Alpha1-adrenergic Receptor mRNA and Inflammatory Mediator Expression in Circulating Leucocytes after Cardiac Surgery

Abstract

Vasodilation after coronary artery bypass surgery is a common complication. Inflammatory mediators influence the expression of alpha1-adrenergic receptors. Do patients requiring high doses of postoperative inotropic support have down-regulated alpha-adrenergic receptors? Is there a characteristic pattern of preoperative inflammatory mediator expression that could predict a complicated course after the operation? Forty-four patients undergoing cardiac bypass surgery with extracorporeal circulation were prospectively investigated. Five perioperative blood samples were taken (preoperative, two hours, 12 hours, 36 hours and 72 hours postoperative). The leucocyte mRNA-expression of the three alpha1-adrenergic receptor subtypes (A, B and D) and 11 different pro-inflammatory mediators were investigated with the real-time reverse transcriptase polymerase chain reaction. The patients were divided into three groups (No-noradrenaline [No-NA]=0 μg/min, Low-noradrenaline [Low-NA]=0.1-7 μg/min, High-noradrenaline [High-NA] >7 μg/min), according to their postoperative noradrenaline requirements. Preoperatively, alpha1 A-receptor expression was 4.9-fold (High-NA) and 18.7-fold (Low-NA) higher than the No-NA group (P=0.005) and plasma noradrenaline levels were higher in the High-NA group (P=0.005). Across all groups at 12 hours after the operation, alpha1 A-receptor expression decreased to approximately one-fifth of preoperative levels (P=0.01); but with greater duration and magnitude of relative decrease in the High-NA group. Patients in the No-NA group had significant postoperative increases in leucocyte inflammatory mediator expression for IL-1ß, TLR4, TREM, MPO, MMP9 and TNF genes, whereas the changes in the Low-NA and High-NA groups were not significant. Low preoperative levels of noradrenaline and low expression of alpha1 A-adrenoreceptors in leucocytes was associated with less probability of requiring noradrenaline support after cardiac surgery.

Vasoplegia after cardiopulmonary bypass: A narrative review of pathophysiology and emerging targeted therapies

“…21 In extrapolating experimental evidence from animal models of septic shock, it is also conceivable that altered alpha-1 adrenergic receptor expression may contribute to catecholamine resistance. 22…”