Endothelial dysfunction mediated by interleukin-18 in patients with ischemic heart disease undergoing coronary artery bypass grafting surgery

Publication date: Available online 8 May 2017
Source:Medical Hypotheses
Author(s): Sokolic Jadranko, Vlatka Sotosek Tokmadzic, Knezevic Danijel, Medved Igor, Vukelic Damjani Nada, Balen Sanja, Rakic Marijana, Lanca Bastiancic Ana, Laskarin Gordana
When medication management or percutaneous coronary intervention is not successful in patients with advanced ischaemic heart disease, surgical revascularisation—predominantly coronary artery bypass grafting (CABG)—is considered the gold standard. However, CABG surgery can lead to ischaemia/reperfusion injury, which is characterized by a strong inflammatory response. Interleukin (IL)-18, is a strong inflammatory mediator, that is released from cardiomyocytes and can be found in the systemic circulation of patients during and immediately after CABG surgery. The existing damage of endothelial glycocalyx in patients with ischaemic heart disease is further impaired concurrently during the surgery due to the anaesthesia-surgical technique used and intravascular fluid loading. This results in the increased incidence of adverse events, including myocardial infarction. IL-18 leads to the activation of lymphocyte cytotoxicity via cytotoxic mediators (Fas ligand, Tumor necrosis factor (TNF)-related apoptosis-inducing ligand, perforin, and granulysin). We hypothesize that IL-18 is released locally in the heart and the systemic circulation in patients undergoing CABG surgery and may be correlated with the level of activity of circulating lymphocytes. In turn, this may lead to lymphocyte-mediated cytotoxicity directed toward damaged and activated endothelial cells. Shear stress glycocalyx, as well as damaged and activated endothelial cells then become the main the source of pro-inflammatory cytokines, chemokines, and adhesion molecules. These attract activated lymphocytes to adhere to the endothelium or enter the subintimal layer, increasing existing or initiating the formation of new plaques, which leads to the development of myocardial infarction during or shortly after surgery. To evaluate our hypothesis, we will measure the local concentration of IL-18 in the sinus coronarius and systemic circulation. These values will then be correlated with immunological and biochemical parameters, predominantly with the concentration of degradation products of glycocalyx and cytotoxic mediators in activated lymphocytes. If our hypothesis is correct, measuring the IL-18 concentration that is responsible for glycocalyx deterioration, may become a useful tool for predicting myocardial infarction occurrence in patients undergoing CABG surgery.



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