title: Perioperative cardiovascular system failure in South Asians undergoing cardiopulmonary bypass is associated with prolonged inflammation and increased Toll-like receptor signaling in inflammatory monocytes.
abstract: BACKGROUND
  South Asian ethnicity is an independent risk factor for mortality after coronary artery bypass. We tested the hypothesis that this risk results from a greater inflammatory response to cardiopulmonary bypass (CPB).
  
  
  METHODS
  This was a single-site prospective cohort study. We compared the inflammatory response to CPB in 20 Caucasians and 17 South Asians undergoing isolated coronary artery bypass grafting surgery.
  
  
  RESULTS
  Plasma levels of proinflammatory cytokines (interleukin [IL]-6, IL-8, IL-12, interferon gamma, and tumor necrosis factor) and anti-inflammatory mediators (IL-10 and soluble TNF receptor I) were measured. The Toll-like receptor (TLR) signaling pathway was examined in peripheral blood monocytes by flow cytometry, measuring surface expression of TLR2, TLR4, and coreceptor CD14 and activation of downstream messenger molecules (interleukin-1 receptor-associated kinase 4, nuclear factor kappa from B cells (NF-κB), c-Jun amino-terminal kinase, p38 mitogen-activated protein kinase, and Protein Kinase B). South Asians had persistently higher plasma levels of IL-6 and exhibited increased TLR signaling through the p38 mitogen-activated protein kinase and Protein Kinase B pathways in inflammatory monocytes after CPB. This increased inflammatory response was paralleled clinically by a higher sequential organ failure assessment score (5.1 ± 1.4 versus 1.5 ± 1.6, P = 0.027) and prolonged cardiovascular system failure (23.5% versus 0%) 48 h after CPB.
  
  
  CONCLUSIONS
  South Asians develop an exacerbated systemic inflammatory response after CPB, which may contribute to the higher morbidity and mortality associated with coronary artery bypass in this population. These patients may benefit from targeted anti-inflammatory therapies designed to mitigate the adverse consequences resulting from this response.
authors.affiliation: Clinician Investigator Program, University of Toronto, Toronto, Ontario, Canada; Department of Surgery, Keenan Research Centre in the Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada; Platform of Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Trop
authors.affiliation: Department of Surgery, Keenan Research Centre in the Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada; Interdivisional Department of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: John C
authors.initials: JC
authors.lastname: Marshall
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Anesthesia, Keenan Research Centre in the Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: C David
authors.initials: CD
authors.lastname: Mazer
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Canadian Cardiovascular Research Network, Brampton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Milan
authors.initials: M
authors.lastname: Gupta
authors.affiliation: Platform of Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Dumont
authors.affiliation: Platform of Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Immunology, University of Toronto, Toronto, Ontario, Canada. Electronic address: annie.bourdeau@sri.utoronto.ca.
authors.forename: Annie
authors.initials: A
authors.lastname: Bourdeau
authors.affiliation: Department of Surgery, Keenan Research Centre in the Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada; Department of Surgery, University of Toronto, Toronto, Ontario, Canada. Electronic address: subodh.verma@sympatico.ca.
authors.forename: Subodh
authors.initials: S
authors.lastname: Verma
mesh_terms: D000368:Aged; D001210:Asia, Southeastern; D044466:Asian People / Q000706:statistics & numerical data; D015415:Biomarkers / Q000378:metabolism; D002315:Cardiopulmonary Bypass / Q000009:adverse effects* / Q000401:mortality / Q000706:statistics & numerical data; D002319:Cardiovascular System / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000208:ethnology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D011446:Prospective Studies; D015398:Signal Transduction / Q000276:immunology; D018746:Systemic Inflammatory Response Syndrome / Q000208:ethnology / Q000276:immunology* / Q000401:mortality; D051195:Toll-Like Receptor 2 / Q000276:immunology* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000378:metabolism; D044465:White People / Q000706:statistics & numerical data
chemical_list: D015415:Biomarkers; D016207:Cytokines; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
keywords: Cardiopulmonary bypass; Ethnicity; Inflammation; Molecular markers