Abstract 12656: Expression of Mitochondrial Proteins within the Electron Transport Chain of Hibernating Heart Tissue are Depressed after Successful Revascularization and May Underlie the Mechanism of Persistent Heart Failure
Background: Clinical studies indicate that functional recovery of hibernating myocardium is incomplete following bypass surgery (CABG). Using a swine model of hibernating myocardium in which the proximal LAD is instrumented with a fixed occluder, we hypothesized that failure to increase regional blood flow and function post-CABG may be a result of a persistent decrease in key mitochondrial proteins within the electron transport chain (ETC).
Methods: Seven pigs with hibernating myocardium underwent sternotomy and off-pump revascularization with a left internal mammary artery (LIMA) to the LAD just beyond the chronic stenosis. At 4 weeks, the LIMA anastamosis was patent by multi-detector computer tomography (MDCT) and regional function by ECHO and blood flow by microspheres were assessed at rest and during high dose dobutamine (40 microg/kg/min-iv). ETC protein expression in the LAD and remote region were compared by a proteomic analysis using iTRAQ.
Results: Post-CABG, MDCT confirmed a severe LAD stenosis and patent LIMA graft however regional function and maximal blood flow in the hibernating LAD region during high dose dobutamine was depressed, despite successful revascularization. Commensurate with the reduced maximal blood flow response was a >40% reduction in Complex V, an ATPase within the ETC of mitochondria, that is essential to ATP production at high work states (Figure).
Conclusion: Despite successful revascularization of hibernating myocardium, regional wall thickening and the maximal blood flow response during a catecholamine stress remain depressed. Expression of Complex V, an ATPase within the ETC of mitochondria within hibernating myocardial tissue does not normalize post-CABG. These data suggest that persistent myocardial dysfunction within successfully revascularized hibernating myocardium may arise from a reduced expression of key mitochondrial proteins within the ETC that contribute to a normal energetic state at high work loads.
- Cardiac surgery
- Myocardial revascularization
- Mitochondrial energetics, heart failure, arrhythmias
- Heart failure
- © 2010 by American Heart Association, Inc.