Abstract 16837: Left Atrium Mitochondria of NYHA Class I Patients With Severe Mitral Valve Regurgitation Display Alterations in H2O2 and Ca2+ Handling: Early Translational Efforts to Define Role of Mitochondria in Human Cardiac Disease
Introduction: Mitral valve regurgitation (MR) results in pronounced left atrial dilatation and hypertrophy. Mitochondrial dysfunction and altered metabolism are associated with cardiac hypertrophy in animal models. The effects of MR on human cardiac mitochondria are unknown, as is whether these effects are localized to the left atrium (LA) or are also present in other cardiac chambers (e.g. right atrium, RA). To address these questions, we investigated whether differences existed in mitochondrial function between LA and RA in patients with severe MR.
Methods: LA and RA biopsies were obtained from patients (n=7) undergoing robotic mitral valve repair surgery. Permeabilized myofibers were prepared from RA and LA samples in order to measure mitochondrial Ca2+ retention capacity, H2O2 emission, basal (V0) and maximal ADP-stimulated (VADP) mitochondrial O2 consumption supported by palmitoyl-carnitine (lipid), pyruvate and succinate (carbohydrate).
Results: All patients underwent successful repair and were documented to have a dilated LA. Marked differences in mitochondrial H2O2 and Ca2+ retention capacity between LA and RA were observed (Figure 1). Data of repeated experiments performed on LA and RA in each patient are denoted by connecting line. ** P < 0.05 In addition, palmitoyl-carnitine VADP was reduced by 30–40%, while succinate VADP was increased ∼25% in LA compared to RA mitochondria (P<0.05). Pyruvate VADP was similar between LA and RA.
Conclusions: This is the first study showing discrete, isolated mitochondrial dysfunction in LA of patients with severe MR. LA mitochondria displayed the metabolic signature of cardiac hypertrophy (i.e. decreased capacity for fatty acid oxidation). Furthermore, the increased mitochondrial H2O2 emission and decreased Ca2+ retention capacity in LA compared to RA may predispose to further LA dysfunction, including atrial fibrillation, as seen in patients with long-standing, severe MR.
- Mitochondrial energetics, heart failure, arrhythmias
- Mitral regurgitation
- Reactive oxygen intermediates
- © 2010 by American Heart Association, Inc.