ASSOCIATION OF ENDOTHELIAL INJURY AND SYSTEMIC INFLAMMATION WITH PERIOPERATIVE MYOCARDIAL INFARCTION.

Authors: Aino Ollila (a), Leena Vikatmaa (a), Juha Virolainen (b), Sara Nisula (a), Päivi Lakkisto (c), Ville Pettilä (a) 
Affiliations: Departments of (a) Anesthesiology, Intensive Care Medicine and Pain Medicine, (b) Heart and Lung Center, (c) Clinical Chemistry and Hematology, University of Helsinki and Helsinki University Hospital, PO Box 340, 00029 HUH, Helsinki, Finland.

Background and goal of study
Major surgery predisposes patients to endothelial glycocalyx (EG) injury. EG injury associates with cardiac morbidity [1-3], but its potential association with perioperative myocardial infarction (PMI) is unknown. Accordingly, we investigated the relation of EG injury, systemic inflammation and perioperative myocardial injury/infarction, hypothesizing that the acute EG injury and inflammation are associated with cardiac troponin T (TnT) release and PMI. 

Materials and methods
15 PMI patients and 60 propensity-matched controls were investigated in this prospective study. We measured TnT, EG markers, soluble thrombomodulin (sTM), syndecan-1, vascular adhesion protein 1 (VAP-1), and an inflammatory marker IL-6 preoperatively, 6h, and 24h postoperatively. PMI diagnosis required a significant TnT release and an ischemic sign or symptom. We calculated Spearman’s correlation between TnT, each of the EG markers and IL-6 at preoperatively, 6h, and 24h postoperatively. Comparisons of continuous variables were made using Mann-Whitney U-test. We calculated the Hodges-Lehmann estimator with 95% CIs to measure the magnitude of differences between PMI and non-PMI patients’ values of EG markers and IL-6. The change over time for TnT, EG markers and IL-6 was tested by repeated-measures analysis of variance.  A two-sided p-value <0.05 was considered significant.

Results and discussion
IL-6 levels of PMI patients were significantly higher across all the time points, p=0.002, p=0.002, and p=0.001, respectively. In PMI patients, a significant postoperative IL-6 rise was observed, p<0.001. Preoperative IL-6 correlated positively with preoperative, 6h, and 24h postoperative TnT levels in PMI patients (p=0.05). Further, preoperative IL-6 correlated positively with sTM (p=0.01) in PMI patients. sTM and TnT levels correlated positively at all the time points (p<0.01) in non-PMI patients. 

Conclusion(s)
Systemic inflammation, reflected by IL-6, associates with endothelial injury and PMI. sTM correlated positively with TnT release. The findings should be considered as first hypothesis-generating preliminary evidence regarding the potential association of endothelial glycocalyx injury with PMI and need to be confirmed or refuted in future larger studies.

References
 [1] Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol 2003;23:168-175.
[2] Gokce N. Clinical assessment of endothelial function: ready for prime time? Circ Cardiovasc Imaging 2011;4:348-350.
[3] Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes DR,Jr, Lerman A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 2000;101:948-954.

08 / Association of endothelial injury and systemic inflammation with perioperative myocardial infarction.