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Neurogenic pulmonary edema in rats with spinal cord injury
Šedý, Jiří ; Syková, Eva (advisor) ; Herget, Jan (referee) ; Rokyta, Richard (referee)
N urogenic puhnonary edema (NPE) is an acu te life-threatening complication of the c ntral nervous system (CNS) injury. Anesthetics can either promote or inhibit the NPE development. We examined the role of different concentrations of isoflurane anesthesia (1.5 - 3%) on the developmen t of NPE in rats with balloon compressed spinal cord. The development of NPE was examined in vivo and on histological sections of lung tissue. Neurological recovery in animals anesthetized with 1.5% or 3% isoflurane was monitored using BBB and pian tar tests for 7 weeks post-injury. The grade of the spinal gray and white matter sparing was evaluated using morphornetry. The r le of gradually developed spinal cord lesíon and spínal cord transection in the developmen t of NPE were evaluated also. NPE developed in all animals anesthetized with 1.5-2% isofluran . Almost 42% of animals died due to massive pulmonary bleeding and suffocation; X-ray imaging, pulmonary index and histological sections showed massive NPE. More than 71 % of animals anesthetized with 2.5-3% i oflu rane had no signs of NPE. Blood pressure rose more rapidly in animals from 1.5% group than in 3% group; this hypertensive reaction was caused by the sympathetic hyperactivi ty. Animals from 3% group recovered their motor and sensory func tions more rapidly than...
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Reactivity of pulmonary vessels to hypoxia
Koubský, Karel ; Herget, Jan (advisor) ; Červenka, Luděk (referee) ; Neckář, Jan (referee)
Hypoxic pulmonary vasoconstriction (HPV) is a physiological mechanism that maintains optimal oxygenation of blood in the lungs. However, chronic hypoxia causes hypoxic pulmonary hypertension (HPH). Increased reactive oxygen species (ROS) participate in the pathogenesis of HPH. Oxidative stress can cause NO synthase uncoupling and subsequent production of superoxide instead of NO. Increase in intracellular Ca2+ concentration in pulmonary smooth muscle cells is required for pulmonary vasoconstriction. However, vessel tone can also be regulated by vascular smooth muscle cells' calcium sensitivity (without Ca2+ concentration changes). Increase of calcium sensitivity plays a role in HPV and HPH. This study focuses on three mechanisms to influence the increased calcium sensitivity in HPV a HPH: (1) Rho kinase inhibition, (2) effort to re-couple NO synthase, and (3) vasorelaxant effect of tyrosine kinase inhibitors. Normobaric hypoxic chamber (10% O2) or the combination of hypoxia and vascular endothelial growth factor receptor blockade was used to induce pulmonary hypertension in rats. (1) The effect of acute and chronic Rho kinase inhibition was studied on pressure-flow relationship (P/Q) in isolated perfused lungs. Acute Rho kinase inhibition decreased the basal tone of pulmonary vessels in HPH...
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Pes equinovarus:New Treatment Strategies and Pathogenetic Mechanisms
Ošťádal, Martin ; Herget, Jan (advisor) ; Vízek, Martin (referee) ; Poul, Jan (referee)
Idiopathic pes equinovarus (also referred to as clubfoot) is a congenital deformity of the foot and lower leg; it has five components: equinus, varus, adductus, cavus and supination of the foot. At present two principle methods are mostly used for the treatment of clubfoot: physiotherapy and continuous motion without immobilization and the Ponseti method (serial manipulation, cast application, Achilles tenotomy and transposition of m. tibilalis ant.). This method has been reported to have short-term success rates approaching 100%, and the long-term results have been equally impressive. We believe, however, that the data on the success rate may be significantly influenced by the duration of the period after termination of the treatment. The purpose of the first part of our study was, therefore, to compare the short-term (up to three years) and long-term (three to seven years) results of treatment of idiopathic clubfeet with the Ponseti method and to determine the factors for recurrence. We have tested the hypothesis whether is it possible to cure all clubfeet with the Ponseti method only. We have found significant difference between the evaluation of the short- term and long-term results: the number of relapses during the first three years of treatment, indicated for surgical intervention, was...
