochondrial Function in Failing Human Myocardium In Vivo: Atrioventricular Differences. In: Singal, P.K., Dixon, I.M.C., Kirshenbaum, L.A., Dhalla, N.S. (eds) Cardiac Remodeling and Failure. Progress in Experimental Cardiology, vol 5. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9262-8_31
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