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The role of cold acclimation in ischemicko-reperfusion injury
Marvanová, Aneta ; Žurmanová, Jitka (advisor) ; Čížková, Dana (referee) ; Králová Lesná, Ivana (referee)
Cardiovascular disease, including ischemic heart disease, its acute form of myocardial infarction and subsequent heart failure, is still the most common cause of death in the world. For decades, scientists have been aiming to find clinically usable cardioprotective interventions that effectively prevented this disease or reduced the consequences of this disease and improved the quality of life of patients. It is known that a healthy lifestyle, which includes long-term hardening, contributes to heart protection. The beneficial effects of hardening on personality have been known for two hundred years, but no one before us has investigated the effect of a cold environment on the magnitude of ischemia-reperfusion (I/R) damage 10 years ago, we introduced a model of mild cold exposure (8 ± 1 řC) (MCE) which was protective on the size of the myocardial infarction and at the same time no negative side effects such as hypertension and myocardial hypertrophy were demonstrated. Our aim was to investigate the mechanism of cardioprotection induced by MCE. We asked the following questions: What is the metabolic profile of rats exposed to MCE? What is the effect of MCE on the magnitude of I/R damage in the short and long term? When does brown adipose tissue mature during MCE? Which signalling pathways are...
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Ischemia-reperfusion injury in cold acclimated rats
Vebr, Pavel ; Žurmanová, Jitka (advisor) ; Alánová, Petra (referee)
The effect of cold acclimation on body of mammals has been studied for many decades by using relatively low temperatures for acclimation (6-10 řC). The results of these experiments have shown the important role of the adrenergic and thyroid system during acclimation and negative impact on renal system at the same time. In contrast, a recent study on winter swimmers suggests a possibility of positive influence of hardening on cardiovascular system. There is no available study investigating a relationship between cold adaptation and ischemia-reperfusion injury. The aim of this study was to establish a protocol of isolated rat heart and its fixation at our workplace. Furthermore, to find the impact of mild cold acclimation on the ischemia-reperfusion injury of rat. Methods of ex vivo heart perfusion and fixation were successfully established. The effect of 5 weeks long cold acclimation in 10 ± 2 řC on left ventricle ischemia-reperfusion injury was observed. Powered by TCPDF (www.tcpdf.org)
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Ischemia-reperfusion injury in lungs after transplantation and the role of radical oxygen species
Mrázková, Hana ; Lischke, Robert (advisor) ; Třeška, Vladislav (referee) ; Kittnar, Otomar (referee)
Keywords: Lung Tx, EVLP, NHBD, IR injury, ROS, hypercapnia, gender differences This dissertation thesis deals with a very topical issue of the lack of donor organs for lung transplants. As with other organs, the number of patients on waiting lists in terminal stages of their diseases is also constantly rising but there is not an adequate increase in donor organs. We focused our experimental work on the development of research concerning the solution which is most successful in a long-term perspective, i.e. organ transplants from non- heart-beating donors (NHBDs), in an ex vivo lung transplant protocol (EVLP) on an animal model (Wistar rats). This is a method which is clinically established worldwide (in the Czech Republic only experimentally) and is constantly subject to further research. Based on earlier studies, we focused the first experimental part of this work on the potential protective effect of hypercapnic ventilation on ischemia-reperfusion (IR) lung injury in EVLP. The study proved that the hypercapnic ventilation has a protective effect on the generation of reactive oxygen species (ROS) in IR lung injury, but only when used in the period of reperfusion. In the second experimental study, we followed up a very topical issue of the effect of gender on IR lung injury in EVLP in...
