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Allooimmunosensitization in left ventricular assist device recipients and impact on post-transplantation outcome
Urban, Marián ; Netuka, Ivan (advisor) ; Ošťádal, Petr (referee) ; Mrázek, František (referee)
Background: In recent years mechanical circulatory assist devices became an established option in bridging patients with refractory heart failure to heart transplantation. One of the alleged limitations of mechanical devices is a high degree of antibody production with possible deleterious effect on subsequent heart transplantation outcome. Aim: The main goal of this study is to assess the role of antibodies on the outcome of surgical treatment of patients with end- stage heart failure. Method: Firstly, we present a literature review on the current state of knowledge of possible immunologic mechanisms involved in antibody production in left ventricular assist device (LVAD) recipients, new methods of antibody detection, desensitization strategies and overview of published evidence assessing the impact of sensitization on post-transplantation outcome. In the experimental part of our study we prospectively evaluated the presence of anti-Angiotensin II Type 1 Receptor (AT1R) antibodies in 83 Heart Mate II (HMII) recipients who were implanted at our institution between 2008 and 2012 and survived the first 60 days. On-device survival and device malfunction, major infection, major bleeding and neurologic dysfunction were compared between antibody positive and antibody negative recipients. Out of a total...
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Proteomics as a tool for understanding molecular mechanisms of human diseases
Pospíšilová, Jana
Proteomics is a set of analytical methods which enable qualitative and quantitative characterization of the proteome. Expression proteomics quantitatively compares proteomes of cells, tissues, body fluids or other biological materials to find differencies in protein expression and, based on these differencies, to describe the biological processes occuring in investigated organisms. An initial material for expression proteomic studies are complex mixtures containing thousands of proteins, which are analyzed using separation (electrophoretic and chromatographic) methods, and identified, possibly quantified using mass spectrometry. The aim of this Thesis is to demonstrate the application of the tools of expression proteomics in solving diverse challenges in biomedicine. We employed various proteomic approaches and tools for studying molecular mechanisms of human diseases using pacient biological samples, or a model organism and a cell culture. We were conducting three different research projects, namely: A quest for potencial molecular targets for selective elimination of TRAIL-resistant mantle cell lymphoma cells; Investigation of molecular mechanisms of heart failure using a rat model of the disease induced by volume overload; and Searching for diagnostically usable serum biomarkers of ovarian...
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Proteomics as a tool for understanding molecular mechanisms of human diseases
Pospíšilová, Jana ; Petrák, Jiří (advisor) ; Šulc, Miroslav (referee) ; Kovářová, Hana (referee)
Proteomics is a set of analytical methods which enable qualitative and quantitative characterization of the proteome. Expression proteomics quantitatively compares proteomes of cells, tissues, body fluids or other biological materials to find differencies in protein expression and, based on these differencies, to describe the biological processes occuring in investigated organisms. An initial material for expression proteomic studies are complex mixtures containing thousands of proteins, which are analyzed using separation (electrophoretic and chromatographic) methods, and identified, possibly quantified using mass spectrometry. The aim of this Thesis is to demonstrate the application of the tools of expression proteomics in solving diverse challenges in biomedicine. We employed various proteomic approaches and tools for studying molecular mechanisms of human diseases using pacient biological samples, or a model organism and a cell culture. We were conducting three different research projects, namely: A quest for potencial molecular targets for selective elimination of TRAIL-resistant mantle cell lymphoma cells; Investigation of molecular mechanisms of heart failure using a rat model of the disease induced by volume overload; and Searching for diagnostically usable serum biomarkers of ovarian...
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Pulmonary pathophysiology during circulatory support.
