Jan Herget

Jan Herget
Charles University in Prague | CUNI

Charles Univ., Prague

About

132
Publications
15,353
Reads
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2,420
Citations
Citations since 2017
4 Research Items
803 Citations
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2017201820192020202120222023020406080100120140
2017201820192020202120222023020406080100120140
2017201820192020202120222023020406080100120140
Additional affiliations
January 1990 - present
September 1970 - September 2015
Charles University in Prague
Position
  • Lecturer, Professor
Description
  • medical Physiology and Pathophysiology
January 1968 - December 1970
The Czech Academy of Sciences
Position
  • PhD Student

Publications

Publications (132)
Article
Full-text available
Hypoxic pulmonary vasoconstriction (HPV) is a beneficial mechanism that diverts blood from hypoxic alveoli to better ventilated areas of the lung, but breathing hypoxic air causes the pulmonary circulation to become hypertensive. Responses to airway hypoxia are associated with depolarisation of smooth muscle cells in the pulmonary arteries and redu...
Article
To test whether macrophages can play any role in hypoxic pulmonary vasoconstriction, we tested the in vitro response of rings from small pulmonary arteries to the activation of macrophages by FMLP, a substance stimulating predominantly membrane-bound NADPH oxidase. A small vessel myograph was used to measure the responses of rings from small pulmon...
Article
Chronic hypoxia causes oxidative injury of pulmonary vessels and attenuates their reactivity to different stimuli. When combined with hypercapnia, biochemical markers of this injury are reduced but the effect of concomitant hypoxia and hypercapnia on vascular reactivity is not fully understood. This study was therefore designed to test whether hype...
Article
Full-text available
Chronic hypoxia induces an increased production of nitric oxide (NO) in pulmonary prealveolar arterioles. Bioavailability of the NO in the pulmonary vessels correlates with concentration of L-arginine as well as activity of phosphodiesterase-5 enzyme (PDE-5). We tested a hypothesis whether a combination of L-arginine and PDE-5 inhibitor sildenafil...
Article
Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthases (NOS). Oxidative stress oxidises BH4 to dihydrobioptein (BH2), resulting in the uncoupling of the two enzymatic domains of NOS and the production of superoxide rather than NO (NOS uncoupling). Oxidative stress is known to be increased in the early stage of chronic hypoxia...
Article
Full-text available
The ultrastructure of the tracheal epithelium in rabbits exposed for 96 hours to 35–37% O2 was studied in our experiments. Due to the influence of mild normobaric hyperoxia, massive differentiation of new secretory elements was initiated and resulted in apparent changes in goblet cells distribution. 60 ± 4% of goblet cells took part in the formatio...
Article
Full-text available
The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the l...
Article
Full-text available
The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the l...
Article
Full-text available
The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the l...
Article
Full-text available
As with other organ transplants even lung transplantation raises the question of the possibility of the influence of gender on ischemia-reperfusion injury. This is a current topic especially for increasingly utilized method of lung transplantation from a non-heart-beating donors, where reperfusion preceded by a period of warm and cold ischemia with...
Article
Full-text available
Exposure to hypoxia, leading to hypoxic pulmonary hypertension (HPH), is associated with activation of alveolar macrophages (AM). However, it remains unclear how AM participate in this process. There are studies which imply that the AM product monocyte chemoattractant protein-1 (MCP-1) plays an important role. Thus we tested: 1. if the selective el...
Article
Two mechanisms contribute in the development of pulmonary hypertension in pulmonary embolism (PE) - obstruction of pulmonary blood vessels and vasoconstriction. We hypothesize that hypoxia, increased shear stress and/or activation of gathered leukocytes in the PE may cause a release of reactive oxygen species (ROS). Therefore our aim was to determi...
Article
Full-text available
Idiopathic pes equinovarus is a congenital deformity of the foot and lower leg defined as a fixation of the foot in adduction, supination, and varus. Although the pathogenesis of clubfoot remains unclear, it has been suggested that fibroblasts and growth factors are involved. To directly analyze the protein composition of the extracellular matrix i...
