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The role of ATP-MgCl2 in ischemia-reperfusion and sepsis
Nalos, Marek ; Kasal, Eduard (advisor) ; Matějovič, Martin (referee) ; Šrámek, Vladimír (referee)
The previously reported multiple beneficial effects of ATP-MgCl2 were tested in two clinically relevant large animal models. We observed mainly cardiovascular effects of ATP-MgCl2 likely related to purinergic receptors stimulation. Adding ATP and its metabolite adenosine to ex vivo LPS stimulated whole human blood cultures and measuring cytokine secretion we have further tested whether modulation of inflammation might be responsible for some of the ATP-MgCl2 effects. The results are summarized as follows: 1. Infusing ATP-MgCl2 intravenously in a porcine I-R injury model of thoracic aortic cross clamping provides better cardiovascular stability compared to currently used standard agent sodium nitroprusside. Although ATP-MgCl2 led to reduced gut lactate release we could not demonstrate any beneficial effects on numerous markers of reperfusion injury. Moreover the combination of sodium nitroprusside with esmolol provided hemodynamic control superior to ATP-MgCl2. 2. In long term hyperdynamic porcine model of sepsis ATP-MgCl2 increased portal venous blood flow, reduced ileal mucosal-arterial pCO2 gap and preserved hepatic arterial buffer response as well as metabolic coupling between lactate release from the gut and its utilization by the liver. Despite the beneficial effects of ATP-MgCl2 on hepatosplanchnic...
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Acute kidney injury in critically ill: experimental and clinical approaches
Valešová, Lenka ; Matějovič, Martin (advisor) ; Nalos, Marek (referee) ; Kieslichová, Eva (referee)
Acute kidney injury (AKI) complicates more than one third of intensive care unit admissions and is burdened by high morbidity and mortality of affected patients, with incidence steadily rising. Sepsis is the leading cause of AKI in critically ill. Despite growing insights into the pathogenesis of sepsis- induced AKI, we are so far not able to define successful AKI prevention and treatment. We aimed at assessing molecular mechanisms of sepsis- induced AKI using clinically relevant large animal model of sepsis and implementing new techniques of molecular biology- genomics and proteomics. Although acidosis is a common acid base disorder in critically ill, its role remains controversial. It is unknown whether acidosis is a marker of disease severity or is directly implicated in pathogenesis of acute organ dysfunction states. Its protective role is discussed with growing evidence of acidosis induced cellular energetics downregulation and reduced oxygen demand in stress conditions. We aimed to evaluate physiological effects of different types of acidosis on healthy organism on systemic and regional level, including a complex research of its effects on kidney to search for new AKI preventive and treatment modalities, which permissive acidosis could represent. Key words Acute kidney injury - sepsis -...
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Acute kidney injury in critically ill: experimental and clinical approaches
Valešová, Lenka ; Matějovič, Martin (advisor) ; Nalos, Marek (referee) ; Kieslichová, Eva (referee)
Acute kidney injury (AKI) complicates more than one third of intensive care unit admissions and is burdened by high morbidity and mortality of affected patients, with incidence steadily rising. Sepsis is the leading cause of AKI in critically ill. Despite growing insights into the pathogenesis of sepsis- induced AKI, we are so far not able to define successful AKI prevention and treatment. We aimed at assessing molecular mechanisms of sepsis- induced AKI using clinically relevant large animal model of sepsis and implementing new techniques of molecular biology- genomics and proteomics. Although acidosis is a common acid base disorder in critically ill, its role remains controversial. It is unknown whether acidosis is a marker of disease severity or is directly implicated in pathogenesis of acute organ dysfunction states. Its protective role is discussed with growing evidence of acidosis induced cellular energetics downregulation and reduced oxygen demand in stress conditions. We aimed to evaluate physiological effects of different types of acidosis on healthy organism on systemic and regional level, including a complex research of its effects on kidney to search for new AKI preventive and treatment modalities, which permissive acidosis could represent. Key words Acute kidney injury - sepsis -...
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The role of ATP-MgCl2 in ischemia-reperfusion and sepsis
Nalos, Marek ; Kasal, Eduard (advisor) ; Matějovič, Martin (referee) ; Šrámek, Vladimír (referee)
The previously reported multiple beneficial effects of ATP-MgCl2 were tested in two clinically relevant large animal models. We observed mainly cardiovascular effects of ATP-MgCl2 likely related to purinergic receptors stimulation. Adding ATP and its metabolite adenosine to ex vivo LPS stimulated whole human blood cultures and measuring cytokine secretion we have further tested whether modulation of inflammation might be responsible for some of the ATP-MgCl2 effects. The results are summarized as follows: 1. Infusing ATP-MgCl2 intravenously in a porcine I-R injury model of thoracic aortic cross clamping provides better cardiovascular stability compared to currently used standard agent sodium nitroprusside. Although ATP-MgCl2 led to reduced gut lactate release we could not demonstrate any beneficial effects on numerous markers of reperfusion injury. Moreover the combination of sodium nitroprusside with esmolol provided hemodynamic control superior to ATP-MgCl2. 2. In long term hyperdynamic porcine model of sepsis ATP-MgCl2 increased portal venous blood flow, reduced ileal mucosal-arterial pCO2 gap and preserved hepatic arterial buffer response as well as metabolic coupling between lactate release from the gut and its utilization by the liver. Despite the beneficial effects of ATP-MgCl2 on hepatosplanchnic...
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