Mitochondrial respiratory chain activity in idiopathic dilated cardiomyopathy

Background: Cardiomyopathy is well recognized in mitochondrial diseases in which it has been associated with defects of mitochondrial function, includ ing cytochrome-e oxidase (COX) deficiencies. This study explores the respir atory chain activity, particularly of COX, in patients with cardiomyopathy to determine whether a relationship exists between respiratory enzyme activ ity and cardiac function. Methods and Results: Myocardial specimens from the left ventricular wall of explanted hearts were obtained from subjects with ischemic (n = 6) or noni schemic dilated (n = 8) cardiomyopathy. Assays for citrate synthase (CS) an d complexes II/III and IV activity were performed on cardiac mitochondria a nd homogenate. Enzyme activities were normalized to CS activity and compare d with control activities (n = 10). A significant reduction in COX and/or C S activity was identified in mitochondrial preparations from the transplant group and correlated significantly with ejection fraction (P <.05), althou gh this does not prove a causal relationship. Significantly reduced CS acti vity in homogenate was identified, suggesting decreased mitochondrial volum e in addition to decreased COX activity. Measurements in cardiac homogenate s failed to show a significant reduction in COX activity (P >.05) in the tr ansplant group, suggesting that the use of prefrozen tissue homogenates may underestimate existing mitochondrial respiratory defects in cardiac tissue . Conclusions: Mitochondrial function is altered at a number of levels in end -stage cardiomyopathy. Defective COX activity resulting in deficient adenos ine triphosphate generation may contribute to impaired ventricular function in heart failure. Agents capable of improving mitochondrial function may f ind an adjuvant role in the treatment of cardiac failure.