Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 32, Issue 12, Pages 2361-2367Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1006/jmcc.2000.1266
Keywords
heart failure; mitochondrial respiration; myocardial energy metabolism
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Funding
- NHLBI NIH HHS [HL-49090-06] Funding Source: Medline
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Chronic heart failure (HF) is associated with morphologic abnormalities of cardiac mitochondria including, hyperplasia, reduced organelle size and compromised structural integrity. In this study, we examined whether functional abnormalities of mitochondrial respiration are also present in myocardium of patients with advanced HF. Mitochondrial respiration was examined using a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles obtained from myocardium of failed explanted human hearts due to ischemic (ICM, n = 9) or idiopathic dilated (IDC, n = 9) cardiomyopathy. Myocardial specimens from five normal donor hearts served as controls (CON), Basal respiratory rate, respiratory rate after addition of the substrates glutamate and malate (V-SUB), state 3 respiration (after addition of ADP, V-ADP) and respiration after the addition of atractyloside (V-AT) were measured in scar-free muscle bundles obtained from the subendocardial (ENDO) and subepicardial (EPI) thirds of the left ventricular (LV) free wall, interventricular septum and right ventricular (RV) free wall. There were no differences in basal and substrate-supported respiration between CON and HF regardless of etiology. V-ADP was significantly depressed both in ICM and IDC compared to CON in all the regions studied. The respiratory control ratio, V-ADP/ V-AT, was also significantly decreased in HF compared to CON. In both ICM and IDC, V-ADP was significantly lower in ENDO compared to EPI. The results indicate that mitochondrial respiration is abnormal in the failing human heart. The findings support the concept of low myocardial energy production in HF via oxidative phosphorylation, an abnormality with a potentially impact on global cardiac performance. (C) 2000 Academic Press.
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