Inducible NO synthase (NOS II) was proposed to play an important role in salt resistance of Dahl salt-resistant (SR/Jr) rats. Its chronic inhibition by specific inhibitors was accompanied by blood pressure (BP) elevation in animals subjected to high salt intake. The aim of our study was to evaluate 1) whether such inhibitors affect BP and/or its particular components (sympathetic tone and NO-dependent vasodilation) only under the conditions of high salt intake, and 2) whether similar BP effects are elicited after systemic or intracerebroventricular (icv) application of these inhibitors. Wistar rats fed Altromin diet (0.45 % NaCl) and SR/Jr rats fed either a low-salt (LS, 0.3 % NaCl) or a high-salt (HS, 4 % NaCl) diet were studied. Aminoguanidine (AMG) and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT) were used as NOS II inhibitors. BP and its responses to acute blockade of renin-angiotensin system (captopril), sympathetic nervous system (pentolinium) and NO synthase (L-NAME) were measured in conscious cannulated rats. There were no significant changes of BP or its components in either Wistar rats or SR/Jr rats subjected to chronic inhibition of NOS II by peroral aminoguanidine administration (50 mg/kg/day for 4 weeks). This was true for SR/Jr rats fed either LS or HS diets. Furthermore, we have studied BP effects of chronic icv administration of both NOS II inhibitors in SR/Jr rats fed HS diet, but we failed to find any BP changes elicited by such treatment. In conclusion, inducible NO synthase does not participate in the resistance of SR/Jr rats to hypertensive effects of excess salt intake.

• MeSH
• chlorid sodný MeSH
• hypertenze * chemicky indukované   MeSH
• krevní tlak fyziologie   MeSH
• krysa rodu Rattus MeSH
• kuchyňská sůl * MeSH
• oxid dusnatý MeSH
• potkani inbrední Dahl MeSH
• potkani Wistar MeSH
• synthasa oxidu dusnatého, typ II MeSH
• synthasa oxidu dusnatého MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chlorid sodný MeSH
• kuchyňská sůl * MeSH
• oxid dusnatý MeSH
• pimagedine MeSH Prohlížeč
• synthasa oxidu dusnatého, typ II MeSH
• synthasa oxidu dusnatého MeSH

Valsartan has the potential to attenuate neointimal hyperplasia and to suppress the inflammatory response. This study aimed to evaluate the role of valsartan in neointimal hyperplasia and the toll-like receptor 4 (TLR4)-nitric oxide synthase (NOS) pathway in the balloon-injured rat aorta.Forty-eight Wistar rats were randomly allocated to three groups: sham control (control), balloon-injured group (surgery), and balloon-injured+valsartan-treated group (valsartan). Rats were killed at 14 and 28 days after balloon-injury, and then the aortic tissues were collected for morphometric analysis as well as for measurements of the mRNA or protein expression of angiotensin II, angiotensin II type 1 (AT1) receptor, angiotensin II type 2 (AT2) receptor, TLR4, endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), serine/arginine-rich splicing factor 1(SRSF1) and extracellular signal regulated kinase (ERK). Valsartan at a dose of 20 mg/kg/day markedly decreased neointimal hyperplasia in the aorta of balloon-injured rats, and significantly reduced the mRNA or protein expression of TLR4, AT1 receptor, SRSF1 and phosphorylated-ERK (p-ERK) as well as the aortic levels of iNOS (all p < 0.05). Moreover, valsartan increased the eNOS level and AT2 receptor mRNA and protein expression levels (all p < 0.05). Valsartan prevented neointimal hyperplasia and inhibited SRSF1 expression and the TLR4-iNOS-ERK-AT1 receptor pathway in the balloon-injured rat aorta.

