Abstract 16602: The Clinical Significance of Mif, Mif-2 and Mif Genotype in Patients Exhibited to Myocardial Ischemia/reperfusion Injury

Abstract

Background: Cardiac surgery is increasingly been performed on an aging patient population with increased numbers of comorbid conditions. These patients are frequently exposed to myocardial ischemia/reperfusion with deleterious consequences and development of organ dysfunctions. The pleiotropic cytokine macrophage migration inhibitory factor (MIF) is an upstream regulator of the immune response and rapidly released from pre-formed cytoplasmatic pools in response to activating stimuli such as hypoxia, infection or inflammation. Yet, its interaction with related mediators such as its homolog, D-dopachrome tautomerase (MIF-2) is largely unknown. Therefore, we aimed to investigate the interaction and clinical significance of MIF and MIF-2 in patients undergoing cardiac surgery with myocardial ischemia/reperfusion. Methods and Results: Circulating levels of MIF and MIF-2 were measured peri-operatively in 100 patients that underwent elective cardiac surgery and showed a rapid increase upon myocardial ischemia. Intra-operative MIF levels reached maximum during myocardial reperfusion and were independently associated with a reduced risk for the development of AF in the post-operative period (odds ratio 0.99 (0.98-1.00); p=0.007), whereas circulating levels of MIF-2 were associated with an increased frequency of organ dysfunction and predicted the occurrence of atrial fibrillation (area under the curve (AUC)=0.663;p=0.041) and pneumonia (AUC=0.708;p=0.040). Known functional MIF allelic variants were analyzed and patients with high-expression MIF-genotype exhibited reduced incidence of organ dysfunction (3 vs. 25; p=0.042). Conclusion: Our findings present the first description of the kinetics and potential clinical relevance of the MIF, MIF-2 and MIF genotype in myocardial ischemia/reperfusion (I/R) in the setting of cardiac surgery. The present study demonstrated that increased intra-operative MIF levels may provide organoprotective effects, whereas elevated serum levels of MIF-2 were associated with the development of organ dysfunctions in patients after cardiac surgery. Patients with a high-expression MIF genotype experienced a significantly lower incidence of organ dysfunctions.