Popková, Michaela ; Mlček, Mikuláš (advisor) ; Rohn, Vilém (referee) ; Otáhal, Michal (referee)
Introduction: Left-ventricular (LV) distension and consequent pulmonary congestion are complications frequently discussed in patients with severe LV dysfunction treated with veno- arterial extracorporeal membrane oxygenation (VA ECMO). The goal of this study was to describe the influence of high VA ECMO flows to LV distension, lung hemodynamics, and lung fluid accumulation. Methods of LV decompression were studied to prevent lung edema. Methods: In all experiments porcine models under general anesthesia were used. The effects of high extracorporeal blood flow (EBF) on LV heart work were assessed in a chronic heart failure model. The effects of LV afterload on lung fluid accumulation were evaluated by electrical impedance tomography (EIT) on acute heart failure models. Phase and frequency filtration and mathematical analysis were applied to the raw EIT data. Subsequently, mini- invasive techniques of LV decompression were evaluated for LV work. Results: The stepwise increases of VA ECMO flow improved both hemodynamic and oxygenation parameters. Nevertheless, it also caused distension and increased work of LV. The rise in EBF led to increased pulmonary capillary wedge pressure and lung fluid accumulation assessed by EIT in heart failure. The methods for LV decompression (Impella pump, atrial...
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Life after a heart transplant
Kováčová, Anna ; Kordulová, Pavla (advisor) ; Dynáková, Šárka (referee)
Patients with terminal heart failure that cannot be treated with conventional therapies are indicated for heart transplantation. In acute deterioration, patients can be brought to transplant using a mechanical cardiac support that is able to partially or completely take over the role of the heart and allow the restoration of sufficient cardiac output (Fila et al., 2014). The period before and after transplantation represents a very challenging period for patients, when they feel not only physical, but especially mental and social needs, which change during their phases of life and at the same time affect their entire subsequent experience. The main goal of this diploma thesis was to monitor how the previous implantation of long-term mechanical cardiac support and the subsequent heart transplantation affect the needs and feelings of patients. Respondents were selected from patients who had been implanted with mechanical cardiac support prior to heart transplantation. The diploma thesis contained another five sub- objectives, which dealt with mapping the needs of patients before and after implantation of long- term mechanical cardiac support and after heart transplantation, as well as during compliance with regimen measures, information retrieval and education. For qualitative research, the method of...
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Hemodynamic adaptation mechanisms of heart failure to percutaneous venoarterial extracorporeal circulatory support
Hála, Pavel ; Kittnar, Otomar (advisor) ; Szárszoi, Ondrej (referee) ; Havránek, Štěpán (referee)
Introduction: Venoarterial extracorporeal membrane oxygenation (VA ECMO) is widely used in the treatment of circulatory failure, but repeatedly, its negative effects on the left ventricle (LV) have been observed. The purpose of this study is to assess the influence of ex- tracorporeal blood flow (EBF) on systemic hemodynamic changes and LV performance parameters during VA ECMO therapy of decompensated heart failure. Methods: Porcine models of low-output chronic and acute heart failure were developed by long-term fast cardiac pacing and coronary hypoxemia, respectively. Profound signs of circulatory decompensation were defined by reduced cardiac output and tissue hypoperfusion. Sub- sequently, under total anesthesia and artificial ventilation, VA ECMO was introduced. LV performance and organ specific parameters were recorded at different levels of EBF using an LV pressure-volume loop analysis, arterial flow probes on carotid and subclavian arteries, and transcutaneous probes positioned to measure cerebral and forelimb regional tissue oxygen saturations. Results: Conditions of severely decompensated heart failure led to systemic hypotension, low tissue and mixed venous oxygen saturations, and increase in LV end-diastolic pressure. By increasing the EBF from minimal flow to 5 L/min, we observed a...
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Cardiovascular complications in patients with end-stage renal disease.