• MeSH
• aorta účinky léků   enzymologie   patologie   MeSH
• blokátory receptoru 1 pro angiotenzin II farmakologie   MeSH
• extracelulárním signálem regulované MAP kinasy metabolismus   MeSH
• fosforylace MeSH
• hyperplazie MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• nemoci aorty farmakoterapie   enzymologie   genetika   patologie   MeSH
• neointima * MeSH
• poranění cév farmakoterapie   enzymologie   genetika   patologie   MeSH
• potkani Wistar MeSH
• receptor angiotensinu typ 1 genetika   metabolismus   MeSH
• serin-arginin sestřihové faktory metabolismus   MeSH
• signální transdukce MeSH
• synthasa oxidu dusnatého, typ II metabolismus   MeSH
• toll-like receptor 4 genetika   metabolismus   MeSH
• valsartan farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• blokátory receptoru 1 pro angiotenzin II MeSH
• extracelulárním signálem regulované MAP kinasy MeSH
• Nos2 protein, rat MeSH Prohlížeč
• receptor angiotensinu typ 1 MeSH
• serin-arginin sestřihové faktory MeSH
• SRSF1 protein, rat MeSH Prohlížeč
• synthasa oxidu dusnatého, typ II MeSH
• Tlr4 protein, rat MeSH Prohlížeč
• toll-like receptor 4 MeSH
• valsartan MeSH

Pulmonary arterial hypertension (PAH) isa fatal disease characterized by vascular remodeling and chronic inflammation. Macrophages are the key orchestrators of inflammatory and repair responses, and have been demonstrated to be vital in the pathogenesis of PAH. However, specific phenotype of macrophage polarization (M1 & M2 macrophage) in the development of PAH and the underlying mechanisms how they work are still largely unclear. A rat model of monocrotaline (MCT) induced PAH was used. Hemodynamic analysis and histopathological experiments were conducted at day 3, 7, 14, 21 and 28, respectively. In PAH rat lung tissue, confocal microscopic images showed that CD68+NOS2+ M1-like macrophages were remarkably infiltrated on early stage, but dramatically decreased in mid-late stage. Meanwhile, CD68+CD206+ M2-like macrophages in lung tissue accumulated gradually since day 7 to day 28, and the relative ratio of M2/M1 macrophage increased over time. Results detected by western blot and immunohistochemistry were consistent. Further vitro functional studies revealed the possible mechanism involved in this pathophysiological process. By using Transwell co-culture system, it was found that M1 macrophages inducedendothelial cellapoptosis, while M2 macrophages significantly promoted proliferation of both endothelial cell and smooth muscle cell.These data preliminarily demonstrated a temporal dynamic change of macrophage M1/M2 polarization status in the development of experimental PAH. M1 macrophages participated in the initial stage of inflammation by accelerating apoptosis of endothelial cell, while M2 macrophages predominated in the reparative stage of inflammation and the followed stage of aberrant tissue remodeling.

• MeSH
• antigeny diferenciační myelomonocytární metabolismus   MeSH
• apoptóza MeSH
• arteria pulmonalis metabolismus   patologie   MeSH
• časové faktory MeSH
• CD antigeny metabolismus   MeSH
• cytokiny metabolismus   MeSH
• endoteliální buňky pupečníkové žíly (lidské) metabolismus   patologie   MeSH
• fenotyp MeSH
• kokultivační techniky MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• lidé MeSH
• makrofágy metabolismus   patologie   MeSH
• mediátory zánětu metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• monokrotalin MeSH
• myocyty hladké svaloviny metabolismus   patologie   MeSH
• plicní arteriální hypertenze chemicky indukované   metabolismus   patologie   MeSH
• potkani Sprague-Dawley MeSH
• proliferace buněk MeSH
• receptor mannózy metabolismus   MeSH
• remodelace cév * MeSH
• synthasa oxidu dusnatého, typ II metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny diferenciační myelomonocytární MeSH
• CD antigeny MeSH
• CD68 protein, rat MeSH Prohlížeč
• cytokiny MeSH
• mediátory zánětu MeSH
• monokrotalin MeSH
• Nos2 protein, rat MeSH Prohlížeč
• receptor mannózy MeSH
• synthasa oxidu dusnatého, typ II MeSH

