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Regulatory mechanisms of fetoplacental vasculature in hypoxia
Kafka, Petr ; Cvachovec, Karel (advisor) ; Zoban, Petr (referee) ; Bláha, Jan (referee)
The placenta and the lungs are the only organs that perform a function of blood oxygenation and have a common characteristic - vasoconstriction in response to acute hypoxia. Thus the reaction is in an opposite manner than smooth muscle of systemic arteries does. In this study we focused on the mechanisms that regulate fetoplacental blood vessels in conditions associated with hypoxia. An experimental model of isolated dually perfused rat placenta was used. Our findings demonstrate an essential role of Rho kinase signaling pathway in the mechanism of this hypoxic fetoplacental vasoconstriction (HFPV). Chronic exposure to hypoxia causes a sustain elevation of vascular resistance on fetoplacental blood vessels. It was demonstrated in experiment with low-viscosity salt solution perfusion. Our current results show a significant increase of the fetoplacental vascular resistance with blood perfusion which better reflects in vivo conditions. An increase in fetoplacental vascular resistance may lead to placental hypoperfusion and consequent fetal undernutrition, which is considered one of the key causes of serious fetal and neonatal problems, especially intrauterine growth restriction. Diabetes mellitus is a well-known factor affecting fetal growth. Both chronic hypoxia and diabetes act on vessels partly...
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Fibrinolysis in cardiac surgery and possibillity of its control
Špegár, Ján ; Vaněk, Tomáš (advisor) ; Cvachovec, Karel (referee) ; Stříteský, Martin (referee)
Local and systemic application of tranexamic acid in heart valve surgery: a prospective, randomized, double blind LOST study SUMMARY The study was performed to examine a possible augmentation of systemic administration of tranexamic acid by the additional topical application during heart valve surgery in the post-aprotinin era. One-hundred patients were enrolled in the study and all the patients were given tranexamic acid intravenously. The participants were randomized into two groups (A, n = 49; B, n = 51), and before commencing the sternal suturing, the study solution (group A: 250 ml of normal saline + tranexamic acid 2.5 g, placebo group B: 250 ml of normal saline) was poured into the pericardial cavity. The cumulative blood loss (geometric means [95% confidence intervals]) 4 h after the surgery was 86.1 [56.1, 132.2] ml in group A, and 135.4 [94.3, 194.4] in group B, test for equality of geometric means P = 0.107, test for equality of variances P = 0.059. Eight hours after the surgery, the blood loss was 199.4 [153.4, 259.2] ml in group A, 261.7 [205.1, 334.0] ml in group B, P = 0.130 and P = 0.050, respectively. Twentyfour hours postoperatively the blood loss was 504.2 [436.0, 583.0] ml in group A, 569.7 [476.0, 681.7] ml in group B, P = 0.293 and P = 0.014, respectively. The proportion of patients...
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Hemocoagulation and its influencing of contact with body cavities lining, especially pericardium
Vymazal, Tomáš ; Cvachovec, Karel (advisor) ; Stříteský, Martin (referee) ; Vaněk, Tomáš (referee)
Body cavity surgical procedures have been arising. The surgery is complex and often extending two hours on patiens with serious comorbidities and over 65 years of age. The major cavities are the thorax, abdomen and skull. Any body cavity surgical procedure is accompanied by touch of blood and biological membrane leading to release of tissue factor and effecting clot formation pathways. The blood is due to a clear site of procedure succkled out of a body and in most cases is not transfused back: that is why it does not affect the coagulation pathways. If a masive bleeding is expected a cell - saving machine could be used to recuperate and retransfuse the patient's blood. The cell -saver membrane can separate large molecules and substances (fat, blood clot) but is not able to catch various cytokines and tissue factor. These are associated with clot formation pathways disturbances. Coagulation disorder is very serious leading to a massive hemorrhage which is ussualy treated with allogeneic blood transfusion. Allogeneic blood transfusion is associated with poor wound heeling and higher risk of infection complications in postoperative period. In the first part of my work the influence of coagulation system following contact a patient ́s blood and biological body membrane was evaluated. I also wanted to answer...
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The influence of the treatment of experimental acute liver failure by FPSA/Prometheus on intracranial pressure
Pražák, Josef ; Cvachovec, Karel (advisor) ; Červinková, Zuzana (referee) ; Kieslichová, Eva (referee)
Background: Cerebral edema is a well-known and fatal complication of acute liver failure (ALF). The influence of the treatment by artificial liver devices on the cerebral damage caused by ALF is usually monitored by only measuring the intracranial pressure (ICP). The aim of this work was to determine the influence of Fractionated Plasma Separation and Adsorption (FPSA), nonbiological artificial liver device, on the intracranial pressure. The second goal of this work was to determine the potential role of cerebral microdialysis in monitoring of the efficiency of fractionated plasma separation and adsorption (FPSA) treatment of ALF. Methods: Two types of surgical resection model of ALF were used in two separate experiments in pigs. In the first study data from monitoring of the intracranial pressure of ALF group (animals with ALF only) and FPSA group (animals with ALF treated by FPSA) were compared. In the second study data from monitoring by cerebral microdialysis and ICP of the ALF group (animals with ALF only), FPSA group (animals with ALF treated by FPSA) and SHAM group (animals with only laparotomy) were compared using statistical analyses. Results: In both experiments, the ICP was significantly higher in the ALF group than in the FPSA group from the 9th hour of the experiment. In the second...
