doi: 10.1161/CIRCULATIONAHA.104.531152
(Circulation. 2005;112:2912-2920.)
© 2005 American Heart Association, Inc.
Cardiovascular Surgery |
Transcriptomic and Proteomic Patterns of Systemic Inflammation in On-Pump and Off-Pump Coronary Artery Bypass Grafting
From the Department of Anesthesiology and Intensive Care Medicine, Friedrich-Schiller-University, Jena (V.T., S.R., R.A.C., F.B., K.B., F.B., K.R., M. Bauer); the SIRS-Lab GmbH, Jena (V.T., S.R., E.M., M. Blaess, H.-P.D.); the Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig (M. Bruegel, J.T.); and the Department of Cardiothoracic and Vascular Surgery, Friedrich-Schiller-University, Jena (J.W., T.W.), Germany. Dr Deigner is now at the School of Chemical Science and Pharmacy, University of East Anglia, Norwich, UK.
Correspondence to Prof Dr Michael Bauer, Department of Anesthesiology and Intensive Care Medicine, Friedrich-Schiller-University, Erlanger Allee 101, D-07740 Jena, Germany. E-mail michael.bauer{at}med.uni-jena.de
Received December 21, 2004; revision received July 14, 2005; accepted July 19, 2005.
Background— Coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) provides controlled operative conditions but induces a whole-body inflammatory response capable of initiating devastating morbidity and mortality. Although technically more demanding, deliberate avoidance of CPB in off-pump surgery attenuates the physiological insult associated with CABG.
Methods and Results— To systematically assess the molecular mechanisms underlying the better-preserved remote organ function, we studied gene expression patterns in leukocytes and plasma proteomic response to on-pump and off-pump CABG. Proteomic analysis confirmed (tumor necrosis factor-
, interleukin [IL]-6, IL-10) and expanded (eg, interferon [IFN]-
, granulocyte colony–stimulating factor [G-CSF], monocyte chemotactic protein-1, macrophage inflammatory protein-1ß) the mediators released on CPB, whereas blood leukocyte transcriptomics suggested that circulating leukocytes are not primarily responsible for this response. Interestingly, release of some cytokines (eg, IL-6, IFN-, G-CSF) was observed on off-pump surgery to a similar extent but with delayed kinetics. A total of 45 of 4868 transcripts were identified to be significantly altered as a result of initiation of CPB. Systematic analysis of transcriptional activation by CPB revealed primarily genes involved in inflammation-related cell–cell communication (such as L-selectin or intercellular adhesion molecule-2) and signaling (such as IL-1, IL-8, or IL-18 receptors and toll-like receptors 4, 5, and 6), thus confirming a "primed" phenotype of circulating peripheral blood mononuclear cells.
Conclusions— Gene array and multiplex protein analysis, only in concert, can illuminate the molecular mechanisms responsible for systemic sequelae of CPB and indicate that circulating leukocytes overexpress adhesion and signaling factors after contact with CPB, which potentially facilitates their trapping, eg, in the lungs and may promote a subsequent tissue-associated inflammatory response.
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M. J. O'Dwyer, E. Duggan, and T. Ryan Letter Regarding Article by Tomic et al, "Transcriptomic and Proteomic Patterns of Systemic Inflammation in On-Pump and Off-Pump Coronary Artery Bypass Grafting" Circulation, May 16, 2006; 113(19): e765 - e765. [Full Text] [PDF]
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V. Tomic, S. Russwurm, R.A. Claus, F.M. Brunkhorst, K. Bode, F. Bloos, K. Reinhart, M. Bauer, E. Moller, M. Blaess, et al. Response to Letter Regarding Article by Tomic et al, "Transcriptomic and Proteomic Patterns of Systemic Inflammation in On-Pump and Off-Pump Coronary Artery Bypass Grafting" Circulation, May 16, 2006; 113(19): e766 - e766. [Full Text] [PDF]
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