Article
Full-text available
The present study was performed to evaluate the role of intrapulmonary activity of the two axes of the renin-angiotensin system (RAS): vasoconstrictor angiotensin-converting enzyme (ACE)/angiotensin II (ANG II)/ANG II type 1 receptor (AT(1)) axis, and vasodilator ACE type 2 (ACE2)/angiotensin 1-7 (ANG 1-7)/Mas receptor axis, in the development of h...
Article
Full-text available
The aim of the present study was to test the hypothesis that chronic hypoxia would aggravate hypertension in Ren-2 transgenic rats (TGR), a well-defined monogenetic model of hypertension with increased activity of endogenous renin-angiotensin system (RAS). Systolic blood pressure (SBP) in conscious rats and mean arterial pressure (MAP) in anestheti...
Conference Paper
Full-text available
Chronic ventilatory hypoxia results in remodelling of pulmonary vasculature and hypoxic pulmonary hypertension. Hypoxia increases the turnover of extracellular matrix proteins in peripheral pulmonary blood vessels. We studied hypoxia – induced changes in collagen isolated from pulmonary peripheral arteries and from systemic mesenteric peripheral a...
Article
In male rats, pulmonary hypertension was found 9, 17 to 18, and 30 wk after an intrapulmonary injection of 50 mg quartz dust suspended in saline. Pulmonary arterial blood pressure increased progressively with time, and in the oldest group, the weight of the right heart ventricle was increased.
Article
Full-text available
The vessels on the fetal side of the placenta differ from most other vascular beds except the lungs in that they respond to acute hypoxia by vasoconstriction. An essential role of calcium influx in the mechanism of this hypoxic fetoplacental vasoconstriction (HFPV) has been shown previously. That finding does not, however, exclude the possible invo...
Article
Full-text available
The effect of three-day fasting on cardiac ischemic tolerance was investigated in adult male Wistar rats. Anesthetized open-chest animals (pentobarbitone 60 mg/kg, i.p.) were subjected to 20-min left anterior descending coronary artery occlusion and 3-h reperfusion for infarct size determination. Ventricular arrhythmias were monitored during ischem...
Article
Full-text available
The protective effect of therapeutic hypothermia in cardiac arrest survivors (CAS) has been previously well documented. Animal studies have indicated that attenuation of tissue oxidative stress (OS) may be involved in the mechanisms that lead to the beneficial effect of hypothermia. The extent of OS and nitric oxide (NO) production in adult CAS tre...
Conference Paper
Lungs retrieved from non-heart-beating donors (NHBD) might alleviate the shortage of suitable organs for transplantation. Since hypercapnia has protective effect on free radical damage, in present study we investigated a possible protective effect of hypercapnic ventilation during reperfusion in lungs retrieved from NHBD. Experimental rats underwe...
Article
Full-text available
Pulmonary hypertension resulting from chronic hypoxia is at least partly caused by the increased production of reactive oxygen species (ROS). The goal of the presented study was to investigate the dynamics and the site of production of ROS during chronic hypoxia. In our study Wistar rats were kept for 1, 4 and 21 days in an isobaric hypoxic chamber...
Article
Hypoxic pulmonary hypertension (HPH) is a syndrome characterized by the increase of pulmonary vascular tone and the structural remodeling of peripheral pulmonary arteries. Mast cells have an important role in many inflammatory diseases and they are also involved in tissue remodeling. Tissue hypoxia is associated with mast cell activation and the re...
Article
Full-text available
To characterize the time frame of changes in pulmonary arterial pressure, right ventricular hypertrophy and morphology of small pulmonary arteries male Wistar rats were exposed to isobaric hypoxia (3 weeks, F1O2 0.1) and then let to recover on air for 1 or 5 weeks. Normoxic animals (group N) served as controls. Mean pulmonary arterial pressure (PAP...
