Macrophage Migration Inhibitory Factor Predicts Outcome in Complex Aortic Surgery.

Alexander Gombert,Jochen Grommes,Lukas Martin,Johannes Kalder,Michael Jacobs,Ann Foldenauer,Christian Stoppe,Tobias Schuerholz,Gereon Schälte,Gernot Marx

doi:10.3390/ijms18112374

Abstract

The perioperative inflammatory response is associated with outcome after complex aortic repair. Macrophage migration inhibitory factor (MIF) shows protective effects in ischemia-reperfusion (IR), but also adverse pro-inflammatory effects in acute inflammation, potentially leading to adverse outcome, which should be investigated in this trial. This prospective study enrolled 52 patients, of whom 29 (55.7%) underwent open repair (OR) and 23 (44.3%) underwent endovascular repair (ER) between 2014 and 2015. MIF serum levels were measured until 72 h post-operatively. We used linear mixed models and ROC analysis to analyze the MIF time-course and its diagnostic ability. Compared to ER, OR induced higher MIF release perioperatively; at 12 h after ICU admission, MIF levels were similar between groups. MIF course was significantly influenced by baseline MIF level (P = 0.0016) and acute physiology and chronic health evaluation (APACHE) II score (P = 0.0005). MIF level at 24 h after ICU admission showed good diagnostic value regarding patient survival [sensitivity, 80.0% (28.4–99.5%); specificity, 51.2% (35.1–67.1%); AUC, 0.688 (0.534–0.816)] and discharge modality [sensitivity, 87.5% (47.3–99.7%); specificity, 73.7% (56.9–86.6%), AUC, 0.789 (0.644–0.896)]. Increased perioperative MIF-levels are related to an increased risk of adverse outcome in complex aortic surgery and may represent a biomarker for risk stratification in complex aortic surgery.

Highlights

Macrophage migration inhibitory factor (MIF) is a proinflammatory chemokine-like cytokine that plays critical roles in multiple inflammatory conditions [1,2]
Open repair (OR) requires aortic clamping, which may be associated with risk of spinal cord ischemia (SCI), acute kidney injury (AKI), mesenteric ischemia, or lung injury [13,14]
As coronary artery disease (CAD) is associated with a state of chronic inflammation, it is likely that a stimulus for MIF release has a greater effect in patients with CAD than in those without CAD

Summary

Introduction

Macrophage migration inhibitory factor (MIF) is a proinflammatory chemokine-like cytokine that plays critical roles in multiple inflammatory conditions [1,2]. In atherosclerosis, MIF activates CXCR2 and CXCR4, playing a major role in regulating inflammatory cell recruitment. In contrast to these negative pro-inflammatory and pro-atherogenetic effects, MIF release during myocardial ischemia/reperfusion or cardiac surgery is reportedly associated with reduced organ failure and improved patient outcome [7,8,9]. Both open and endovascular thoracoabdominal aortic aneurysm (TAAA) repair is related to high rates of morbidity and mortality [10,11,12]. Endovascular repair (ER) of complex TAAA still carries mortality rates of 2–21% [18,19], and is associated with morbidity (e.g., AKI or SCI) [13]

Methods

Results

Conclusion