Pulmonary hypertension is a group of disorders characterized by elevated mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance. To test our hypothesis that combining two drugs useful in experimental pulmonary hypertension, statins and dehydroepiandrosterone sulfate (DHEA S), is more effective than either agent alone, we induced pulmonary hypertension in adult male rats by exposing them to hypoxia (10%O2) for 3 weeks. We treated them with simvastatin (60 mg/l) and DHEA S (100 mg/l) in drinking water, either alone or in combination. Both simvastatin and DHEA S reduced mPAP (froma mean±s.d. of 34.4±4.4 to 27.6±5.9 and 26.7±4.8 mmHg, respectively), yet their combination was not more effective (26.7±7.9 mmHg). Differences in the degree of oxidative stress (indicated by malondialdehydeplasma concentration),the rate of superoxide production (electron paramagnetic resonance), or blood nitric oxide levels (chemiluminescence) did not explain the lack of additivity of the effect of DHEA S and simvastatin on pulmonary hypertension. We propose that the main mechanism of both drugs on pulmonary hypertension could be their inhibitory effect on 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, which could explain their lack of additivity.

• MeSH
• arteria pulmonalis MeSH
• dehydroepiandrosteron farmakologie   terapeutické užití   MeSH
• dehydroepiandrosteronsulfát MeSH
• hypoxie komplikace   farmakoterapie   patologie   MeSH
• krysa rodu rattus MeSH
• plicní hypertenze * farmakoterapie   MeSH
• simvastatin farmakologie   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Cardioprotective effect of ischemic preconditioning (IPC) and ischemic postconditioning (IPoC) in adult hearts is mediated by mitochondrial-K-ATP channels and nitric oxide (NO). During early developmental period, rat hearts exhibit higher resistance to ischemia-reperfusion (I/R) injury and their resistance cannot be further increased by IPC or IPoC. Therefore, we have speculated, whether mechanisms responsible for high resistance of neonatal heart may be similar to those of IPC and IPoC. To test this hypothesis, rat hearts isolated on days 1, 4, 7, and 10 of postnatal life were perfused according to Langendorff. Developed force (DF) of contraction was measured. Hearts were exposed to 40 min of global ischemia followed by reperfusion up to the maximum recovery of DF. IPoC was induced by 5 cycles of 10-s ischemia. Mito-K-ATP blocker (5-HD) was administered 5 min before ischemia and during first 20 min of reperfusion. Another group of hearts was isolated for biochemical analysis of 3-nitrotyrosine, and serum samples were taken to measure nitrate levels. Tolerance to ischemia did not change from day 1 to day 4 but decreased on days 7 and 10. 5-HD had no effect either on neonatal resistance to I/R injury or on cardioprotective effect of IPoC on day 10. Significant difference was found in serum nitrate levels between days 1 and 10 but not in tissue 3-nitrotyrosine content. It can be concluded that while there appears to be significant difference of NO production, mito-K-ATP and ROS probably do not play role in the high neonatal resistance to I/R injury.

• MeSH
• draslíkové kanály metabolismus   MeSH
• ischemický postconditioning * MeSH
• krysa rodu rattus MeSH
• novorozená zvířata MeSH
• oxid dusnatý metabolismus   MeSH
• potkani Wistar MeSH
• reperfuzní poškození myokardu metabolismus   patofyziologie   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

A common problem in management of polytrauma - a simultaneous injury to more than one organ or organ system, at least one of them lethal without intervention - is a discrepancy between a relatively good initial state and a serious subsequent development. Since nitric oxide (NO) is produced in high quantities during tissue injury, we assumed that serum levels of NO (and its oxidation products, NOx) might serve as a prognostic marker of polytrauma severity. However, we found recently that NOx was increased in polytrauma, but not in the most severe cases. The present study was undertaken to test the hypothesis that serum NOx is reduced in severe polytrauma by concomitant overproduction of reactive oxygen species (ROS). Polytrauma was induced in rats under anesthesia by bilateral fracture of femurs and tibiae plus incision of the right liver lobe through laparotomy. Serum NOx was measured by chemiluminescence after hot acidic reduction. The role of ROS was assessed by treatment with an antioxidant, N-acetyl-L-cysteine (NAC). Experimental polytrauma elevated NOx from 11.0+/-0.7 to 23.8+/-4.5 ppb. This was completely prevented by NAC treatment (9.1+/-2.2 ppb). Serum NOx is elevated in severe polytrauma, and this is not reduced by ROS. On the contrary, ROS are necessary for the NOx elevation, probably because ROS produced by inflammatory cells activated by the polytrauma induce massive NO production.