Valeriánová, Anna ; Malík, Jan (advisor) ; Zemánek, David (referee) ; Piťha, Jan (referee)
Patients with end-stage renal disease frequently suffer from cardiovascular complications. Many factors contribute to their development: hyperkinetic circulation caused by anaemia, fluid retention and by presence of dialysis arteriovenous access; metabolic changes leading to acceleration of atherosclerosis and increase of vascular stiffness and also fluctuation of blood pressure and organ perfusion during haemodialysis, that cause repeated tissue hypoxia. We performed our research on patients in chronic haemodialysis programme. The project studying long-term patency of dialysis access showed that dialysis graft patency is negatively influenced by presence of coronary artery disease and low serum concentrations of cholesterol. In our studies about tissue hypoxia we proved that haemodialysis patients suffer from hypoxia of cerebral tissue and muscle tissue of the dialysis access arm, and that the hypoxia worsens during dialysis. Factors associated with brain hypoxia are presence of heart failure, higher BNP levels and higher erythrocyte distribution width. One of the serious consequences of brain hypoxia is development of cognitive deficit. Among the negative impact of haemodialysis on the heart, we observed left atrial dysfunction, which is a consequence of long-term remodelling and cannot be...
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Causal interaction analysis of cardiovascular signals
Tiurina, Mariia ; Kolářová, Jana (referee) ; Svačinová, Jana (advisor)
Application of the non-invasive methods to detection of the baroreflex sensitivity is a correct way to evaluate the functions of cardiovascular system. This master’s thesis describes the theoretical informations about the problem of baroreflex sensitivity from anatomical, patalogical and clinical views. Theoretical knowledges are foundation for mathematical description of some methods to detection of baroreflx sensitivity in time, frequency and information dimensions. In the practical part of the master’s theses are presented two methods of BRS detection – sequence method based on finding the specific sequences of time series signals and method of application bivariante autoregressive model. Both of methods are implemented in MATLAB. The results of testing data on real data are discussed.
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MR imaging and MR spectroscopy of human during physical stress (MR spectroscopy imaging, MR diffusometry, MR relaxometry etc.)
Šedivý, Petr ; Hájek, Milan (advisor) ; Haberlová, Jana (referee) ; Vymazal, Josef (referee)
The dissertation is concerned to in vivo phosphorus MR spectroscopy (31 P MRS) and 1 H MR imaging (MRI) of muscle in combination with physical workload. The theoretical part of the thesis describes methodology of 31 P MRS measurement and its clinical use in research of metabolic changes in diabetes, heart failure and peripheral artery disease (PAD). The results of the thesis are divided into methodical and clinical parts. Methodical results deal with the construction of experimental equipment, software modification and development, and show of the reproducibility of the dynamic 31 P MRS. The MRI after exercise was used to the describe involvement of the individual calf muscles to muscle contraction during pedal movement in MR compatible ergometer. The first part of the clinical results of the thesis describes changes in muscle metabolism during diabetes and critical ischemia. In patients with critical ischemia the effect of treatment by angioplasty or transplantation of mesenchymal stem cells was evaluated. In the second part of the clinical results the metabolism of patients with heart failure complicated by sideropenia was studied. In these patients the effect of experimental treatment by iron carboxymaltose was described.
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The role of Arachidonic acid metabolites in cardiovascular system and signaling of heart failure
Liptáková, Andrea ; Žurmanová, Jitka (advisor) ; Holzerová, Kristýna (referee)
Arachidonic acid (AA) is polyunsaturated acid that plays an important role in regulation of physiology, bioenergetic and signalling cascades in the heart. AA released by phospholipase A2-catalysed hydrolysis of membrane phospholipids serves as substrate for cyclooxygenase, lipooxygenase and cytochrome P450 epoxygenase to produce a wide spectrum of lipid second messengers, eicosanoids. These very biologically potent molecules regulate a number of cellular processes in the cardiovascular system and changes in their composition and concentration significantly contribute to heart failure. The aim of this thesis was to summarize current knowledge about the role of AA in failing heart. Keywords : Heart, Arachidonic Acid, Heart Failure, Eicosanoids, Cardiovascular System
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