In order to reduce tissue damage caused by ischemia-reperfusion injury, this study aims to investigate the protective effect and mechanism of ?-lipoic acid on hepatic ischemia-reperfusion injury in rats. The bloodstream of rats was blocked in the left middle and left lateral liver lobes of the liver. Forty rats were randomly divided into two groups: treatment group and injury group. Rats were injected with either 25 mg/1 ml of alpha-lipoic acid (treatment group) or 1 ml of saline (injury group) into the caudal vein 15 min before hepatic ischemia-reperfusion. Rat serum alanine aminotransferase (GPT), glutathione (GSH) and superoxide dismutase (SOD) levels were examined at various time points (1, 3, 6 and 12 h) in both groups. Changes in nuclear factor kappa B P65 (NF-kappaB P65) expression in ischemia-reperfusion liver at various time points after reperfusion (1, 3, 6 and 12 h) were evaluated through immunohistochemistry assay. Changes in macrophage inflammatory protein-2 (MIP-2) mRNA and inducible nitric oxide synthase (iNOS) mRNA expression in ischemic reperfused rat livers were detected by RT-PCR. Serum GPT level was significantly higher in the injury group than in the treatment group (P<0.01). NF-kappaB P65, MIP-2 mRNA and iNOS mRNA expression in ischemic reperfused rat livers were significantly higher in the injury group than in the treatment group (P<0.01). Serum GSH and SOD levels were higher in the treatment group than in the injury group (P<0.01). Alpha-lipoic acid significantly reduced ischemia-reperfusion injury in rat livers. This may be associated to the direct scavenging of oxygen-free radicals, increased GSH production, and the activation of downstream media due to decreased NF-kappaB and GSH consumption.

• MeSH
• chemokin CXCL2 genetika   metabolismus   MeSH
• cytoprotekce MeSH
• glutathion metabolismus   MeSH
• játra krevní zásobení   účinky léků   metabolismus   patologie   MeSH
• kyselina lipoová farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• nemoci jater genetika   metabolismus   patologie   prevence a kontrola   MeSH
• oxidační stres účinky léků   MeSH
• potkani Wistar MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• reperfuzní poškození genetika   metabolismus   patologie   prevence a kontrola   MeSH
• scavengery volných radikálů farmakologie   MeSH
• signální transdukce MeSH
• superoxiddismutasa metabolismus   MeSH
• synthasa oxidu dusnatého, typ II genetika   metabolismus   MeSH
• transkripční faktor RelA genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chemokin CXCL2 MeSH
• Cxcl2 protein, rat MeSH Prohlížeč
• glutathion MeSH
• kyselina lipoová MeSH
• Nos2 protein, rat MeSH Prohlížeč
• reaktivní formy kyslíku MeSH
• Rela protein, rat MeSH Prohlížeč
• scavengery volných radikálů MeSH
• superoxiddismutasa MeSH
• synthasa oxidu dusnatého, typ II MeSH
• transkripční faktor RelA MeSH

Our previous research revealed that trehalose, a nonreducing disaccharide of glucose and an important stress responsive factor, proved to have anti-inflammatory, antiapoptotic, and particularly antioxidant properties in UVB-irradiated corneas. Trehalose reduced oxidative stress in corneas induced by UVB irradiation, by means of a decrease in the antioxidant/prooxidant imbalance in the corneal epithelium. In this study, we demonstrate that trehalose of 3% or 6% concentration in eye drops directly decreases oxidative stress in UVB-irradiated corneas, by removing the excessive amount of reactive oxygen species (ROS). Trehalose drops applied on corneas during UVB irradiation once daily for four days resulted in a reduction or even absence of the oxidative stress, DNA damage, and peroxynitrite formation (detected by nitrotyrosine residues), seen in buffer-treated corneas. Furthermore, trehalose treatment applied curatively after repeated irradiation for the subsequent fourteen days led to the renewal of corneal transparency and significant suppression or even absence of neovascularization. This was in contrast to buffer-treated irradiated corneas, where the intracorneal inflammation was developed and the untransparent corneas were vascularized. In conclusion, the treatment of UVB-irradiated corneas with trehalose eye drops removed the excessive amount of ROS in the corneal epithelium, leading to the suppression of oxidative stress and favorable corneal healing. The 6% trehalose showed a higher intensive antioxidant effect.

