Abstract 1575: Proteomic Profile Of Differentially Regulated Proteins In Human Myocardium Before and After Cardiac Surgery Utilizing Cardioplegia and Cardiopulmonary Bypass.
Introduction: Although highly protective, cardiac surgery utilizing cardioplegia and cardiopulmonary bypass(CP/CPB) subjects myocardium to hypothermic reversible ischemic injury that can impair cardiac function. Pronounced contractile deficits in a subset of patients can result in a greatly enhanced risk of mortality. Changes in myocardial contractile activity are likely regulated via acute protein modifications. We performed the following study to determine changes in the protein profile of human myocardium following CP/CPB.
Methods: Right atrial appendage was collected from patients pre and post-CP/CPB. Atrial tissue lysates were subjected to two-dimensional electrophoresis, coomassie total protein staining, gel averaging, and densitometry using 2-D image analysis software. 10 of the most prominently regulated protein spots following CP/CPB were identified using Mass Spectrometry.
Results: Pre-CP/CPB, 32 unique or preferentially expressed (vs post-CP/CPB) protein spots were detected. Post-CP/CPB, 119 differential proteins (vs pre-CP/CPB) were detected. There were no consistent changes in the remaining 289 detected proteins. Identified proteins that changed either expression or post-translational modification following CP/CPB included: contractile proteins MLC-2a and MLC-1, metabolic proteins ATP-synthase F1 complex-delta and Enoyl-CoenzymeA hydratase, the redox-sensitive glutathione-s-transferase omega, the inflammatory proteins alpha-1-acid-glycoprotein and S100A8, and the protesome subunit beta 6. Of particular interest was phosphatidylethanolamine-binding protein 1(PEBP/HCNP), a secreted protein with recently identified potent negative inotropic effects.
Conclusions: Cardiac surgery results in dramatic changes in the human myocardial protein profile. CP/CPB modifies specific cytoskeletal, metabolic, inflammatory, and proteolytic proteins potentially involved in myocardial contractile deficits. Specifically, analysis of the role of PEBP may have significant implications for CP/CPB-induced myocardial stunning.