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The role of renal dysfunction in pathophysiology of congestive heart failure progression: preclinical animal studies
Kala, Petr ; Veselka, Josef (advisor) ; Štengl, Milan (referee) ; Štěrba, Martin (referee)
The role of renal dysfunction in pathophysiology of congestive heart failure progression: preclinical animal studies. Abstract The thesis describes effects and pharmacological targets of eicosanoids, especially epoxyeicosatrienoic acids (EETs) that are epoxygenase metabolites of arachidonic acid (AA), in animal model of congestive heart failure (CHF) induced by volume overload via aorto- caval fistula (ACF) in hypertensive transgenic rats (TGR). Our data show that ACF TGR exhibits tissue deficiency of EETs in the left ventricle and kidney, probably mainly caused by increased EETs degradation by soluble epoxide hydrolase (sEH). Treatment by orally active EETs analogue (EET-A) improved the survival rate in ACF TGR compared to placebo. However, after adding EET-A to angiotensin-convertase enzyme inhibitor (ACEi) treatment, the survival of ACF TGR only tended to improve compared with the effects of EET-A or ACEi given alone. The protective effects of EET-A treatment were mediated by improving cardiac parameters and reducing lung congestion, not dominantly by renal mechanisms. We also found that among male (not in female) the combination of sEH inhibitor (sEHi) and ACEi treatment worsened the mortality of ACF TGR compared to ACEi monotherapy. Our data support the notion that targeting the CYP-dependent...
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Non-invasive diagnosis of involvement of the right ventricle in hypertrophic cardiomyopathy
Zemánek, David ; Veselka, Josef (advisor) ; Málek, Ivan (referee) ; Pudil, Radek (referee)
Aim: The ~ulhor invesugatcd thc utility of !traio, ,trajo ratc, and tissue Doppler imagiDg (lDI) forthe evaluation oftbc right vcntticlc (RV) impainnenl io paritOU with a h)'P"nmphic c.rdiomyopathy (HCM) .flt;r ll. IUCOCSIIful alCQhoI ~ptal ablo.tÍOQ wilhout RV hypcrtrOphy in oompari$on wilh C<XI.trolgroup. Mcthodl &lid RCSllII",: A group ol 19 plllÍCOl! sufl"erin, fmm IleM with 22 controls was compaml. The parametcra of TOl M:re evaluated in mitral IIOd lricuspid annulUI. SlrIIm lnd Anno BIC derivW from ml wcre I5Sessed in lUl apH.:al fret:waU ofRV, u wcLl KS in ""!lilI SCgolCflts ofthc len vcntriclc. lktwcen bulh groupS, !bere wcrc statlstically 8ignificant difTerencc~ only III ;,ovolumic pre- ejoction ume (79.2±11.3 ml vs 58.5±8.1 ros, JK{l.OI), iSDVOlulOk ,-e!ll)tllio!1 time (HI4.7±26.2 ms vs n .ll24.5 ms, p<O.OI), m~lalperfOl"TT\3l)(;e(Tci)tndex mcasurcd fmm TOl (O.6I±O.14 Vll 0.49J.0.09, ~.Ol). and early peak diastoli<: veloc:ity of TOl ( 11 .2±1.8cm1I1'112.'»2.6cmll;~.05). CooclU$ion: Tbc: rcsul" IiUg&cJt the impainnent ofboth J)'$lOIi<: and diastolic RV f,metlon in palients rutfering frum HCM. TOI-relaled paramctcrs appcar more Be\lBilivc than ,rmin and I traln Rte for evalUlltion.
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Structural and functional impacts of infective endocarditis
Pazderník, Michal ; Šochman, Jan (advisor) ; Veselka, Josef (referee) ; Beneš, Jiří (referee)
Despite more recent advances in both medical and surgical therapies, the syndrome of infective endocarditis (IE) continues to be characterized by serious complications, and remains a life-threatening infection. According to data from the World Health Organization, the Czech Republic has one of the highest mortality rates due to this disease worldwide. Despite the severity of illness in this country, very few data have been reported previously regarding investigations of IE in the Czech Republic. Consequently, a retrospective evaluation of local IE cases at one of the country's largest medical centers was conducted. Our aim was to analyze the characteristics of this disease in our country. The greatest interest was devoted to Staphylococcus aureus (S. aureus), etiological agent that has been associated with the worst course of IE episodes. The hypothesis of our study was that infective endocarditis caused by S. aureus, in comparison with other etiological agents, is associated with worse course of the disease. We evaluated the structural (abscess formation, impaired integrity of heart valves, systemic embolism) and functional (incidence of heart failure and conduction disturbances, in-hospital mortality) manifestations of IE. Of all studied parameters, only embolism and S. aureus as the causative agent were...
