Alterations in Inflammatory Capacity and TLR Expression on Monocytes and Neutrophils After Cardiopulmonary Bypass

Abstract

Cardiopulmonary bypass (CPB) is associated with immune paresis, which predisposes to the development of postoperative sepsis. The aims of this study were to characterize the ex vivo cytokine responses to bacterial cell wall components in whole blood from patients undergoing CPB and to determine whether altered leukocyte expression of Toll-like receptors (TLRs) is involved in immune paresis after CPB. We recruited 6 patients undergoing routine cardiac surgery with CPB. Preoperatively, at the end of CPB and 20 h later, blood was obtained, anticoagulated, and leukocyte surface expression of CD14, TLR2, and TLR4 was quantified by flow cytometry. In addition, blood was incubated at 37 degrees C in the presence of peptidoglycan (PepG) and/or lipopolysaccharide (LPS), and plasma cytokines were measured by enzyme immunoassay. At the end of CPB, ex vivo production of tumor necrosis factor alpha, interleukin (IL) 1beta, IL-8, and IL-10 in response to PepG or LPS was virtually abolished (P < 0.05). The following day, there was recovery of all cytokine responses to PepG. Tumor necrosis factor alpha and IL-1beta responses to LPS partially recovered, whereas IL-8 and IL-10 responses recovered. At the end of CPB, there was more than 50% reduction in neutrophil TLR2 and TLR4 expression (P < 0.05), with recovery to baseline the following day. There was a 29% reduction in monocyte TLR4 expression at the end of CPB (P < 0.05) and more than 120% increase in monocyte TLR2 and 4 expression the following day (P < 0.05). In conclusion, reduced ex vivo production of cytokines cannot be fully accounted for by downregulation of TLR expression, although receptor upregulation may contribute to the later recovery of responsiveness.

Post-cardiotomy extracorporeal cardiopulmonary resuscitation in neonates with complex single ventricle: analysis of outcomes

“…That might reflect high incidence of early withdrawal of support in those with severe end-organ injury after cardiac arrest. Furthermore, longer duration of extracorporeal support has widespread deleterious effects on end-organ systems, which may contribute to later mortality [24]. A significant number of our patients, who died after ECMO discontinuation, died of MOFS or sepsis.…”

“…Recent studies have linked bleeding and increased blood transfusion requirements to decreased hospital survival and substantial morbidity after ECMO [17,24]. Due to our conservative strategy, by judiciously escalating anticoagulation therapy within 48-h period following ECMO, major bleeding complications were limited in our series.…”

Hsp70 and cardiac surgery: molecular chaperone and inflammatory regulator with compartmentalized effects

“…As the latter is associated with circulatory failure and multi-organ dysfunction, the endogenous Hsp70 response thereby prevents the deleterious consequences of deranged systemic inflammation. In this systemic scenario, Hsp70 exerts mainly anti-inflammatory effects on the inflammatory balance through inhibition of pro-inflammatory signaling in leukocytes Hadley et al 2007). Enhanced stress-induced Hsp70 upregulation in inflammatory cells during CPB abrogates NF-κB signaling, thereby leading to immune hyporesponsiveness.…”

Effect of Cardiopulmonary Bypass on Annexin A1 Expression in Peripheral Blood Mononuclear Cells of Children with Congenital Heart Disease

“…After CPB, post-perfusion lung and respiratory failure, liver and kidney dysfunction, gastrointestinal edema and cerebral injury may occur as primary or secondary se qu ences of the inflammation cascade (8,9). CPB can activate the endothelial cells and induce the release of cytokines affecting the prognosis of patients undergoing CPB (10).…”