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Myocardial Electrophysiology in Health and Disease
Jarkovská, Dagmar ; Štengl, Milan (advisor) ; Stankovičová, Tatiana (referee) ; Bébarová, Markéta (referee)
This dissertation consists of three parts describing electrophysiological and contractile changes of the myocardium in sepsis, acidosis, and propofol-induced anaesthesia. The first part is focused on heart rate variability analysis in a clinically relevant porcine model of sepsis/septic shock. Heart rate variability showed fast decrease few hours after sepsis induction which preceded changes in clinical parameters commonly used for sepsis diagnosis. The same fast kinetics of heart rate variability were demonstrated in progressive septic shock and in sepsis without serious multiorgan failure. Based on these results, it seems that heart rate variability could represent an early diagnostic tool in patients threatened with sepsis. In the second part of this thesis acidosis and its effects on the cardiovascular system are analysed. Metabolic and hypercapnic acidoses were examined in domestic pigs using hemodynamic in vivo measurements and in vitro experiments focused on electrophysiology and contractility of the heart. Both types of acidosis affected circulation and reduced myocardial contractility; hence it could limit therapeutic use of hypercapnic acidosis. The thesis is completed by a study of the effect of propofol, an anaesthetic used in two above mentioned studies. In rat ventricular tissue in...
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A MODIFIED MATHEMATICAL MODEL OF HUMAN VENTRICULAR CARDIOMYOCYTE INCORPORATING SEPARATE T-TUBULAR AND SURFACE DYADS AND SUBMEMBRANE SPACES
Pásek, Michal ; Bébarová, M. ; Christé, G.
Intracellular Ca2+ load and Ca2+ transient are considerably dependent on distribution of sarcolemmal Ca2+ pump and Na+-Ca2+ exchanger between the t-tubular and surface membranes in the presence of separate dyadic and subsarcolemmal spaces in rat ventricular cell model. To explore analogical phenomenon in human, we modified our previously published model of human ventricular myocyte. When the t-tubular fractions of Na+-Ca2+ exchanger and of sarcolemmal Ca2+ pump were increased to the newly proposed value of 0.95 in the modified model, the following changes were observed at 1 Hz steady-state stimulation: a shortening of the action potential duration at 90% repolarisation by 6% and an increase of the cytosolic Ca2+ transient by 22%. Further analysis revealed a critical role of Ca2+ concentration changes in the subsarcolemmal spaces and consequent change in cellular Ca2+ cycling in this effect.
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Myocardial Electrophysiology in Health and Disease
Jarkovská, Dagmar ; Štengl, Milan (advisor) ; Stankovičová, Tatiana (referee) ; Bébarová, Markéta (referee)
This dissertation consists of three parts describing electrophysiological and contractile changes of the myocardium in sepsis, acidosis, and propofol-induced anaesthesia. The first part is focused on heart rate variability analysis in a clinically relevant porcine model of sepsis/septic shock. Heart rate variability showed fast decrease few hours after sepsis induction which preceded changes in clinical parameters commonly used for sepsis diagnosis. The same fast kinetics of heart rate variability were demonstrated in progressive septic shock and in sepsis without serious multiorgan failure. Based on these results, it seems that heart rate variability could represent an early diagnostic tool in patients threatened with sepsis. In the second part of this thesis acidosis and its effects on the cardiovascular system are analysed. Metabolic and hypercapnic acidoses were examined in domestic pigs using hemodynamic in vivo measurements and in vitro experiments focused on electrophysiology and contractility of the heart. Both types of acidosis affected circulation and reduced myocardial contractility; hence it could limit therapeutic use of hypercapnic acidosis. The thesis is completed by a study of the effect of propofol, an anaesthetic used in two above mentioned studies. In rat ventricular tissue in...
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Blokáda sodíkového a přechodného draslíkového proudu perfenazinem: experimentální a simulační studie
Bébarová, M. ; Matejovič, P. ; Pásek, Michal ; Jansová, D. ; Šimurdová, M. ; Nováková, M. ; Šimurda, J.
The effect of a neuroleptic drug perphenazine on sodium current INa and transient outward potassium current Ito was studied in rat ventricular myocytes at room temperature. Perphenazine reversibly blocked INa (reducing its amplitude; IC50 = 1.24 +/- 0.10 μmol/l, nH =0.99 +/- 0.08) and Ito (accelerating its apparent inactivation with a slight decrease of its amplitude; IC50 = 38.2 +/- 3.5 μmol/l, nH = 0.75 +/- 0.07, evaluated from the changes of time integral). Both INa- and Ito-block was use- and frequency-dependent (20%-increase of INablock and 10%-increase of Ito-block under 0.3 and 10 μmol/l perphenazine, respectively, at the stimulation frequency of 3.3 Hz applied after a 15-s rest). The results of quantitative modelling suggest that perphenazine interacts with INa-channels in inactivated states, and with Ito-channels in both open and open-inactivated states.
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Účinek perphenazinu na přechodný draslíkový proud u komorových buněk potkana
Bébarová, M. ; Matejovič, P. ; Pásek, Michal ; Račkauskas, G. ; Šimurdová, M. ; Šimurda, J. ; Nováková, M.
The aim of this study was to explore the effect of a phenothiazine neuroleptic drug perphenazine on transient outward potassium current Ito in rat ventricular myocytes. Perphenazine reversibly decreased the amplitude and accelerated the apparent inactivation of Ito in a concentration-dependent manner with EC50 = 26.4 +/- 3.5 µmol/l and Hill coefficient n = 0.84 +/- 0.10 (evaluated from changes of time integral of Ito). Time course of Ito-inactivation was well fitted by a double exponential function; the fast time constant was significantly decreased under the effect of perphenazine and its concentration dependence was comparable with the concentration dependence of Ito-block represented by time integrals (EC50 = 26.8 +/- 8.2 µmol/l, n = 0.88 +/- 0.28). It is suggested that perphenazine-induced block via open channel is very likely involved in the mechanism of drug-channel interaction.
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