• MeSH
• antioxidancia farmakologie   terapeutické užití   MeSH
• biologické markery krev   MeSH
• krysa rodu rattus MeSH
• oxid dusnatý antagonisté a inhibitory   krev   MeSH
• polytrauma krev   farmakoterapie   MeSH
• potkani Wistar MeSH
• reaktivní formy kyslíku antagonisté a inhibitory   krev   MeSH
• volné radikály antagonisté a inhibitory   krev   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• biologické markery krev   MeSH
• multiorgánové selhání diagnóza   etiologie   MeSH
• oxid dusný * krev   MeSH
• polytrauma * diagnóza   komplikace   krev   patofyziologie   MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• reprodukovatelnost výsledků MeSH
• traumatický šok diagnóza   etiologie   MeSH
• ukazatel závažnosti úrazu MeSH

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. This study investigated the participation of NOS uncoupling in the early phase of hypoxia-induced pulmonary hypertension in rats. Rats were exposed to 10% O(2) for 4 days. We investigated the effect of BH4 in vitro on isolated rat lungs and isolated rat peripheral pulmonary blood vessels and in vivo on exhaled NO concentration in exhaled air. BH4 attenuated hypoxic pulmonary vasoconstriction in isolated lungs and its effect was reversed by l-NAME (NOS inhibitor). The main finding of the study is that the effect of BH4 was smaller in rats exposed to 4 days of hypoxia than in normoxic controls. The finding was similar in isolated pulmonary blood vessels. BH4 increased exhaled NO in both normoxic and hypoxic rats. This increase was blunted by l-NIL (specific iNOS inhibitor) and therefore attributable to iNOS. We conclude that BH4 increased NO production in both normoxic and hypoxic rats. The increase was, however, smaller in hypoxic lungs than in controls. We assume that the smaller increase in NO production in hypoxic lungs is due to the decreased BH4/BH2 ratio in chronic hypoxia and NOS uncoupling resulting from this condition.

• MeSH
• biopteriny analogy a deriváty   metabolismus   MeSH
• hypoxie metabolismus   patofyziologie   MeSH
• krysa rodu rattus MeSH
• oxid dusnatý biosyntéza   MeSH
• plíce metabolismus   patofyziologie   MeSH
• plicní hypertenze metabolismus   patofyziologie   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The aim of the study was to find out whether administration of selenium (Se) will protect the immature heart against ischemia/reperfusion.The control pregnant rats were fed laboratory diet (0.237 mg Se/kg diet); experimental rats received 2 ppm Na(2)SeO(3) in the drinking water from the first day of pregnancy until day 10 post partum. The concentration of Se in the serum and heart tissue was determined by activation analysis, the serum concentration of NO by chemiluminescence, cardiac concentration of lipofuscin-like pigment by fluorescence analysis. The 10 day-old hearts were perfused (Langendorff); recovery of developed force (DF) was measured after 40 min of global ischemia. In acute experiments, 10 day-old hearts were perfused with selenium (75 nmol/l) before or after global ischemia. Sensitivity to isoproterenol (ISO, pD(50)) was assessed as a response of DF to increasing cumulative dose.Se supplementation elevated serum concentration of Se by 16%. Se increased ischemic tolerance (recovery of DF, 32.28 +/- 2.37 vs. 41.82 +/- 2.91%, P < 0.05). Similar results were obtained after acute administration of Se during post-ischemic reperfusion (32.28 +/- 2.37 vs. 49.73 +/- 4.40%, P < 0.01). The pre-ischemic treatment, however, attenuated the recovery (23.08 +/- 3.04 vs. 32.28 +/- 2.37%, P < 0.05). Moreover, Se supplementation increased the sensitivity to the inotropic effect of ISO, decreased cardiac concentration of lipofuscin-like pigment and serum concentration of NO. Our results suggest that Se protects the immature heart against ischemia/reperfusion injury. It seems therefore, that ROS may affect the function of the neonatal heart, similarly as in adults.

• MeSH
• časové faktory MeSH
• financování organizované MeSH
• ischemická choroba srdeční farmakoterapie   prevence a kontrola   MeSH
• kontrakce myokardu účinky léků   MeSH
• krysa rodu rattus MeSH
• lipofuscin metabolismus   MeSH
• oxid dusnatý krev   MeSH
• perfuze MeSH
• potkani Wistar MeSH
• potravní doplňky MeSH
• reperfuzní poškození myokardu farmakoterapie   prevence a kontrola   MeSH
• selen farmakologie   krev   terapeutické užití   MeSH
• srdce účinky léků   MeSH
• těhotenství MeSH
• tělesná hmotnost účinky léků   MeSH
• velikost orgánu účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH

The major goal of this project is to establish proper technique and perform lung transplantation from non-heart-beating-donor on both experimental basis in animals andclinical basis. Introduction of this program could be in some extent crucial contribution to the solution of shortage of organs suitable for lung transplantation.

