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(Circulation. 2008;118:S24-S31.)
© 2008 American Heart Association, Inc.

Myocardial Protection, Perioperative Management, and Vascular Biology

Pilot Proteomic Profile of Differentially Regulated Proteins in Right Atrial Appendage Before and After Cardiac Surgery Using Cardioplegia and Cardiopulmonary Bypass

Richard T. Clements, PhD; Gary Smejkal, MS; Neel R. Sodha, MD; Alexander R. Ivanov, PhD; John M. Asara, PhD; Jun Feng, MD, PhD; Alexander Lazarev, PhD; Shiva Gautam, PhD; Venkatachalam Senthilnathan, MD; Kamal R. Khabbaz, MD; Cesario Bianchi, MD, PhD; Frank W. Sellke, MD

From the Department of Surgery (R.T.C., N.R.S., J.F., S.G., V.S., K.R.K., C.B., F.W.S.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass; Proteomics and Small Molecules Applications Laboratory (G.S., A.L.), Pressure Biosciences, West Bridgewater Mass; Harvard NIEHS Center for Environmental Health Proteomics Facility (A.R.I.), Harvard School of Public Health, Boston Mass; and the Division of Signal Transduction (J.M.A.), Beth Israel Deaconess Medical Center and the Department of Pathology, Harvard Medical School, Boston, Mass.

Correspondence to Frank W. Sellke, MD, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, LMOB 2A, 110 Francis St, Boston, MA 02215. E-mail fsellke{at}bidmc.harvard.edu

Background— Although highly protective, cardiac surgery using cardioplegia and cardiopulmonary bypass (CP/CPB) subjects myocardium to hypothermic reversible ischemic injury that can impair cardiac function which results in a greatly enhanced risk of mortality. Acute changes in myocardial contractile activity are likely regulated via protein modifications. We performed the following study to determine changes in the protein profile of human myocardium following CP/CPB.

Methods and Results— Right atrial appendage was collected from 8 male patients pre and post-CP/CPB. Atrial tissue lysates were subjected to 2-dimensional electrophoresis, total protein staining, gel averaging, and quantitative densitometry. Ten prominent spots regulated in response to CP/CPB were identified using mass spectrometry. Two hundred twenty-five and 256 protein spots were reliably detected in 2D-gels from pre- and post-CP/CPB patients, respectively. Five unique (ie, not detected post-CP/CPB) and 17 significantly increased spots were detected pre-CP/CPB. Thirty-four unique and 25 significantly increased spots were detected in the post-CP/CPB group. Identified proteins that changed after CP/CPB included: MLC-2a, ATP-synthase delta chain and Enoyl-CoenzymeA hydratase, glutathione-s-transferase omega, -1-acid-glycoprotein, and phosphatidylethanolamine-binding protein.

Conclusions— Cardiac surgery results in multiple consistent changes in the human myocardial protein profile. CP/CPB modifies specific cytoskeletal, metabolic, and inflammatory proteins potentially involved in deleterious effects of CP/CPB.

Key Words: cardioplegia • cardiopulmonary bypass • proteomics