What is the significance of perioperative release of macrophage migration inhibitory factor in cardiac surgery?

Cardiac surgery is associated with release of the pleiotropic cytokine macrophage migration inhibitory factor (MIF). The trigger for MIF release has not yet been elucidated. Owing to its intrinsic antioxidative activity, MIF might reduce oxidative stress and protect from myocardial ischemia and reperfusion (I/R) injury. In the present study, patients scheduled for elective cardiac surgery (n=46) were randomized to undergo coronary artery bypass grafting either conventionally with cardiopulmonary bypass and cardioplegic arrest-induced I/R (cCABG) or in an off-pump procedure (OPCAB) with minimized I/R. We report that only patients who underwent cCABG exhibited a postoperative increase of MIF (p=0.024), while both groups showed an increase in interleukin-6. MIF release appears to be primarily mediated by I/R and to a lesser extent by inflammation. Endogenous peroxidase activity (p=0.021) and serum levels of thioredoxin (p=0.003) were significantly higher in patients who underwent cCABG after surgery. Interestingly, perioperative MIF release was associated with an enhanced antioxidant capacity and a significantly reduced postoperative incidence of atrial fibrillation (p=0.018) and acute kidney injury (p=0.048). The present study highlights the role of MIF increase during cardiac surgery in response to oxidative stress. Based on current observations, we hypothesize that intraoperative MIF secretion is due to I/R and enhances the antioxidant capacity in patients during cardiac surgery.