Tento projekt bude řešit možnost provedení transplantace plic od dárce s nebijícím srdcem v experimentu na zvířatech a v klinické praxi. Zavedení tohoto programu by mohlo výrazně zmírnit dopad nedostatku vhodných orgánů k trasplantaci plic.

• MeSH
• experimenty na lidech MeSH
• randomizované kontrolované studie jako téma MeSH
• srdeční zástava MeSH
• transplantace orgánů trendy   MeSH
• transplantace plic MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• pneumologie a ftizeologie
• transplantologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

BACKGROUND: The aim of this study was to evaluate the influence of oral vitamin E therapy on serum concentrations of several markers of micro-inflammation and cardiovascular disease in chronic hemodialysis (HD) patients. METHODS: 29 HD patients were randomized into two groups: 15 patients were treated orally with 400 mg of vitamin E daily for a period of five weeks, and 14 patients received no antioxidant supplementation. Before and after vitamin E therapy, serum concentrations of vitamin E (high-performance liquid chromatography), pregnancy-associated plasma protein-A (immunochemical--TRACE assay), C-reactive protein (nephelometry), intercellular adhesion molecule-1 (ELISA), and E-selectin (ELISA) were measured. HD patients were compared with 16 healthy controls. RESULTS: Baseline serum concentrations of PAPP-A and CRP were significantly higher in HD patients than in healthy controls (PAPP-A: 26.23+/-11.94 vs. 11.41+/-1.94 mIU/L, p<0.001; CRP: 5.20+/-3.50 vs. 3.40+/-3.80 mg/L, p<0.05). After five weeks of oral vitamin E intake, serum PAPP-A, CRP, ICAM-1, and E-selectin concentrations remained unchanged in both groups of HD patients. CONCLUSION: Chronic micro-inflammation in HD patients is documented by the elevation of CRP and PAPP-A. A daily oral dose of 400 mg of vitamin E does not seem to be able to reduce enhanced oxidative stress and micro-inflammation in chronic HD patients.

• MeSH
• aplikace orální MeSH
• biologické markery krev   MeSH
• C-reaktivní protein analýza   MeSH
• chronické selhání ledvin komplikace   terapie   MeSH
• dialýza ledvin MeSH
• E-selektin krev   MeSH
• financování organizované MeSH
• kardiovaskulární nemoci etiologie   krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezibuněčná adhezivní molekula-1 krev   MeSH
• těhotenský plazmatický protein A analýza   MeSH
• vitamin E aplikace a dávkování   krev   MeSH
• zánět krev   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• randomizované kontrolované studie MeSH

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 pulmonary vascular wall injury at the onset of hypoxic pulmonary hypertension. An effective and selective dose of an iNOS inhibitor, L-N6-(1-iminoethyl)lysine (L-NIL), for chronic peroral treatment was first determined (8 mg/l in drinking water) by measuring exhaled NO concentration and systemic arterial pressure after LPS injection under ketamine+xylazine anesthesia. A separate batch of rats was then exposed to hypoxia (10% O2) and given L-NIL or a nonselective inhibitor of all NO synthases, N(G)-nitro-L-arginine methyl ester (L-NAME, 500 mg/l), in drinking water. Both inhibitors, applied just before and during 1-wk hypoxia, equally reduced pulmonary arterial pressure (PAP) measured under ketamine+xylazine anesthesia. If hypoxia continued for 2 more wk after L-NIL treatment was discontinued, PAP was still lower than in untreated hypoxic controls. Immunostaining of lung vessels showed negligible iNOS presence in control rats, striking iNOS expression after 4 days of hypoxia, and return of iNOS immunostaining toward normally low levels after 20 days of hypoxia. Lung NO production, measured as NO concentration in exhaled air, was markedly elevated as early as on the first day of hypoxia. We conclude that transient iNOS induction in the pulmonary vascular wall at the beginning of chronic hypoxia participates in the pathogenesis of pulmonary hypertension.

• MeSH
• aplikace orální MeSH
• arteria pulmonalis enzymologie   MeSH
• časové faktory MeSH
• chronická nemoc MeSH
• financování organizované MeSH
• hypoxie MeSH
• inhibitory enzymů aplikace a dávkování   farmakologie   MeSH
• krysa rodu rattus MeSH
• lysin aplikace a dávkování   farmakologie   MeSH
• NG-nitroargininmethylester farmakologie   MeSH
• oxid dusnatý MeSH
• plíce metabolismus   MeSH
• plicní hypertenze etiologie   patofyziologie   MeSH
• potkani Wistar MeSH
• synthasa oxidu dusnatého, typ II antagonisté a inhibitory   biosyntéza   MeSH
• vydechnutí MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

• O autorovi
• Herget, Jan, 1945-2019 Autorita

• Publikační typ
• abstrakt z konference MeSH