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Heart in Sepsis
Harazim, Martin ; Matějovič, Martin (advisor) ; Beneš, Jan (referee) ; Kula, Roman (referee)
Sepsis is the most common cause of death in hospitalized patients. It is a very complex and heterogeneous effort of the body to defeat microbial agents. A worldwide effort remains to understand this process more and develop effective treatment strategies to improve the survival of septic patients. This paper focuses on only a tiny slice of the septic condition - cardiomyopathy occurring during sepsis. This still needs to be explored area to comprehend and raises more questions than answers. My work seeks to answer some of these questions. At the same time, it aims to outline the pathophysiological facts that lead to this clinical entity and discuss in more detail the diagnosis and possible therapeutic interventions. The section dedicated to the actual research focuses on specific options for early diagnosis and influencing mortality during sepsis, especially concerning the administration of beta-blockers. KEYWORDS Sepsis, sepsis-induced cardiomyopathy, beta blockers, BUN
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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 sepsis: phatophysiological and therapeutical aspects
Chvojka, Jiří ; Matějovič, Martin (advisor) ; Kasal, Eduard (referee) ; Maňák, Jan (referee) ; Balík, Martin (referee)
Sepsis and septic shock remain major cause of mortality in non-coronary intenisve care units. Prognosis of septic patiens worsens further in case of concomitant acute kidney injury. Pathophysiological pathways leading to renal dysfunction in sepsis remain unclear despite of enormous experimental and clinical research. Similarly, the role of extracorporeal blood purification techniques as an adjunctive treatment in sepsis is highly controversial. The aim of our study was to dynamically assess renal haemodynamic, microvascular and metabolic responses in a porcine clinically relevant model of septic shock. The same experimental model was used in experiments elucidating potential benefit effects of two distinct haemopurification methods on different biological responses to infectious insult.
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Inflammatory bowel diseases in pregnancy
Koželuhová, Jana ; Matějovič, Martin (advisor) ; Keil, Radan (referee) ; Hep, Aleš (referee)
Inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, can affect mainly young people in their reproductive years. IBD therefore has a major impact on patient's family planning decisions. Management of IBD in pregnancy requires a challenging balance between optimal disease control and drug safety. An unanswered question is the impact of the course of childbirth in women with preexisting IBD regarding anal sphincter function and development of anal or fecal incontinence. To this date there aren't any clinically relevant guidelines for managing childbirth in women with IBD. From gastroenterologist's point of view, a clear indication for Caesarean section (CS) is active perianal disease or active IBD with rectal involvement, a relative indication for CS is ileal-pouch-anal anastomosis (IPAA) or ileal-rectal anastomosis in women after colectomy for refractory UC. Studies have shown a lack of knowledge among both patients and physicians regarding reproductive issues in IBD. The main aim of this thesis was first to assess risk of vaginal delivery in development of anal incontince, second to evaluate the safety of biologic therapy during pregnancy in women with inflammatory bowel disease. We present a study researching the morbidity of children born to mothers treated with biological...
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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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Liver and kidney dysfunction in critically ill patients. Support options and compensation functions
Kroužecký, Aleš ; Matějovič, Martin (advisor) ; Chytra, Ivan (referee) ; Viklický, Ondřej (referee) ; Dostál, Pavel (referee)
22 23 7. Summary The liver and kidney are an important organs involved in a number of biosynthetic, biotransformative, detoxifying, endocrine and immune processes and therefore it is understandable that its dysfunction is associated with adverse outcome of critically ill patients. Hepatic and renal dysfunctions in critical illness are relatively common and occur usually as a component of multiple organ dysfunction syndrome (MODS). Several mechanisms have been proposed to explain the development of MODS. Among these, 1) the hypoxic component resulted from an inadequate oxygen supply to tissues, and 2) cytotoxic effects of various mediators are believed the key elements in the pathophysiology of MODS. From these complex causes of injury are probably the most therapeutically attainable the hemodynamic disturbances and maintenance of adequate organ perfusion pressure using vasopressors is one of the cornerstones of treatment of critically ill patients. Blood flow through organs is autoregulated over a wide range of mean arterial pressure (MAP). There is an agreement that under physiological conditions minimum value of MAP necessary to ensure this autoregulation is about 60- 65 mm Hg. Therefore MAP > 65 mmHg has been recommended as a goal for the vasopressor therapy in sepsis. In critical condition, however,...
