Abstract 19052: Mitochondrial Spatial and Temporal Resolution Before and After Left Ventricular Assist Device Support in Advanced Heart Failure Patients
Background: Advanced heart failure (HF) is associated with structural and functional perturbations in mitochondria, indicating an impaired oxidative phosphorylation. Left ventricular assist device (LVAD) support in HF patients has demonstrated significant recovery of cardiac function and molecular cellular defects. However, comprehensive imaging technologies, demonstrating the spatial and temporal proximities of organellar molecules that improve diagnostic HF stratification in parallel with conventional clinical markers, are still lacking.
Aims: The aim of this study is to explore the recovery of mitochondrial function and molecular structure in advanced HF after LVAD implantation through high-resolution confocal microscopic immunofluorescence (IF) in conjunction with conventional biochemical assays.
Methods: Fresh LV biopsies from 6 patients were obtained during LVAD implantation (PRE-VAD) and during their consecutive heart transplantation (POST-VAD); mitochondria were subsequently isolated.
Results: Confirming functional recovery, all patients showed a normalized left ventricular end-diastolic dimension (LVEDD) (75.7 ± 6.2 mm in PRE-VAD vs 48.3 ± 4.3 mm in POST-VAD) and LV-ejection fraction (LV-EF) (10 ± 0.1% in PRE-VAD vs 25 ± 0.2% in POST-VAD) (P ≤ 0.05) after LVAD implantation. Compared to PRE-VAD, POST-VAD mitochondria indicated an improved respiratory control index (RCI) and mitochondrial membrane potential (ΔΨ) recovery. Furthermore, the diminished individual activity levels from ETC I, II, III and V were significantly recovered. Comprehensive confocal microscopic IF analysis with specific antibodies to ETC subunits NDUF5 (ETC I), SDHF2 (ETC II), Cyc 1 (ETC III), MT-CO1 (ETC IV) and ATP5H (ETC V), as well as the Krebs-cycle enzyme subunit OGDH exhibited an altered spatial distribution pattern in PRE-VAD compared to non-diseased hearts; this alteration was recovered in POST-VAD.
Summary: Our study demonstrates: (i) remarkable functional recovery of mitochondrial ETC complexes in the recovery of advanced HF after LVAD support, indicating a significant role of mitochondrial metabolism, and (ii) spatial and temporal recovery of ETC subunits in HF after LVAD support, observed by high-resolution confocal IF analysis.
Author Disclosures: D.A. Liem: None. J. Mulder: None. M. Skogs: None. S. Setty: None. M. Cadeiras: None. J. Zhang: None. X. Chan: None. A. Lin: None. C. Black: None. E. Larsson: None. A. Asplund: None. E. Lundberg: None. F. Ponten: None. J. Weiss: None. M. Deng: None. J. Odeberg: None. M. Uhlén: None. P. Ping: None.
- © 2014 by American Heart Association, Inc.