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: Sébastien Trop, John C Marshall, C David Mazer, Milan Gupta, Daniel J Dumont, Annie Bourdeau, Subodh Verma
• Journal: The Journal of surgical research (J Surg Res) Vol. 187 Issue 1 Pg. 43-52 (Mar 2014) ISSN: 1095-8673 [Electronic] United States
• PMID: 24176205 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Cytokines
• TLR2 protein, human
• TLR4 protein, human
• Toll-Like Receptor 2
• Toll-Like Receptor 4

Topics

• Aged
• Asia, Southeastern
• Asian People (statistics & numerical data)
• Biomarkers (metabolism)
• Cardiopulmonary Bypass (adverse effects, mortality, statistics & numerical data)
• Cardiovascular System (immunology)
• Cytokines (blood, immunology)
• Female
• Humans
• Inflammation (ethnology, mortality)
• Male
• Middle Aged
• Monocytes (immunology, metabolism)
• Prospective Studies
• Signal Transduction (immunology)
• Systemic Inflammatory Response Syndrome (ethnology, immunology, mortality)
• Toll-Like Receptor 2 (immunology, metabolism)
• Toll-Like Receptor 4 (immunology, metabolism)
• White People (statistics & numerical data)