Abnormal Mitochondrial Respiration in Failed Human Myocardium

doi:10.1006/jmcc.2000.1266

Journal of Molecular and Cellular Cardiology

Volume 32, Issue 12, December 2000, Pages 2361-2367

https://doi.org/10.1006/jmcc.2000.1266 Get rights and content

Abstract

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_ADPwas 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_ADPwas 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.

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^☆: Please address all correspondence to: Hani N. Sabbah, Ph.DDirector, Cardiovascular Research, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA. E-mail: [email protected]

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Regular ArticleAbnormal Mitochondrial Respiration in Failed Human Myocardium☆

Abstract

J Am Coll Cardiol

Am J Cardiol

J Mol Cell Cardiol

J Mol Cell Cardiol

J Mol Cell Cardiol

J Mol Cell Cardiol

Am Heart J

Bioch Bioph Acta

J Biol Chem

J Am Cell Cardiol

Chest

J Cardiac Failure

Biochimica et Biophysica Acta

Am J Pathol

Biochem Biophys Acta

J Biol Chem

L Biol Chem

Arch Biochem Biophys

FEBS Letts

Association of depressed myofibrillar adenosine triphosphate and reduced contractility in experimental heart failure

Circ Res

Regular Article
Abnormal Mitochondrial Respiration in Failed Human Myocardium☆