• MeSH
• hojení ran účinky léků   účinky záření   MeSH
• interleukin-1beta metabolismus   MeSH
• keratiny metabolismus   MeSH
• králíci MeSH
• oxidační stres * účinky léků   účinky záření   MeSH
• poranění rohovky farmakoterapie   MeSH
• poškození DNA MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• reepitalizace účinky léků   účinky záření   MeSH
• rohovka účinky léků   patologie   účinky záření   MeSH
• synthasa oxidu dusnatého, typ II metabolismus   MeSH
• trehalosa farmakologie   terapeutické užití   MeSH
• tyrosin analogy a deriváty   metabolismus   MeSH
• ultrafialové záření * MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• publikace stažené z tisku MeSH
• Názvy látek
• 3-nitrotyrosine MeSH Prohlížeč
• interleukin-1beta MeSH
• keratiny MeSH
• reaktivní formy kyslíku MeSH
• synthasa oxidu dusnatého, typ II MeSH
• trehalosa MeSH
• tyrosin MeSH
• vaskulární endoteliální růstový faktor A MeSH

Currently, there is no satisfactory treatment modality available for cutaneous leishmaniasis (CL). The major objective of the present study was to explore the effect of immunomodulator-levamisole in combination with Glucantime in end-stage unresponsive patients with anthroponotic CL (ACL). Twenty end-stage unresponsive patients with ACL were identified for participation in this single-group trial study. Simultaneously, each patient was received a combination of levamisole pills along with Glucantime during the remedy course. Several in vitro complementary experiments were performed to evaluate the mode of action of levamisole and Glucantime alone and in combination using a macrophage model, in vitro MTT assay, flow cytometry and quantitative real time PCR (qPCR). Overall, 75% of the patients showed complete clinical cure, 10% partially improved and the remaining (15%) had underlying chronic diseases demonstrated no response to the treatment regimen. In in vitro studies, there was no cytotoxic effect associated with these drugs in the range of our experiments. The findings by the flow cytometric analysis represented that the highest apoptotic values corresponded to the drugs combination (32.23%) at 200 μg/ml concentration. Finally, the gene expression level of IL-12 p40, iNOS and TNF-α promoted while the level of IL-10 and TGF-β genes reduced as anticipated. The findings clearly indicated that the combination of levamisole and Glucantime should be considered in end-stage unresponsive patients with ACL who have not responded to basic treatments. The immunomodulatory role of levamisole in mounting immune system as documented by the in vitro experiments and further substantiated by this single-group trail study was highlighted.

• Klíčová slova
• Cutaneous leishmaniasis, End-stage patients, Glucantime, Levamisole, Treatment,
• MeSH
• antiprotozoální látky farmakologie   terapeutické užití   MeSH
• buněčné linie účinky léků   MeSH
• chronická nemoc terapie   MeSH
• dítě MeSH
• dospělí MeSH
• fixní kombinace léků MeSH
• interleukin-10 metabolismus   MeSH
• interleukin-12 - podjednotka p40 metabolismus   MeSH
• kombinovaná farmakoterapie MeSH
• Leishmania tropica účinky léků   patogenita   MeSH
• leishmanióza kožní farmakoterapie   MeSH
• levamisol aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágy účinky léků   MeSH
• meglumin antimoniát aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• myši MeSH
• senioři MeSH
• synthasa oxidu dusnatého, typ II metabolismus   MeSH
• TNF-alfa metabolismus   MeSH
• transformující růstový faktor beta metabolismus   MeSH
• viabilita buněk účinky léků   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• myši MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiprotozoální látky MeSH
• fixní kombinace léků MeSH
• IL10 protein, human MeSH Prohlížeč
• interleukin-10 MeSH
• interleukin-12 - podjednotka p40 MeSH
• levamisol MeSH
• meglumin antimoniát MeSH
• NOS2 protein, human MeSH Prohlížeč
• synthasa oxidu dusnatého, typ II MeSH
• TNF-alfa MeSH
• transformující růstový faktor beta MeSH

Recent data on Duchenne muscular dystrophy (DMD) show myocyte progenitor's involvement in the disease pathology often leading to the DMD patient's death. The molecular mechanism underlying stem cell impairment in DMD has not been described. We created dystrophin-deficient human pluripotent stem cell (hPSC) lines by reprogramming cells from two DMD patients, and also by introducing dystrophin mutation into human embryonic stem cells via CRISPR/Cas9. While dystrophin is expressed in healthy hPSC, its deficiency in DMD hPSC lines induces the release of reactive oxygen species (ROS) through dysregulated activity of all three isoforms of nitric oxide synthase (further abrev. as, NOS). NOS-induced ROS release leads to DNA damage and genomic instability in DMD hPSC. We were able to reduce both the ROS release as well as DNA damage to the level of wild-type hPSC by inhibiting NOS activity.