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Genetic testing in patients with hypertrophic cardiomyopathy
Bonaventura, Jiří ; Veselka, Josef (advisor) ; Pudil, Radek (referee) ; Gregor, Pavel (referee)
Introduction: Hypertrophic cardiomyopathy (HCM) is characterised by marked heterogeneity both in phenotype and genotype. One of the main objectives in medical care is early HCM diagnosis and prevention of cardiovascular events including sudden cardiac death (SCD). In a large number of patients, we do not detect any pathogenic or likely pathogenic (P/LP) variant within molecular genetic analysis. Since the genomic testing is time consuming, expensive and difficult to interpret, the patients should be carefully selected. A proper selection of patients helps to prevent SCD in asymptomatic high-risk patients and reduce the unnecessary preventive steps in low-risk individuals. Hypothesis: There are clinical and morphologic HCM characteristics associated with positive genotype. Objectives: 1) Perform genomic testing in a large cohort of Czech HCM patients 2) Identify clinical and morphologic HCM characteristics associated with positive result of genomic testing (finding P/LP variant) 3) Utilize the clinical and morphologic HCM characteristics to predict the result of genomic testing 4) Facilitate cascade family genetic screening by genotyping HCM probands for early prevention of cardiovascular events before clinically overt HCM 5) Investigate the genotype and outcome of HCM patients treated with ASA...
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Diagnosis of hypertrophic cardiomyopathy with emphasis on genetic testing
Tomašov, Pavol ; Veselka, Josef (advisor) ; Kohoutová, Milada (referee) ; Krejčí, Jan (referee)
Dizertační práce: Diagnostika hypertrofické kardiomyopatie se zaměřením na genetické vyšetření Autor: MUDr. Pavol Tomašov Obor: Fyziologie a patofyziologie člověka Abstract Introduction: Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disease with vast genetic and clinical heterogeneity. Genetic testing of HCM patients is important in determining the etiopathogenesis of the disease and is becoming an integral part of patient care. Aim: The aims of our work included the following implementation of genetic testing in HCM in both basic and clinical research: 1. To identify genetic variants in a novel candidate gene NEBL coding Z-disc protein nebulette in HCM patients. 2. To determine clinical and echocardiographic variables associated with the presence of mutations in the most common sarcomeric genes in the Czech population. 3. To find echocardiographic parameters useful in determining the genotype of relatives before the development of phenotype. Results: In a cohort of 95 patients with HCM we identified a novel genetic variant in a conserved spot of NEBL gene (p.H171R) in one patient. The variant was not found in a control population and was predicted to have a damaging effect on the protein's structure. In a cohort of 48 HCM patients tested for mutations in the most common sarcomeric...
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Structural and functional impacts of infective endocarditis
Pazderník, Michal ; Šochman, Jan (advisor) ; Veselka, Josef (referee) ; Beneš, Jiří (referee)
Despite more recent advances in both medical and surgical therapies, the syndrome of infective endocarditis (IE) continues to be characterized by serious complications, and remains a life-threatening infection. According to data from the World Health Organization, the Czech Republic has one of the highest mortality rates due to this disease worldwide. Despite the severity of illness in this country, very few data have been reported previously regarding investigations of IE in the Czech Republic. Consequently, a retrospective evaluation of local IE cases at one of the country's largest medical centers was conducted. Our aim was to analyze the characteristics of this disease in our country. The greatest interest was devoted to Staphylococcus aureus (S. aureus), etiological agent that has been associated with the worst course of IE episodes. The hypothesis of our study was that infective endocarditis caused by S. aureus, in comparison with other etiological agents, is associated with worse course of the disease. We evaluated the structural (abscess formation, impaired integrity of heart valves, systemic embolism) and functional (incidence of heart failure and conduction disturbances, in-hospital mortality) manifestations of IE. Of all studied parameters, only embolism and S. aureus as the causative agent were...
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Non-invasive diagnosis of involvement of the right ventricle in hypertrophic cardiomyopathy
Zemánek, David ; Veselka, Josef (advisor) ; Málek, Ivan (referee) ; Pudil, Radek (referee)
Aim: The ~ulhor invesugatcd thc utility of !traio, ,trajo ratc, and tissue Doppler imagiDg (lDI) forthe evaluation oftbc right vcntticlc (RV) impainnenl io paritOU with a h)'P"nmphic c.rdiomyopathy (HCM) .flt;r ll. IUCOCSIIful alCQhoI ~ptal ablo.tÍOQ wilhout RV hypcrtrOphy in oompari$on wilh C<XI.trolgroup. Mcthodl &lid RCSllII",: A group ol 19 plllÍCOl! sufl"erin, fmm IleM with 22 controls was compaml. The parametcra of TOl M:re evaluated in mitral IIOd lricuspid annulUI. SlrIIm lnd Anno BIC derivW from ml wcre I5Sessed in lUl apH.:al fret:waU ofRV, u wcLl KS in ""!lilI SCgolCflts ofthc len vcntriclc. lktwcen bulh groupS, !bere wcrc statlstically 8ignificant difTerencc~ only III ;,ovolumic pre- ejoction ume (79.2±11.3 ml vs 58.5±8.1 ros, JK{l.OI), iSDVOlulOk ,-e!ll)tllio!1 time (HI4.7±26.2 ms vs n .ll24.5 ms, p<O.OI), m~lalperfOl"TT\3l)(;e(Tci)tndex mcasurcd fmm TOl (O.6I±O.14 Vll 0.49J.0.09, ~.Ol). and early peak diastoli<: veloc:ity of TOl ( 11 .2±1.8cm1I1'112.'»2.6cmll;~.05). CooclU$ion: Tbc: rcsul" IiUg&cJt the impainnent ofboth J)'$lOIi<: and diastolic RV f,metlon in palients rutfering frum HCM. TOI-relaled paramctcrs appcar more Be\lBilivc than ,rmin and I traln Rte for evalUlltion.
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