Abstract 18067: Mitochondrial Biology and Energetics Before and After Left Ventricular Assist Device Support in End Stage Heart Failure Patients
End stage heart failure (HF) is associated with structural and functional perturbations of mitochondria indicating an impaired energy production and oxidative phosphorylation. Patients suffering from HF who have been supported by a left ventricular assist device (LVAD) have shown a significant recovery of their cardiac function, ventricular morphology and myocardial molecular cellular defects. The aim of this study was to elucidate the role of the mitochondria in the functional recovery after LVAD support in end stage HF patients. Accordingly, mitochondria from 5 end stage HF patients were isolated from fresh left ventricular biopsies obtained during LVAD implantation (PRE-VAD). After LVAD support varying from 10 days to 10 months the same patients received a heart transplantation during which a second left ventricular biopsy was obtained (POST-VAD) from the explanted heart. Confirming functional recovery, all patients showed a normalized left ventricular end-diastolic dimension (LVEDD) (65.7 ± 6.2 mm in PRE-VAD vs 42.3 ± 4.3 mm in POST-VAD) shortly after LVAD implantation. Moreover, cardiomyocytes from the POST-VAD samples showed that myofibrillar disarray was augmented compared to their paired PRE-VAD sample. In addition, POST-VAD mitochondria indicated an improved respiratory control (RCI) index and mitochondrial membrane potential (ΔΨ) recovery as compared to PRE-VAD mitochondria. The individual activity levels from ETC I, II, III and V were significantly decreased in all PRE-VAD patients as compared to the ETC activity levels from non-diseased control hearts. Most interestingly, LVAD support recovered the ETC complex activities to the same level of non-diseased control hearts. In contrast, when the ETC activity levels from the POST-VAD samples were compared to biopsies from end-stage heart failure patients without LVAD support, the ETC III, IV and V activity levels did not show any improvement. This study demonstrates the involvement of mitochondrial ETC complexes in the recovery of end stage HF after LVAD support indicating a significant role of mitochondrial metabolism in this phenomenon
- © 2012 by American Heart Association, Inc.