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The role of oxygen radicals in the early phase of exposure to hypoxia in the development of hypoxic pulmonary hypertension
Lachmanová, Věra ; Herget, Jan (advisor) ; Geršl, Vladimír (referee) ; Neckář, Jan (referee)
A pulmonary vascular bed is low-pressure system at adult subjects. Pulmonary vessels react to hypoxia by two different processes. These are hypoxic pulmonary vasoconstriction (HPV) and hypoxic pulmonary hypertension (HPH). They differ in mechanism of origin, but there seems to be important role of reactive oxygen species and nitric oxide. It was assumed in the past that HPV is isolated reaction of small pulmonary arteries to acute hypoxia and HPH to chronic hypoxia. Recently we believe that HPH is developed on the basis HPV (Crossno, Garat et al. 2007) and remodelation of peripheral pulmonary vessels (Reid 1986). Our main task was to learn, whether antioxidants given in the early phase of exposure to hypoxia influence pulmonary hypertension more than its late administration, in the period of already developed damage of pulmonary vessels. We have used N-acetyl-L-cysteine (NAC) as an antioxidant substance. We measured changes in resistance of pulmonary vascular bed, changes of reactivity of pulmonary vessels in dependence on concentration of oxygen in the inhalated air. Measurements were performed on the model of rat isolated perfused lungs. In addition we have observed influence of the early and late treatment of NAC on the pulmonary artery pressure at rats kept in hypoxic conditions. Our results show that...
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Endothelin and renin - the angiotensin system and its relation to hypertension and hypertension organ damage
Dvořák, Pavel ; Červenka, Luděk (advisor) ; Herget, Jan (referee) ; Janda, Jan (referee) ; Tesař, Vladimír (referee)
Renin-angiotensin and endothelin system play important role in blood pressure regulation. ln order to determine the contribution of an interaction between ET-I and ANG II to the development of hypertension and related end-organ damage in an ANG lI-dependent model of hypertension, we utilized a rat strain transgenic for the mouse Ren-2 renin gene (TGR; strain name TGR(mRen2)27). All our experimental studies have confirmed the crucial effect of increased natrium intake in a diet on development of arterial hypertension and hypertensive end- organ damage (especially kidneys and heart) in this model of arterial hypertension. Previous studies have demonstrated the presence of several types of endothelin system receptors - ETA and ET6 receptors with two subtypes- ETBl and ET62. Our study has brought a new knowledge of physiologic and pathophysiologic function of these receptors. The non- selective blockade of ETA and ETB receptors by Bosentan, improves survival rate of both homozygous and heterozygous transgenic animals, declines extent of hypertensive cardiac end-organ damage and reduce proteinuria and glomeru losclerosis. However, this positive effect of nonselective endothelin blockade is not caused due to decrease of arterial blood pressure. The reason for this fact is probably in various effects of...
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Experimental pulmonary embolism - pathophysiological aspects
Mizera, Roman ; Herget, Jan (advisor) ; Lischke, Robert (referee) ; Vízek, Martin (referee)
- Experimental pulmonary embolism, pathophysiological aspects MUDr. Roman Mizera Theoretical part of the thesis deals with mechanisms of pulmonary hypertension after pulmonary embolism (PE) and summarizes the knowledge of literary sources in this issue. Peripherally deals with the mechanical obstruction of pulmonary vessels, particularly discusses vasoconstriction after the PE. In the experimental part are described three separate experiments. The first experiment tested effect of reactive oxygen species (ROS) and preventive administration their scavenger - superoxide dismutase inhibitor tempol on basal perfusion pressure, vasoconstriction, NO synthase activity and the production of NOx after acute PE. Results show that after PE grows NO synthase activity and the production of NOx, the administration of tempol reduces basal perfusion pressure and vasoconstriction after PE. In the second experiment, we measured basal perfusion pressure and vasoconstriction after PE in lungs exposed to 5 day chronic hypoxia. We tested influence of PDE-5 inhibitor sildenafil on the pulmonary vessels tone. Sildenafil decreased basal pressure after PE in chronic hypoxia, its administration does not affect the pulmonary vasoconstriction of pulmonary vessels, but increases their compliance. The last project tested effect...