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The role of mitochondrial creatine kinase and hexokinase in cardioprotective mechanisms induced by chronic hypoxia
Wasková, Petra
IN ENGLISH The ischemia-reperfusion (I/R) injury, which is a consequence of myocardial infarction, represents a major cause of death worldwide. One of the most effective cardioprotective interventions increasing the resistance of hearts to the I/R injury is the adaptation to a chronic hypoxia (CH). However, the molecular mechanisms of CH are still not well understood. The most important factors responsible for the I/R injury are reactive oxygen species (ROS) produced by complexes I and III within the mitochondrial electron transport chain. Potential candidates maintaining ROS at a low level are mitochondrial creatine kinase (mtCK) and two hexokinase isoforms (HK1 and HK2). These enzymes highly support the mitochondrial oxidative phosphorylation by increasing the availability of ADP for complex V of the respiratory chain. In addition, the HK binding to mitochondria inhibits binding of the pro- apoptotic protein BAX, thereby protecting cardiac cells against apoptosis. Besides the mitochondrial CK isoform, there are two cytosolic CK (CKM and CKB) present in cardiomyocytes that help to maintain energy homeostasis. Based on the known anatomical and physiological differences between the left (LV) and the right (RV) ventricles, the first study focused on the comparing ventricles in terms of the energy...
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Potential physiological significance of thermal preconditioning
Ptáková, Alexandra ; Novotný, Jiří (advisor) ; Benák, Daniel (referee)
Short-term exposure of cells or whole body to mild hyperthermia, known as thermal pre- conditioning, is an experimental method used to provide cytoprotection against subsequent, otherwise harmful or even lethal, stress conditions. Thermal preconditioning is relatively easily feasible and could be used to prevent various health problems. The aim of this thesis is to sum- marize current knowledge about the impact of thermal preconditioning on cells and the whole organism. The possibilities of how to perform this method effectively are described here, toge- ther with the molecular mechanisms involved in the induction of cytoprotection. Some areas where thermal preconditioning could be used are also mentioned. Key words: thermal preconditioning, hyperthermia, cytoprotection, HSP, ischemia-reper- fusion injury
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The role of GPCRs and their signalling systems in cardioprotection
Svobodová, Ivana ; Novotný, Jiří (advisor) ; Holzerová, Kristýna (referee)
G protein-coupled receptors (GPCRs) are a family of membrane receptors with hundreds of members, many of them present in the heart, where their signalling systems are involved in regulation of many cellular processes. An important role of GPCRs is the cardioprotection against cardiac ischemia-reperfusion injury, which mainly involves the so-called RISK pathway containing of kinases signalling for cell survival and against apoptosis. By protecting the heart during ischemia/reperfusion they can prevent irreversible cardiac injury, including myocardial infarction or cardiac dysfunctions, which can lead to heart failure. GPCRs regulate many processes linked to pathophysiology of heart failure - hypertrophy, fibrosis, loss of cardiac function. Understanding the role of individual receptors in these cardioprotective and cardiotoxic processes is essential for the development of new drugs.
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The role of mitochondrial creatine kinase and hexokinase in cardioprotective mechanisms induced by chronic hypoxia
Wasková, Petra
IN ENGLISH The ischemia-reperfusion (I/R) injury, which is a consequence of myocardial infarction, represents a major cause of death worldwide. One of the most effective cardioprotective interventions increasing the resistance of hearts to the I/R injury is the adaptation to a chronic hypoxia (CH). However, the molecular mechanisms of CH are still not well understood. The most important factors responsible for the I/R injury are reactive oxygen species (ROS) produced by complexes I and III within the mitochondrial electron transport chain. Potential candidates maintaining ROS at a low level are mitochondrial creatine kinase (mtCK) and two hexokinase isoforms (HK1 and HK2). These enzymes highly support the mitochondrial oxidative phosphorylation by increasing the availability of ADP for complex V of the respiratory chain. In addition, the HK binding to mitochondria inhibits binding of the pro- apoptotic protein BAX, thereby protecting cardiac cells against apoptosis. Besides the mitochondrial CK isoform, there are two cytosolic CK (CKM and CKB) present in cardiomyocytes that help to maintain energy homeostasis. Based on the known anatomical and physiological differences between the left (LV) and the right (RV) ventricles, the first study focused on the comparing ventricles in terms of the energy...
