title: Transcriptomic and proteomic patterns of systemic inflammation in on-pump and off-pump coronary artery bypass grafting.
abstract: 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.
  
  
  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-alpha, interleukin [IL]-6, IL-10) and expanded (eg, interferon [IFN]-gamma, granulocyte colony-stimulating factor [G-CSF], monocyte chemotactic protein-1, macrophage inflammatory protein-1beta) 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-gamma, 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.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Friedrich-Schiller-University, Jena, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Tomic
authors.forename: S
authors.initials: S
authors.lastname: Russwurm
authors.forename: E
authors.initials: E
authors.lastname: Möller
authors.forename: R A
authors.initials: RA
authors.lastname: Claus
authors.forename: M
authors.initials: M
authors.lastname: Blaess
authors.forename: F
authors.initials: F
authors.lastname: Brunkhorst
authors.forename: M
authors.initials: M
authors.lastname: Bruegel
authors.forename: K
authors.initials: K
authors.lastname: Bode
authors.forename: F
authors.initials: F
authors.lastname: Bloos
authors.forename: J
authors.initials: J
authors.lastname: Wippermann
authors.forename: T
authors.initials: T
authors.lastname: Wahlers
authors.forename: H-P
authors.initials: HP
authors.lastname: Deigner
authors.forename: J
authors.initials: J
authors.lastname: Thiery
authors.forename: K
authors.initials: K
authors.lastname: Reinhart
authors.forename: M
authors.initials: M
authors.lastname: Bauer
mesh_terms: D000818:Animals; D001026:Coronary Artery Bypass / Q000009:adverse effects* / Q000379:methods; D004195:Disease Models, Animal; D004285:Dogs; D004452:Echocardiography; D004558:Electric Stimulation; D007249:Inflammation / Q000209:etiology / Q000235:genetics*; D018408:Patch-Clamp Techniques; D020543:Proteome / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D020543:Proteome