Abstract 11527: Prolonged Cardiovascular System Failure in South Asians Undergoing Cardiopulmonary Bypass Correlates with Prolonged Inflammation and Increased TLR4-Mediated Signaling
South Asian ethnicity is an independent risk factor for mortality after coronary artery bypass grafting (CABG) surgery which could result from an unrestrained inflammatory response to cardiopulmonary bypass (CPB). This study compared the inflammatory response to CPB in Caucasians and South Asians undergoing CABG surgery. A prospective study of 37 patients (20 Caucasians, 17 South Asians) undergoing CABG surgery with CPB was conducted. Serum levels of pro-inflammatory (IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-18, IFNγ, TNFα) and anti-inflammatory (IL-1RII, sTNFRI) cytokines were measured. The TLR4 signaling pathway was examined by flow cytometry by measuring the serum level of endogenous (HSP60) and exogenous (LPS) TLR4 ligands; surface expression of TLR4 and co-receptor molecules (CD14, sCD14); and activation of downstream messenger molecules (IRAK4, NF-κB, JNK, p38 MAPK, AKT) in monocytes. South Asians had persistently higher serum levels of IL-6 and IL-8, which was associated with increased signaling through TLR4 in inflammatory monocytes following CPB. This increased inflammatory response was associated clinically with a higher Sequential Organ Failure Assessment score (5.1 ± 1.4 v. 1.5 ± 1.6, p = 0.027) and prolonged cardiovascular system failure (23.5% v. 0%) 48 h post CPB. This study demonstrates for the first time that patients of South Asian ethnicity exhibit increased CPB-induced systemic inflammation compared to age and risk factor matched Caucasians and that this response correlates with enhanced perioperative multi-organ failure and low output syndrome. These data provide a biological basis for higher mortality associated with CABG surgery in this population, and suggest that anti-inflammatory therapies could potentially be used to mitigate the adverse consequences resulting from this response.
- © 2011 by American Heart Association, Inc.