Article
Full-text available
Preparations consisting of an isolated perfused lung from small laboratory animals is useful tool to study local regulatory mechanisms in health and disease. Isolated lung can be perfused with blood or with salt solution including albumin for several hours without functional impairment. The basic advantage of this preparation is the good opportunit...
Article
Full-text available
Remodeling of the peripheral pulmonary vasculature during chronic hypoxia is characterized by accelerated collagenolysis and thickening of the vascular wall. Low molecular weight peptides, products of cleavage by interstitial collagenase and muscular layer in the peripheral pulmonary vessels, are typically present. The aim of this "in vitro" study...
Article
Full-text available
Pulmonary vascular remodeling induced by chronic hypoxia regresses after return to normoxia. This regression is associated with an increased amount of collagenase in pulmonary mast cells and increased collagenolytic and elastolytic activity in the lung tissue. The role of lung mast cells during recovery from chronic hypoxia was tested by the inhibi...
Article
Full-text available
Matrix metalloproteinases (MMPs) is a family of proteolytic enzymes involved in remodeling of extracellular matrix. Although proteolytic enzymes are produced by many cell types, mast cells seem to be more important than other types in remodeling of pulmonary arteries during hypoxia. Therefore, we tested in vitro production of MMPs and serine protea...
Article
Full-text available
The restoration of bowel continuity using multiple classic anastomoses is mostly impossible in unstable critically ill extremely low birth weight neonates. The parameters of healing of approximative anastomoses in which integrity and continuity of bowel is achieved with limited number of stitches were evaluated in an experimental study. Small bowel...
Article
Full-text available
Potassium channels are central to the regulation of pulmonary vascular tone. The smooth muscle cells of pulmonary artery display a background K(+) conductance with biophysical properties resembling those of KCNQ (K(V)7) potassium channels. Therefore, we investigated the expression and functional role of KCNQ channels in pulmonary artery. The effect...
Article
We investigated the influence of oxygenation of in vitro lung preparation on the pulmonary vascular reactivity. Small pulmonary vessels isolated from adult male Wistar rats exposed for 4 days to hypoxia (F(iO2) = 0.1, group CH) were compared with those of normoxic controls (group N). The bath in the chamber of small vessel myograph was saturated wi...
Article
Full-text available
Chronic lung hypoxia results in hypoxic pulmonary hypertension. Concomitant chronic hypercapnia partly inhibits the effect of hypoxia on pulmonary vasculature. Adult male rats exposed to 3 weeks hypoxia (Fi(02)=0.1) combined with hypercapnia (Fi(C02)=0.04-0.05) had lower pulmonary arterial blood pressure, increased weight of the right heart ventric...
Article
Full-text available
Chronic hypoxia results in hypoxic pulmonary hypertension characterized by fibrotization and muscularization of the walls of peripheral pulmonary arteries. This vessel remodeling is accompanied by an increase in the amount of lung mast cells (LMC) and the presence of small collagen cleavage products in the vessel walls. We hypothesize that hypoxia...
Article
Several studies report that hypoxic exposure induces free radical oxidative damage in various tissues. The mechanism of this damage includes membrane lipid peroxidation which can be easily detected by measuring fluorescent end-products of the process, i.e. lipofuscin-like pigments. Four day exposure of rats to hypoxia (10% O(2)) increased the level...
Article
Full-text available
Lungs retrieved from non-heart-beating donors (NHBDs) may alleviate the shortage of suitable organs for transplantation. The critical point is the preservation of lungs during warm ischemia, when severe damage is caused by free radicals. We investigated the effect of ventilation, pre-arrest administration of heparin, and the cell-permeable free rad...
Article
Full-text available
An increase in fetoplacental vascular resistance caused by hypoxia is considered one of the key factors of placental hypoperfusion and fetal undernutrition leading to intrauterine growth restriction (IUGR), one of the serious problems in current neonatology. However, although acute hypoxia has been shown to cause fetoplacental vasoconstriction, the...
