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Protection of the ischemic myocardium during early stages of the ontogenetic development
Doul, Jan ; Charvátová, Zuzana (advisor) ; Adamcová, Michaela (referee) ; Szárszoi, Ondrej (referee)
Neonatal hearts exhibit higher resistance to ischemia-reperfusion (I/R) injury and cannot be further protected by ischemic preconditioning (IPC). Nothing is known about ischemic postconditioning (IPoC) in neonatal hearts yet. Rat hearts isolated on postnatal days 1, 4, 7 and 10 were perfused according to Langendorff. Hearts were exposed to 40 or 60 min of ischemia and reperfusion up to the maximum recovery of developed force. IPoC was induced by protocols 3x10s, 3x30s, 3x60s and 5x10s. Tolerance to ischemia did not change from day 1 to day 4 but decreased to days 7 and 10. On day 10, none of the IPoC protocols 3x10s, 3x30s and 3x60s led to significant protection, not even when the ischemia was prolonged to 60 min. The 3x30s protocol (the most effective from the previous) was also applied on days 1, 4 and 7 without any significant effect. However, in the next series of experiments, protocol 5x10s had significant protective effect on day 10. IPC and IPoC in adult hearts act through mitochondrial- K-ATP channels and nitric oxide (NO). Surprisingly mito-K-ATP blocker (5-HD) administered 5 min before ischemia and during first 20 min of reperfusion had no effect on neonatal resistance or on IPoC on day 10. Another group of hearts was used for analysis of 3- nitrotyrosine (3-NT) and serum samples were...
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The role of energy metabolism in cardioprotection induced by the adaptation to chronic hypoxia
Kolář, David ; Žurmanová, Jitka (advisor) ; Adamcová, Michaela (referee) ; Bardová, Kristina (referee)
Cardiac energy metabolism is the one of the most complex system in the body. To sustain life, but also to respond quickly to any sudden changes (e.g. running, emotional stress), the heart has developed a unique ability and has become a metabolic "omnivore". At physiological conditions, long chain fatty acids (LCFAs) present the major energetic source for the adult myocardium. However, the cardiac energy metabolism may be compromised during pathophysiological states. One of the most dangerous is, undoubtedly, ischaemia-reperfusion injury with its acute form, myocardial infarction. However, the adaptation to chronic hypoxia has been known for decades for its cardioprotective effect against I/R. Changes of cardiac energy metabolism induced by the adaptation have not been fully explored and the system conceals still too many secrets. This thesis has aimed to determine how adaptation to chronic hypoxia affects the cardiac metabolism of the rat LVs in the following set-ups: 1. The effect of chronic normobaric hypoxia (CNH; 3 weeks, 5500m) during a brief I/R protocol in vitro on the protein kinase B/hexokinase (Akt/HK) pathway, including the expression and phosphorylation of Akt, the expression and localization of HK, the expression of mitochondrial creatine kinase (mtCKS), and the level of Bcl-2 family...
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Study of morphological and functional alternations of autonomic cardiac and vessels innervation and its causes in chronic diseases
Mistrová, Eliška ; Chottová Dvořáková, Magdaléna (advisor) ; Vančura, Vlastimil (referee) ; Adamcová, Michaela (referee)
Within the span of few decades, there has been a significant increase in diabetes mellitus and chronic stress in developed countries, such as the Czech Republic. These conditions have a significant negative effect on physical and mental health. Repeated and long-term exposure to raised levels of glucose, overactivity of the sympathetic nervous system and the increase in plasma levels of stress hormones affects most of the organs in the body, including the heart. The cardiovascular system is regulated by a broad number of neurotransmitters, hormones and neuropeptides. Alterations in the innervation of the cardiovascular system, as a result of both diseases, can affect its physiological functions. The present thesis focuses not only on the role of the classic, but primarily on the peptidergic innervation of the heart. The aim was to contribute to the explanation of the impact of neuropeptides and their shared receptor systems on the genesis and the development of heart damage due to diabetes mellitus and/or exposure to stressors. Knowledge of the physiological characteristics of neuropeptides and their involvement in the pathogenesis of both diseases and related complications could be helpful in determining the optimal treatment method or alternatively allow us to use the cardio protective effect of...