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Analysis and identification of proteins in organ dysfunction using proteomic methods
Tůma, Zdeněk ; Matějovič, Martin (advisor) ; Lopot, František (referee) ; Hernychová, Lenka (referee)
Proteomics is the large-scale study of proteins, particularly their structures and functions. Proteomics has been utilized in medicine for investigation of disease mechanisms and biomarker discovery. Instrumental methods cover sample preparation, protein and peptide separation and mass spectrometry. At present, there is no proteomic method that can be used as universal for every sample. Analytical methods need to be adapted and optimized for certain samples. The aim of this work was to create methodic procedures and to interpret results of experimental and clinical research. The first part of the thesis includes experiments utilizing proteomics to study changes in the plasma proteome clinically relevant porcine model of sepsis-induced peritonitis. Proteomic analyzes were also starting methodological strategies in experiments aimed at kidney physiology and pathophysiology of acute kidney injury during sepsis. Renal biopsies were analyzed in order to study the time course of proteome changes caused by sepsis and surgery. The second part of the thesis contains experiments studying biocompatibility. A method for elution of proteins interacting with adsorbents used in extracorporeal liver support system and with hemodialyzer capillaries was prepared. Analysis of proteins adsorbed to polysulfone...
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Hemo elimination method in the treatment of sepsis and early multi-organ dysfunction
Sýkora, Roman ; Matějovič, Martin (advisor) ; Chytra, Ivan (referee) ; Maňák, Jan (referee) ; Šrámek, Vladimír (referee)
The most common cause of death in patients with sepsis/septic shock is deterioration of the function of multiple organs, termed multiple organ dysfunction syndrome. Although our understanding of mechanisms involved in the pathophysiology of sepsis-induced tissue damage has improved substantially, therapy of these syndromes still remains largely supportive. The hallmark of sepsis is an overwhelming systemic production of both pro- and anti-inflammatory mediators leading to generalized endothelial and epithelial damage, microcirculatory-mitochondrial distress, altered endocrine and coagulation homeostasis and cellular immune hyporesponsiveness. Therefore, the hypothesis that modulation of this excessive immunological and biological response to infection might improve patient outcome appears reasonable. Hemoelimination techniques represent biologically plausible way to provide non-specific removal of soluble pro- and anti-inflammatory mediators, although the concept of blood purification in sepsis remains a matter of considerable debate. The aim of this thesis was to elucidate effects of 1) high volume hemofiltration (HVHF) and 2) coupled plasma filtration adsorption (CPFA) in a long-term, hyperdynamic porcine septic shock model, which fulfils the criteria for human sepsis. We hypothesized that both HVHF and...
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Gastrointestinal tract dysfunction in critical ill patients
Balihar, Karel ; Matějovič, Martin (advisor) ; Kula, Roman (referee) ; Martínek, Jan (referee)
Multiorgan dysfunction syndrom is the major driving pathophysiological mechanism of morbidity and mortality in critically ill patients. Gastrointestinal dysfunction usually develops as a result critical illness and it is believed to play a key role in the development and progression of multiple organ dysfunction. Moreover, any primary disorder of the gastrointestinal tract, if severe enough, can lead to a critical state and secondary multiorgan dyfunction. Despite intensive experimental and clinical research, reliable tools for monitoring and evaluation of the severity of gastrointestinal dysfunction remain unknown. In the same line, therapy of this complex pathology remains largely supportive. The aim of this thesis was first to explain the severity of the most common and most serious nosocomial infection of the digestive tract, second to elucidate the safety and effectiveness of the endoscopic dual enteral probe insertion in ventilated critically ill patients, and, third to evaluate new diagnostic tools of the gastrointestinal dysfunction. Finally, we present an ongoing project aimed at investigating esophageal dysfunction in mechanically ventilated critically ill patients.
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