Conference Paper
Chronic hypoxia damages peripheral pulmonary vessels and causes hypoxic pulmonary hypertension (HPH). According to our hypothesis, the release of reactive oxygen species (ROS), nitric oxide (NO) and products of their interaction contribute to the pathogenesis of HPH. Experimenting with chronic hypoxic adult male rats, we tested the effect of NO and...
Article
Full-text available
Chronic hypoxia induces lung vascular remodeling, which results in pulmonary hypertension. Vascular remodeling is associated with collagenolysis and activation of matrix metalloproteinases (MMPs). One of the possible sources of MMPs in hypoxic lung are mast cells. The role of lung mast cell collagenolytic activity in hypoxic pulmonary hypertension...
Article
A technique of approximative anastomosis in witch integrity and continuity of bowel is achieved with limited number of interrupted seromuscular stitches was evaluated in experimental study. Small bowel anastomosis were performed in twelve rats (Wistar, male) with weight range 197-242 g. An approximative anastomosis in the ileum of six rats was perf...
Article
Hypoxic pulmonary vasoconstriction (HPV), an important physiological mechanism, is regulated by changes in the production of and interactions among reactive oxygen species (ROS). There is controversy, however, over whether HPV is mediated by an increase or a decrease in ROS production. Also, the role of NO in HPV remains unclear. The aim of this st...
Article
Full-text available
The aim was to determine whether increased oxidative stress during the adaptation to chronic intermittent hypoxia (CIH) plays a role in the induction of improved cardiac ischemic tolerance. Adult male Wistar rats were exposed to CIH in a hypobaric chamber (7,000 m, 8 h/day, 5 days/wk, 24-30 exposures). Half of the animals received antioxidant N-ace...
Article
Full-text available
Chronic hypoxia results in pulmonary hypertension due to vasoconstriction and structural remodelling of peripheral lung blood vessels. We hypothesize that vascular remodelling is initiated in the walls of prealveolar pulmonary arteries by collagenolytic metalloproteinases (MMP) released from activated mast cells. Distribution of mast cells and thei...
Article
Full-text available
Pathogenesis of hypoxic pulmonary hypertension is initiated by oxidative injury to the pulmonary vascular wall. Because nitric oxide (NO) can contribute to oxidative stress and because the inducible isoform of NO synthase (iNOS) is often upregulated in association with tissue injury, we hypothesized that iNOS-derived NO participates in the pulmonar...
Article
Full-text available
Exposure to chronic hypoxia results in hypoxic pulmonary hypertension (HPH). In rats HPH develops during the first two weeks of exposure to hypoxia, then it stabilizes and does not increase in severity. We hypothesize that free radical injury to pulmonary vascular wall is an important mechanism in the early days of the hypoxic exposure. Thus antiox...
Article
The etiology of neuronal intestinal dysplasia remains largely unknown. There is, however, supporting evidence of the existence of Hirschprung's disease or chronic intestinal obstruction associated with neuronal intestinal dysplasia. With the aim of investigating the possible development of neuronal intestinal dysplasia linked to chronic intestinal...
Article
The etiology of neuronal intestinal dysplasia remains largely unknown. There is, however, supporting evidence of the existence of Hirschprung's disease or chronic intestinal obstruction associated with neuronal intestinal dysplasia. With the aim of investigating the possible development of neuronal intestinal dysplasia linked to chronic intestinal...
Article
Full-text available
The ultrastructure of the tracheal epithelium in rabbits exposed for 96 hours to 35-37% O2 was studied in our experiments. Due to the influence of mild normobaric hyperoxia, massive differentiation of new secretory elements was initiated and resulted in apparent changes in goblet cells distribution. 60 ± 4% of goblet cells took part in the formatio...
Article
Full-text available
Some effects of perinatal hypoxia on pulmonary circulation are permanent. Since pulmonary vascular sensitivity to hypoxia in adults differs between sexes, we hypothesized that gender-based variability also exists in the long-term effects of perinatal hypoxia. Rats spent 1 wk before and 1 wk after birth in hypoxia (12% O2) and then lived in normoxia...
