Perioperative Cardiovascular System Failure in South Asians Undergoing Cardiopulmonary Bypass is Associated with Prolonged Inflammation and Increased Toll-Like Receptor Signaling in Inflammatory Monocytes
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.