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Protection of the ischemic myocardium during early stages of the ontogenetic development
Doul, Jan ; Charvátová, Zuzana (advisor) ; Adamcová, Michaela (referee) ; Szárszoi, Ondrej (referee)
Neonatal hearts exhibit higher resistance to ischemia-reperfusion (I/R) injury and cannot be further protected by ischemic preconditioning (IPC). Nothing is known about ischemic postconditioning (IPoC) in neonatal hearts yet. Rat hearts isolated on postnatal days 1, 4, 7 and 10 were perfused according to Langendorff. Hearts were exposed to 40 or 60 min of ischemia and reperfusion up to the maximum recovery of developed force. IPoC was induced by protocols 3x10s, 3x30s, 3x60s and 5x10s. Tolerance to ischemia did not change from day 1 to day 4 but decreased to days 7 and 10. On day 10, none of the IPoC protocols 3x10s, 3x30s and 3x60s led to significant protection, not even when the ischemia was prolonged to 60 min. The 3x30s protocol (the most effective from the previous) was also applied on days 1, 4 and 7 without any significant effect. However, in the next series of experiments, protocol 5x10s had significant protective effect on day 10. IPC and IPoC in adult hearts act through mitochondrial- K-ATP channels and nitric oxide (NO). Surprisingly mito-K-ATP blocker (5-HD) administered 5 min before ischemia and during first 20 min of reperfusion had no effect on neonatal resistance or on IPoC on day 10. Another group of hearts was used for analysis of 3- nitrotyrosine (3-NT) and serum samples were...
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The role of energy metabolism in cardioprotection induced by the adaptation to chronic hypoxia
Kolář, David ; Žurmanová, Jitka (advisor) ; Adamcová, Michaela (referee) ; Bardová, Kristina (referee)
Cardiac energy metabolism is the one of the most complex system in the body. To sustain life, but also to respond quickly to any sudden changes (e.g. running, emotional stress), the heart has developed a unique ability and has become a metabolic "omnivore". At physiological conditions, long chain fatty acids (LCFAs) present the major energetic source for the adult myocardium. However, the cardiac energy metabolism may be compromised during pathophysiological states. One of the most dangerous is, undoubtedly, ischaemia-reperfusion injury with its acute form, myocardial infarction. However, the adaptation to chronic hypoxia has been known for decades for its cardioprotective effect against I/R. Changes of cardiac energy metabolism induced by the adaptation have not been fully explored and the system conceals still too many secrets. This thesis has aimed to determine how adaptation to chronic hypoxia affects the cardiac metabolism of the rat LVs in the following set-ups: 1. The effect of chronic normobaric hypoxia (CNH; 3 weeks, 5500m) during a brief I/R protocol in vitro on the protein kinase B/hexokinase (Akt/HK) pathway, including the expression and phosphorylation of Akt, the expression and localization of HK, the expression of mitochondrial creatine kinase (mtCKS), and the level of Bcl-2 family...
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|
|
Study of morphological and functional alternations of autonomic cardiac and vessels innervation and its causes in chronic diseases
Mistrová, Eliška ; Chottová Dvořáková, Magdaléna (advisor) ; Vančura, Vlastimil (referee) ; Adamcová, Michaela (referee)
Within the span of few decades, there has been a significant increase in diabetes mellitus and chronic stress in developed countries, such as the Czech Republic. These conditions have a significant negative effect on physical and mental health. Repeated and long-term exposure to raised levels of glucose, overactivity of the sympathetic nervous system and the increase in plasma levels of stress hormones affects most of the organs in the body, including the heart. The cardiovascular system is regulated by a broad number of neurotransmitters, hormones and neuropeptides. Alterations in the innervation of the cardiovascular system, as a result of both diseases, can affect its physiological functions. The present thesis focuses not only on the role of the classic, but primarily on the peptidergic innervation of the heart. The aim was to contribute to the explanation of the impact of neuropeptides and their shared receptor systems on the genesis and the development of heart damage due to diabetes mellitus and/or exposure to stressors. Knowledge of the physiological characteristics of neuropeptides and their involvement in the pathogenesis of both diseases and related complications could be helpful in determining the optimal treatment method or alternatively allow us to use the cardio protective effect of...
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