Investigation of respiratory chain activity in human heart.

Although disorders of oxidative phosphorylation have long been regarded as neuromuscular diseases only, they can actually give rise to any symptom specifically affecting any organ or tissue, particularly in childhood. The early diagnosis of such a condition may thus require the specific assessment of the mitochondrial function in the organ or tissue shown to be clinically involved. A method is presented allowing such an early detection of respiratory chain defects in human heart. Respiratory chain enzyme studies were carried out using endomyocardial biopsies, less than 2 mg fresh weight. Enzyme activities measured in the endomyocardial biopsies were compared with those obtained using other sampling methods (surgical and postmortem microsamples). A comparison of the respiratory chain enzyme activities in heart and other human tissues is also presented. It was found that (i) the activities of respiratory chain complexes in human heart were similar with any sampling method; (ii) these activities were high compared to other human tissues, allowing the use of heart microsamples for enzyme measurements; (iii) the activity ratios between complexes of the respiratory chain were similar in heart and other human tissues or cells as well, allowing us to confidently characterize potential mitochondrial defects and to compare their expression in different tissues or cells. The value of such investigations on endomyocardial biopsies is illustrated in the case of two patients affected with mitochondrial cardiomyopathy and is discussed in regard to the tissue-specific nature of mitochondrial diseases.