Article
Full-text available
Chronic hypoxia induces lung vascular remodeling, which results in pulmonary hypertension. We hypothesized that a previously found increase in collagenolytic activity of matrix metalloproteinases during hypoxia promotes pulmonary vascular remodeling and hypertension. To test this hypothesis, we exposed rats to hypoxia (fraction of inspired oxygen =...
Article
Full-text available
Pathogenesis of pulmonary hypertension includes vascular smooth muscle cell membrane depolarisation and consequent calcium influx. Usually, calcium-gated potassium channels are activated under such conditions and repolarise the membrane. However, in pulmonary hypertension they are downregulated. The authors hypothesised that pharmacological augment...
Article
Full-text available
The effect of chronic hypercapnia on cardioprotection induced by chronic hypoxia was investigated in adult male Wistar rats exposed to isobaric hypoxia (10 % O(2)) for three weeks. In the first experimental group, CO(2) in the chamber was fully absorbed; in the second group, its level was increased to 4.1 %. Normoxic controls were kept in atmospher...
Article
Pathogenesis of pulmonary hypertension includes downregulation of potassium channels. Pharmacological augmentation of these channels thus may be expected to limit the development of pulmonary hypertension. Recently, an endogenous steroid, dehydroepiandrosterone (DHEA), was shown to activate a calcium dependent subfamily of potassium channels in the...
Article
Full-text available
Overdose of tricyclic antidepressants, which inhibit cellular serotonin (5-HT) uptake, sometimes causes acute respiratory syndrome-like symptoms. Their acute and chronic cardiopulmonary actions, which might be implicated, utilising both in vivo and ex vivo animal studies, were investigated in this study. Acute amitriptyline (AMI), iprindole and imi...
Article
Full-text available
e ultrastructure of the tracheal epithelium in rabbits exposed for 96 hours to normobaric hypoxia was studied. In rabbits placed for 96 hours in environment with increased temperature and humidity, the first phase of common response of goblet cells to injury, represented mostly by degeneration of the exhausted cells, was revealed. e decrease in O...
Article
Full-text available
Exposure to chronic hypoxia results in hypoxic pulmonary hypertension characterized by structural remodeling of peripheral pulmonary vasculature. An important part of this remodeling is an increase of collagen turnover and deposition of newly formed collagen fibrils in the vascular walls. The activity of collagenolytic metalloproteinases in the lun...
Article
Full-text available
Systemic and pulmonary hypertension is characterised by structural reconstruction of the vascular wall which includes hypertrophy and hyperplasia of vascular smooth muscle cells (VSMCs) and fibroproduction. We hypothesise that these changes are stimulated by non-enzymatic modification of collagen molecules in the injured vascular wall by radicals....
Article
Full-text available
Chronic hypoxia causes pulmonary hypertension, the mechanism of which includes altered collagen metabolism in the pulmonary vascular wall. This chronic hypoxic pulmonary hypertension is gradually reversible upon reoxygenation. The return to air after the adjustment to chronic hypoxia resembles in some aspects a hyperoxic stimulus and we hypothesize...
Article
Full-text available
Chronic pulmonary hypertension is a serious complication of a number of chronic lung and heart diseases. In addition to vasoconstriction, its pathogenesis includes injury to the peripheral pulmonary arteries leading to their structural remodeling. Increased pulmonary vascular synthesis of an endogenous vasodilator, nitric oxide (NO), opposes excess...
Article
Full-text available
Chronic sojourn in hypoxic environment results in the structural remodeling of peripheral pulmonary arteries and pulmonary hypertension. We hypothesize that the pathogenesis of changes in pulmonary vascular structure is related to the increase of radical production induced by lung tissue hypoxia. Hypoxia primes alveolar macrophages to produce more...
Article
Full-text available
The most dramatic changes in pulmonary circulation occur at the time of birth. We hypothesized that some of the effects of perinatal hypoxia on pulmonary vessels are permanent. We studied the consequences of perinatal exposure to hypoxia (12 % O2 one week before and one week after birth) in isolated lungs of adult male rats (approximately 12 weeks...