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Role of KCNQ channels in response of the pulmonary circulation to hypoxia
Šedivý, Vojtěch ; Herget, Jan (advisor) ; Melenovský, Vojtěch (referee) ; Neckář, Jan (referee)
Reaction of pulmonary vascular bed to hypoxia is different than in systemic vasculature. Acute ventilatory hypoxia constricts pulmonary arteries (HPV), diverts blood to better oxygenated alveoli and optimises arterial pO2. Chronic hypoxia causes pulmonary hypertension (HPH) and exposure to hypoxia at birth (perinatal hypoxia) results in longterm changes of pulmonary vasculature, which makes it more susceptible to develop pulmonary hypertension in adulthood. Reaction of pulmonary artery smooth muscle cells (PASMCs) to hypoxia involves membrane depolarization by inhibition of voltage gated potassium channels (Kv). Among them KCNQ (Kv7) channels have biophysical properties (low voltage threshold for activation and lack of inactivation during sustained depolarization) which suggest them to play a key role in hypoxic response. Specific KCNQ channel inhibitor linopirdine primes HPV in saline perfused lungs, but in not primed lungs does not cause vasoconstriction, it behaves in the same way as acute ventilatory hypoxia. Moreover, in primed lungs linopirdin potentiates HPV and prevents non- specific Kv inhibitor 4-aminopyridine to potentiate HPV. It seems, that KCNQ channel inhibition has a key role in HPV. In rats exposed to hypoxia for 3-5 days (normobaric chamber, FiO2 0,1) we examined relationship of...
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Relationship between pulmonary function and function of the diaphragm in patients with obstructive pulmonary disease
Hellebrandová, Lenka ; Bunc, Václav (advisor) ; Smolíková, Libuše (referee) ; Herget, Jan (referee)
Problém: Obstrukce dýchacích cest a průtoková limitace, způsobená chronickou obstrukční plicní nemocí (CHOPN) nebo astma bronchiale (AB), může způsobit změny tvaru, pozice a pohybů bránice v důsledku zvýšení plicních objemů. Hypotézy: U pacientů s obstrukčním respiračním onemocněním se bude funkce bránice lišit oproti kontrolní skupině zdravých jedinců, což se projeví na jejím postavení a rozsahu pohybu. Existuje vztah mezi plicními funkcemi a polohou a pohyby bránice. Cíl: Cílem práce bylo zjistit, zda pozice, tvar a pohyby bránice u ležících pacientů s průtokovou limitací během maximálních dechových a posturálních manévrů se liší od tvaru, pozice a pohybů bránice za stejné situace u jedinců bez patologie respiračního systému. Zkoumali jsme rozdíly mezi pacienty s CHOPN, pacienty s AB a zdravými jedinci. Cílem bylo také stanovit tyto vztahy v kontextu vážnosti průtokové limitace, resp. obstrukce dechových cest. Metodika: Soubor tvořily 3 skupiny probandů, celkem 31 dospělých: 10 jedinců s klinicky stabilním AB (5 žen a 5 můžů), 11 jedinců s klinicky stabilním, středně těžkým CHOPN (7 mužu a 4 ženy) a kontrolní skupinu tvořilo 10 zdravých jedinců (5 mužů a 5 žen). Všichni probandi podstoupili komplexní měření plicních funkcí a kardiopulmonální zátežové vyšetření. Bránici jsme vyšetřovali pomocí...
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Cytokines and adipocytokines in surgically ill patients: the role of fat tissue
Teplan, Vladimír ; Gürlich, Robert (advisor) ; Adamec, Miloš (referee) ; Herget, Jan (referee)
Cytokines and adipocytokines have major effect on post-operative prognosis of patients. In obese patients, we find significantly higher expression of proinflammatory mediators. In first part of our project we focus on cytokine expresion after elective abdominal surgery. Abdominal surgery was choosen as model of stress reaction to organism. Our results show, that proinflammatory cytokine expresion was significantly higher in obese patients and especially early elevation of visfatin could be a new marker in diagnosis of postoperative inflammatory complications. Related publications describe methods, design and results of trials. Second part of our poject is focused on patients after kidney transplanation, considering obesity, type of previous dialysis, early postoperative movement a nutrition. Our results show, that there is higher proinflammatory expresion after kidney transplanation with no effect of previous type of dialysis. On the other side early exercise have positive effect on cytokine expresion and decreases ADMA. Related publicatons describe methods, details and results of trials.
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