Sokolic Jadranko, Tokmadzic Vlatka Sotosek, Knezevic Danijel, Medved Igor, Vukelic Damjani Nada, Balen Sanja, Rakic Marijana, Lanca Bastiancic Ana, Laskarin Gordana
Clinic of Anesthesiology and Intensive Care Medicine, Clinical Hospital Center Rijeka, 51 000 Rijeka, Kresimirova 42, Croatia.
Clinic of Anesthesiology and Intensive Care Medicine, Clinical Hospital Center Rijeka, 51 000 Rijeka, Kresimirova 42, Croatia; Department of Anesthesiology, Reanimatology and Intensive Care, Faculty of Medicine, University of Rijeka, 51000 Rijeka, B. Branchetta 20, Croatia.
Med Hypotheses. 2017 Jul;104:20-24. doi: 10.1016/j.mehy.2017.05.009. Epub 2017 May 8.
When medication management or percutaneous coronary intervention is not successful in patients with advanced ischemic heart disease, surgical revascularisation-predominantly coronary artery bypass grafting (CABG)-is considered the gold standard. However, CABG surgery can lead to ischemia/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 ischemic 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, Tumour 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.
对于晚期缺血性心脏病患者，若药物治疗或经皮冠状动脉介入治疗未取得成功，外科血运重建（主要是冠状动脉旁路移植术，即CABG）被视为金标准。然而，CABG手术可导致缺血/再灌注损伤，其特征为强烈的炎症反应。白细胞介素（IL）-18是一种强烈的炎症介质，由心肌细胞释放，在CABG手术期间及术后即刻可在患者的体循环中检测到。由于所采用的麻醉 - 手术技术及血管内液体负荷，缺血性心脏病患者内皮糖萼的现有损伤在手术期间会进一步加重。这导致不良事件发生率增加，包括心肌梗死。IL-18通过细胞毒性介质（Fas配体、肿瘤坏死因子（TNF）相关凋亡诱导配体、穿孔素和颗粒溶素）导致淋巴细胞细胞毒性激活。我们假设，在接受CABG手术的患者中，IL-18在心脏局部及体循环中释放，且可能与循环淋巴细胞的活性水平相关。进而，这可能导致淋巴细胞介导的细胞毒性作用于受损和活化的内皮细胞。剪切应力糖萼以及受损和活化的内皮细胞随后成为促炎细胞因子、趋化因子和黏附分子的主要来源。这些物质吸引活化的淋巴细胞黏附于内皮或进入内膜下层，增加现有斑块或引发新斑块形成，从而导致手术期间或术后不久发生心肌梗死。为评估我们的假设，我们将测量冠状窦和体循环中IL-18的局部浓度。然后将这些值与免疫学和生化参数相关联，主要是与糖萼降解产物和活化淋巴细胞中细胞毒性介质的浓度相关联。如果我们的假设正确，测量导致糖萼恶化的IL-18浓度，可能成为预测接受CABG手术患者发生心肌梗死的有用工具。