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Anesthesia techniques and organ microcirculation
Turek, Zdeněk ; Kaška, Milan (advisor) ; Cvachovec, Karel (referee) ; Šrámek, Vladimír (referee)
(Anesthesia techniques and organ microcirculation) There is an increasing evidence about microcirculatory effects of different intravenous anesthetics both under physiological and specific pathological conditions. This study aimed to investigate the effects of intravenous anesthetics on hepatosplanchnic microcirculation in laparotomized mechanically ventilated rats using Sidestream Dark-field (SDF) imaging. Thirty male Wistar rats were divided into 5 groups (n = 6 each). All rats were initially anesthetized with 60mg/kg pentobarbital (i.p.) for instrumentation. This was followed by either ketamine, propofol, thiopental, midazolam or saline + fentanyl (iv bolus over 5 min. and then maintenance over 90 min.). SDF imaging of the liver and distal ileum microcirculation was performed at the baseline and at t = 5, 35, 65 and 95 min. In propofol group there was increase of functional sinusoidal density (FSD) following induction (+25%, P<0.05) and maintenance at t = 95 min. (+10.3%, P<0.05), in ketamine and midazolam group decrease of FSD was observed after induction (-20.4%, P<0.05; -10.1%, P<0.05) and during maintenance at t = 65 min. (-11.6%, P<0.05; -11.4%, P<0.05) when compared to baseline. Following induction with propofol functional capillary density (FCD) of ileal longitudinal muscle layer increased...
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The use of thromboelastography (TEG) in the evaluation of coagulation in patients on intensive care unit (ICU)
Durila, Miroslav ; Cvachovec, Karel (advisor) ; Stříteský, Martin (referee) ; Kovářová Kudrnová, Zuzana (referee)
Patients in the intensive care unit are in critical condition which is often accompanied by a coagulation disorder. Sepsis as a leading cause of death in critically ill patients may be associated with both hypercoagulable state with microtrombi formation in microcirculation and with increased production of endogenous heparinoids with inhibitory effects on blood clotting. Central venous catheter and arterial catheter are established in patients for hemodynamic monitoring and these are flushed with heparin to prevent their closure. Both inputs are used for blood sampling for laboratory tests such as blood count and coagulation parameters, including thromboelastography (TEG). In the first step of the work, arterio-venous differences in coagulation parameters were investigated in patients with sepsis. Higher concentration of D-dimers and lower antithrombin activity were found in venous blood. This finding can be explained by increased antithrombin consumption in hypercoagulable state and reactive hyperfibrinolysis. Inconsistency in the site of blood sampling may then lead to misinterpretation of the pathophysiological processes in the body. No significant differences were found in TEG parameters. In the second step of the work we examined how heparin commonly used for catheter flushing affects TEG-assessed...
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General Anesthesia and Analgosedation with Combination of new Alfa2 agonists and ketamine - focused on specific situation
Schreiberová, Jitka ; Černý, Vladimír (advisor) ; Cvachovec, Karel (referee) ; Málek, Jiří (referee)
Introduction: Ideally, general anesthesia and analgosedation in specific situations should meet the following requirements: fast and simple induction of analgesia, achievement of the desired suppression of consciousness, minimal cardiovascular effects, preservation of patent airways without the need for mandatory ventilation, and rapid recovery after the application of antagonists. Ketamine is widely used for this purpose, often in combination with benzodiazepines, however, it does possess an undesired psychomimetic effect and lacks a specific antagonist. In veterinary anesthesia ketamine is often used in combination with alfa2 agonists, a group of substances with a favourable pharmacological profile in specific situations from an anesthesiologist's point of view. Ketamine in combination with new representatives of alfa2 agonists may theoretically be a promising new option for this purpose. Aim: In rhesus monkeys experiments to assess 1. immobilization by combination of ketamine with alfa2 agonists, 2. effect of the addition of hyaluronidase to the above mentioned combinations, and 3. the possibility of reducing ketamine dosage through the addition of a small dose of midazolam while maintaining the effect of immobilization. In the clinical part to assess analgosedation with combination of...
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End-of-life decision making and quality of life in critically ill patiens
Pařízková, Renata ; Zavázalová, Helena (advisor) ; Kasal, Eduard (referee) ; Cvachovec, Karel (referee)
The development of intensive care during last several decades has brought the ability to increase patients survival and quality of life (QOL) however new tasks and concerns especially in ethics occured. Emerging imbalance among therapeutical options and economic resources together with false optimism of physicians and public regarding "borderless" possibilities of medicine started the discussion about allocation of resources to patients in whom real hope for improvement of medical status or quality of life could be anticipated. Intensive care can prolong dying often associated with distress and loss of dignity that is in contradiction to ethic principles and the main right of human. Withdrawing organ support techniques that is considered as a futile, inappropriate and without chance to improve clinical outcome is in accordance with ethic rules. In this situation, the principal goal of medicine, preserving life and health is no longer affordable therefore it is necessary to change our effort to ensure basic patient's physical, psychological, social and spiritual needs with accent to respect dignity. The aim of PhD theses was: - to define areas and key principles regarding end-of-life decision (EOLD) making in intensive care, - to identify factores affecting short and long-term outcome (surviving and quality...
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