Mini bypass and pro-inflammatory leukocyte activation:A randomised controlled trial

Background: Coronary artery bypass grafting (CABG) with conventional cardiopulmonary bypass (CPB) induces systemic inflammation. Miniaturized CPB may attenuate systemic inflammatory activation. The intracellular signalling pathways promoting inflammation in cardiac surgery and the relative effects of CPB on these processes are uncertain. In this study,induction of reactive oxygen species (ROS) and activation of NF-κB,p38 mitogen activated protein kinase (MAPK) within leukocytes and leukocyte accumulation in cantharidin-induced blisters was compared in patients exposed to miniaturized (mCPB) or conventional CPB (cCPB).Methods: Patients undergoing CABG were randomised to receive eitherc CPB (n=13) or mCPB (n=13). Blood samples were collected pre-operatively and five times after initiating CPB (up to 5 hours) and analysed by flow cytometry for intracellular markers of activation (ROS, p38-MAPK and NF-κB phosphorylation).Results: ROS in lymphocytes were elevated in cCPB compared to mCPB (p<0.01) whereas ROS in granulocytes and monocytes were similar between groups.Following initiation of CPB, p38-MAPK was higher in patients receiving cCPB compared to mCPB (p<0.05).NF-κB phosphorylation in leukocyte subsets was similar in patients exposed to cCPB or mCPB. Leukocyte accumulation in cantharidin-induced blisters, white cell counts and serum C-reactive protein were enhanced in response to cardiac surgery, but no differences were observed between mCPB or cCPB groups. Post-operative serum creatinine levels were reduced in the mCPB group compared to cCPB (p<0.05).Conclusion: Both p38-MAPK activation and ROS were attenuated with the use of mCPB compared to cCPB, providing a potential mechanism for reduced inflammation in association with CPB miniaturisation