• Klíčová slova
• DMD, NO synthases, ROS, dystrophin, genome stability, pluripotent stem cells,
• MeSH
• buněčné linie MeSH
• Duchennova muskulární dystrofie genetika   MeSH
• dystrofin nedostatek   genetika   MeSH
• indukované pluripotentní kmenové buňky metabolismus   patologie   MeSH
• lidé MeSH
• nestabilita genomu * MeSH
• oxidační stres MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• synthasa oxidu dusnatého, typ I metabolismus   MeSH
• synthasa oxidu dusnatého, typ II metabolismus   MeSH
• synthasa oxidu dusnatého, typ III metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dystrofin MeSH
• NOS1 protein, human MeSH Prohlížeč
• NOS2 protein, human MeSH Prohlížeč
• NOS3 protein, human MeSH Prohlížeč
• reaktivní formy kyslíku MeSH
• synthasa oxidu dusnatého, typ I MeSH
• synthasa oxidu dusnatého, typ II MeSH
• synthasa oxidu dusnatého, typ III MeSH

Arterial hypertension is a leader among the most common chronic cardiovascular diseases which covers 30-45% of world population with a dynamics of further growth. 1,3-oxazole-4-yl-phosphonic acid derivative (abbreviated as oxazole derivative) is a novel original compound with vasodilating activity. The purpose of this work was to study the NO-mediated mechanism of vasodilating effect of this derivative according to the activity of eNOS, iNOS and NO2- through their content in rats on a resistant arterial hypertension model. The oxazole derivative intraperitoneally administered at a dose of 25 mg/kg prevented development of arterial hypertension by promotion of recovery of eNOS, iNOS and NO2- activity in the studied aorta, heart, and blood serum to the normal level recorded in intact animals. It can be concluded that the mechanism of antihypertensive action of the oxazole derivative is mediated by the NO system. Key words: arterial hypertension nitric oxide 1,3-oxazole-4-yl-phosphonic acid derivative.

• Klíčová slova
• 3-oxazole-4-yl-phosphonic acid derivative, arterial hypertension nitric oxide 1,
• MeSH
• hypertenze farmakoterapie   MeSH
• krevní tlak MeSH
• krysa rodu Rattus MeSH
• kyseliny fosforité farmakologie   MeSH
• oxazoly farmakologie   MeSH
• oxid dusnatý metabolismus   MeSH
• synthasa oxidu dusnatého, typ II metabolismus   MeSH
• synthasa oxidu dusnatého, typ III metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kyseliny fosforité MeSH
• Nos2 protein, rat MeSH Prohlížeč
• Nos3 protein, rat MeSH Prohlížeč
• oxazoly MeSH
• oxid dusnatý MeSH
• synthasa oxidu dusnatého, typ II MeSH
• synthasa oxidu dusnatého, typ III MeSH

Nitric oxide (NO) is a major gasotransmitter involved in several physiological processes of male reproduction. There is, nevertheless, little information concerning the role of NO during semen storage. The aim of this study was to evaluate the effect of NO on boar semen stored at 17oC for 72 h. For this purporse, sperm samples were treated with 0.625, 1.25, 2.5, 5, and 10 mM aminoguanidine (AG) or Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME), a selective and non-selective NO synthase (NOS) inhibitor, respectively. Moreover, sodium nitroprusside (SNP), a NO donor, was used at the dose of 18.75, 37.5, 75, and 150 μM. Sperm motility, membrane integrity, and acrosomal status were evaluated at 0, 4, 24, 48, and 72 h of semen storage. A significant increase of the amplitude of lateral sperm head displacement (ALH), and both curvilinear and straight-line velocity (VCL and VSL, respectively) was observed at 72 h of semen storage in samples treated with 0.625 mM AG, probably because of the antioxidant properties of this NOS inhibitor. Contrarily, 0.625 mM L-NAME showed no effect on boar sperm parameters during the entire period of semen storage. Moreover, AG and L-NAME at 10 mM negatively affected sperm kinetics and acrosome integrity, which may provide further support to the notion that low NO levels are necessary for a normal sperm function. The concentrations of SNP used in this study had mostly no or negative effects on boar sperm parameters during semen storage. In conclusion, the results from this study increase the understanding of the role of NO on boar sperm physiology.