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Effect of N-acetylcysteine and therapeutic hypothermia on ischemia-reperfusion injury after experimental cardiac arrest
Pinterová, Nikola ; Škulec, Roman (advisor) ; Kučera, Karel (referee)
Therapeutic hypothermia (TH) is the only clinically used intervention that suppresses nearly all manifestations of ischemia-reperfusion injury after cardiac arrest. Experimental models has proven that exogenous antioxidants have positive impact on ischemia-reperfusion injury and it is able to prevent it as well. Results in this thesis are based on application of high dosages of N-acetylcystein (NAC) on ischemia-reperfusion injury after experimental cardiac arrest in a porcine model. It was used as a form of monoteraphy or in combination with TH. During the experiment animals were randomized into 5 groups: administration of NAC and TH (group A), administration of NAC during cardiac arrest (group B), induction of TH (group C), without any intervention (group D) and administration of NAC after return of spontaneous circulation (group E). We were not able to confirm additive effect of NAC in combination with TH. Administration of NAC during cardiac arrest led to statistically important reduction of oxidative stress but in the same time anafylactic reaction led to higher mortality in group B and changes in hemodynamical parameters in group E. Key words: Therapeutic hypothermia, cardiac arrest, N-acetylcysteine, ischemia-reperfusion injury, cardiopulmonary resuscitation, oxidative stress, oxygen radicals
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Ischemia-reperfusion injury in cold acclimated rats
Vebr, Pavel ; Žurmanová, Jitka (advisor) ; Alánová, Petra (referee)
The effect of cold acclimation on body of mammals has been studied for many decades by using relatively low temperatures for acclimation (6-10 řC). The results of these experiments have shown the important role of the adrenergic and thyroid system during acclimation and negative impact on renal system at the same time. In contrast, a recent study on winter swimmers suggests a possibility of positive influence of hardening on cardiovascular system. There is no available study investigating a relationship between cold adaptation and ischemia-reperfusion injury. The aim of this study was to establish a protocol of isolated rat heart and its fixation at our workplace. Furthermore, to find the impact of mild cold acclimation on the ischemia-reperfusion injury of rat. Methods of ex vivo heart perfusion and fixation were successfully established. The effect of 5 weeks long cold acclimation in 10 ± 2 řC on left ventricle ischemia-reperfusion injury was observed. Powered by TCPDF (www.tcpdf.org)
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The role of mitochondrial creatine kinase and hexokinase in cardioprotective mechanisms induced by chronic hypoxia
Wasková, Petra ; Žurmanová, Jitka (advisor) ; Drahota, Zdeněk (referee) ; Nováková, Olga (referee)
IN ENGLISH The ischemia-reperfusion (I/R) injury, which is a consequence of myocardial infarction, represents a major cause of death worldwide. One of the most effective cardioprotective interventions increasing the resistance of hearts to the I/R injury is the adaptation to a chronic hypoxia (CH). However, the molecular mechanisms of CH are still not well understood. The most important factors responsible for the I/R injury are reactive oxygen species (ROS) produced by complexes I and III within the mitochondrial electron transport chain. Potential candidates maintaining ROS at a low level are mitochondrial creatine kinase (mtCK) and two hexokinase isoforms (HK1 and HK2). These enzymes highly support the mitochondrial oxidative phosphorylation by increasing the availability of ADP for complex V of the respiratory chain. In addition, the HK binding to mitochondria inhibits binding of the pro- apoptotic protein BAX, thereby protecting cardiac cells against apoptosis. Besides the mitochondrial CK isoform, there are two cytosolic CK (CKM and CKB) present in cardiomyocytes that help to maintain energy homeostasis. Based on the known anatomical and physiological differences between the left (LV) and the right (RV) ventricles, the first study focused on the comparing ventricles in terms of the energy...
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