Biochemical studies of energy production in the failing human heart.

Abstract

Obser-vations in experimental animals have indicated that there may be a bioenergetic defect in the failing heart, characterized by an impairment of oxidative phosphorylation. In the present study, this question was examined in man, making use of myocardial tissues obtained from patients at the time of cardiac operations. Mitochondria were isolated from papillary muscles removed from the ventricle during replacement of the mitral and tricuspid valves in patients with chronic heart failure. Measurement of oxidative phosphorylation gave rations of phosphate utilized to O2 consumed averaging 2. 8 with pyruvate/malate as substrate, and 2. 2 with succinate. Respiratory control ratios, determined both manometrically and polarographically, averaged 7. 1 with pyruvate/ malate, 5. 6 with a-ketoglutarate, and 3. 9 with succinate. Average endogenous ATPase activity was 0. 22 [mu]mole phosphate liberated/min. / mg mitochondrial protein; it rose to 0. 59 with Mg++, to 2. 70 with 2, 4-dinitrophenol, and was completely inhibited by oligomycin. These values are comparable to those reported for normal mitochondria obtained from experimental animals. Examination of myocardial tissue by electron microscopy revealed no apparent mitochondrial abnormality. Creatine phosphate was determined in rapidly frozen ventricular biopsies in patients with heart failure undergoing value replacement. The mean tissue concentration was 4. 0 [mu]moles/g compared to 3. 9 [mu]moles/g in biopsies from patients without heart failure. Similarly, no significant reduction of AT P was found in the failing heart.