Carotis stenosis által kiváltott partialis és keringésleállás okozta globalis cerebralis ischaemia-indukálta gyulladásos válasz vizsgálata

Abstract

According to recent statistical analysis, leading causes of mortality in Europe are cardiovascular diseases. 45% of the total mortality has cardiovascular origin. Ischaemic heart disease is the most common form of cardiovascular diseases. Among patients with ischaemic heart disease one of the main cause of mortality is sudden cardiac arrest. The range of incidence of out-of-hospital cardiac arrest is 38-55/100,000/year. Stroke is the second most common cardiovascular disorder in Europe and in other developed regions. A significant proportion of these cases are developed from thromboembolic complications of atherosclerotic lesions of the carotid arteries. The complex diagnostic and therapeutic considerations of extracranial carotid artery stenosis, such as cardiopulmonary resuscitation (CPR) and post-resuscitation care are controlled by international guidelines. Milestones of post-resuscitation care are the optimal target temperature management for favourable mortality and neurogical outcomes and the optimal and reliable prognostication after CPR. One pillar of this later could be the appropriate use of biomarkers. Matrix metalloproteinases (MMPs) are zinc and calcium dependent endoproteinases with specified structure. In the human tissues 23 different MMP were identified. Main role of these are the breakdown of protein structure of the extracellular matrix. Beside this, MMPs play significant roles in complex physiological and pathological processes such as morphogenesis, angiogenesis, and inflammatory response. Four different tissue inhibitors of matrix metalloproteinases (TIMPs) perform the inhibition of MMP activity in human tissues. TIMPs have identified roles in the activation of pro-MMPs and in the regulation of cellular differentiation, morphological development and apoptosis. Near intact cerebral endothelial function, the production of MMPs and other proteinases are minimal. During cerebral ischemic-reperfusion damage the expression of MMPs (mainly MPP-9 and MMP-2) increases significantly. As a result of this process, endothelial and blood-brain-barrier dysfunction and cerebral oedema can be developed. In this doctoral thesis, we aimed to investigate the time courses of MMP-TIMP system during partial and global cerebral ischaemic-reperfusion in connection with elective carotid artery stenting and cardiopulmonary resuscitation. Other aims were the research of the mortality rate, the effects of therapeutic hypothermia and function of protein S100B as a prognostic marker after CPR.