• Klíčová slova
• NO donor, NOS inhibitor, boar spermatozoa, nitric oxide, nitric oxide synthases,
• MeSH
• akrozom účinky léků   MeSH
• buněčná membrána účinky léků   MeSH
• časové faktory MeSH
• guanidiny farmakologie   MeSH
• motilita spermií účinky léků   MeSH
• nitroprusid farmakologie   MeSH
• oxid dusnatý aplikace a dávkování   farmakologie   MeSH
• prasata * MeSH
• spermie účinky léků   MeSH
• synthasa oxidu dusnatého, typ II antagonisté a inhibitory   metabolismus   MeSH
• uchování spermatu veterinární   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• guanidiny MeSH
• nitroprusid MeSH
• oxid dusnatý MeSH
• pimagedine MeSH Prohlížeč
• synthasa oxidu dusnatého, typ II MeSH

We previously demonstrated beneficial effects of 22 h of hyperoxia following near-lethal porcine hemorrhagic shock, whereas therapeutic hypothermia was detrimental. Therefore, we investigated whether shorter exposure to hyperoxia (12 h) would still improve organ function, and whether 12 h of hypothermia with subsequent rewarming could avoid deleterious effects after less severe hemorrhagic shock.Twenty-seven anesthetized and surgically instrumented pigs underwent 3 h of hemorrhagic shock by removal of 30% of the blood volume and titration of the mean arterial blood pressure (MAP) to 40 mm Hg. Post-shock, pigs were randomly assigned to control, hyperoxia (FIO2 100% for 12 h) or hypothermia group (34°C core temperature for 12 h with subsequent rewarming). Before, at the end of shock, after 12 and 23 h of resuscitation, data sets comprising hemodynamics, blood gases, and parameters of inflammation and organ function were acquired. Postmortem, kidney samples were collected for immunohistochemistry and western blotting.Hyperoxia exerted neither beneficial nor detrimental effects. In contrast, mortality in the hypothermia group was significantly higher compared with controls (67% vs. 11%). Hypothermia impaired circulation (MAP 64 (57;89) mm Hg vs. 104 (98; 114) mm Hg) resulting in metabolic acidosis (lactate 11.0 (6.6;13.6) mmol L vs. 1.0 (0.8;1.5) mmol L) and reduced creatinine clearance (26 (9;61) mL min vs. 77 (52;80) mL min) compared to the control group after 12 h of resuscitation. Impaired kidney function coincided with increased renal 3-nitrotyrosine formation and extravascular albumin accumulation.In conclusion, hyperoxia proved to be safe during resuscitation from hemorrhagic shock. The lacking organ-protective effects of hyperoxia compared to resuscitation from near-lethal hemorrhage suggest a dependence of the effectiveness of hyperoxia from shock severity. In line with our previous report, therapeutic hypothermia (and rewarming) was confirmed to be detrimental most likely due to vascular barrier dysfunction.

• MeSH
• analýza krevních plynů MeSH
• hemodynamika fyziologie   MeSH
• hemoragický šok metabolismus   terapie   MeSH
• hyperoxie metabolismus   terapie   MeSH
• oxidační stres fyziologie   MeSH
• prasata MeSH
• synthasa oxidu dusnatého, typ II metabolismus   MeSH
• terapeutická hypotermie MeSH
• tyrosin analogy a deriváty   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3-nitrotyrosine MeSH Prohlížeč
• synthasa oxidu dusnatého, typ II MeSH
• tyrosin MeSH