Pacienti cévní chirurgie jsou vystaveni riziku tzv. sekundárního traumatu, které vzniká na podkladě patologických změn způsobených nejdříve ischemií a následně reperfuzí. Ischemicko ‐reperfuzní syndrom v důsledku oxidativního stresu a vystupňované buněčné smrti pak podstatnou měrou přispívá k vysoké perioperační morbiditě a mortalitě těchto pacientů. Ve snaze o snížení negativního dopadu těchto procesů, byla vyvinuta řada opatření, k nimž patří i koncept vzdálené ischemické prekondice. S ohledem na analogii mezi patofyziologií ischemické prekondice a poruch dýchání ve spánku můžeme usuzovat na menší dopad ischemicko ‐reperfuzních změn u pacientů s obstrukční spánkovou apnoe.

Vascular surgery patients are exposed to the risk of secondary trauma, which arises on the basis of pathological changes caused first by ischemia and then by reperfusion. Ischemia-reperfusion syndrome due to oxidative stress and increased cell death contributes significantly to the high perioperative morbidity and mortality of these patients. In an attempt to reduce the negative impact of these processes, a number of measures have been developed, including the concept of remote ischemic preconditioning. Based on the analogy between the pathophysiology of ischemic preconditioning and sleep disordered breathing, we can hypothesize a smaller impact of ischemia-reperfusion changes in patients with obstructive sleep apnea.

• MeSH
• anestetika terapeutické užití   MeSH
• farmakoterapie metody   MeSH
• karotická endarterektomie škodlivé účinky   MeSH
• lidé MeSH
• nemoci ledvin etiologie   mortalita   MeSH
• oxidační stres fyziologie   MeSH
• pooperační komplikace etiologie   klasifikace   mortalita   patofyziologie   MeSH
• přivykání k ischémii dějiny   metody   MeSH
• reperfuzní poškození * etiologie   mortalita   patofyziologie   terapie   MeSH
• simendan farmakologie   terapeutické užití   MeSH
• transplantace škodlivé účinky   MeSH
• výkony cévní chirurgie * škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND AND PURPOSE: Ischemia-reperfusion injury is encountered in numerous processes such as cardiovascular diseases or kidney transplantation; however, the latter involves cold ischemia, different from the warm ischemia found in vascular surgery by arterial clamping. The nature and the intensity of the processes induced by ischemia types are different, hence the therapeutic strategy should be adapted. Herein, we investigated the protective role of tannic acid, a natural polyphenol in a rat model reproducing both renal warm ischemia and kidney allotransplantation. The follow-up was done after 1 week. EXPERIMENTAL APPROACH: To characterize the effect of tannic acid, an in vitro model of endothelial cells subjected to hypoxia-reoxygenation was used. KEY RESULTS: Tannic acid statistically improved recovery after warm ischemia but not after cold ischemia. In kidneys biopsies, 3h after warm ischemia-reperfusion, oxidative stress development was limited by tannic acid and the production of reactive oxygen species was inhibited, potentially through Nuclear Factor erythroid-2-Related factor 2 (NRF2) activation. In vitro, tannic acid and its derivatives limited cytotoxicity and the generation of reactive oxygen species. Molecular dynamics simulations showed that tannic acid efficiently interacts with biological membranes, allowing efficient lipid oxidation inhibition. Tannic acid also promoted endothelial cell migration and proliferation during hypoxia. CONCLUSIONS: Tannic acid was able to improve renal recovery after renal warm ischemia with an antioxidant effect putatively extended by the production of its derivatives in the body and promoted cell regeneration during hypoxia. This suggests that the mechanisms induced by warm and cold ischemia are different and require specific therapeutic strategies.

• MeSH
• krysa rodu rattus MeSH
• ledviny * metabolismus   patologie   patofyziologie   MeSH
• modely nemocí na zvířatech MeSH
• obnova funkce účinky léků   MeSH
• reperfuzní poškození * metabolismus   patologie   patofyziologie   MeSH
• taniny farmakologie   MeSH
• vyšetření funkce ledvin MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In this study we tested a hypothesis that reperfusion ventricular tachyarrhythmias can be modified by direct control of repolarization duration in the perfused myocardium during ischemic exposure. After induction of coronary occlusion, three groups of rats were given agencies affecting repolarization duration tetraethylammonium (TEA) 4 mg/kg, n = 9; pinacidil (Pin) 0.3 mg/kg, n = 11, and saline as placebo (control) n = 10. Unipolar electrograms were recorded from ischemic and perfused areas using an array of 64-electrodes to obtain activation times (ATs), repolarization times (RTs), activation-repolarization intervals (ARIs) and dispersion of repolarization (DOR). During ischemia/reperfusion ARIs in perfused area did not change in the control, significantly increased in the TEA and decreased in the Pin group in respect to baseline, whereas ARIs significantly decreased in the ischemic zone in all groups. DOR also significantly increased in all groups at ischemia and reperfusion. The incidence and total arrhythmia score of reperfusion tachyarrhythmias were significantly greater in TEA group compared to Pin and control groups. In multivariate regression analysis, incidence of VT/VFs and total arrhythmia score were associated with ARIs in the perfused area. Thus, the effect on repolarization durations in the perfused area modified the incidence and severity of the reperfusion-induced ventricular tachyarrhythmias.

• MeSH
• akční potenciály fyziologie   MeSH
• elektrokardiografie metody   MeSH
• komorová tachykardie patofyziologie   MeSH
• krysa rodu rattus MeSH
• myokard patologie   MeSH
• potkani Wistar MeSH
• reperfuzní poškození patofyziologie   MeSH
• srdce patofyziologie   MeSH
• srdeční arytmie patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The aim of our study was to analyse the possible protective effect of quercetin application during the jejunal ischemia-reperfusion injury (IRI) in rats. Quercetin was administered intraperitoneally 30min before 1h ischemia of superior mesenteric artery with following 24h lasting reperfusion period. The male specific pathogen-free (SPF) Charles River Wistar rats were used. In the group with applied quercetin, the significantly increased (p<0.001) levels of anti-inflammatory cytokine IL10 were observed both in the blood serum and jejunal tissue. The improvement of the mucosal tissue morphology and proliferating and DNA repairing cell number measured by PCNA activity were recorded by more than 30% higher in the quercetin group. Simultaneously, significant elongation of the intestinal glands (p<0.001) and increase in the number of CD68-positive cells in the lamina propria mucosae (p<0.001) in comparison with control group were found. Based on our results, the preventive application of quercetin before induction of jejunal IRI stimulates faster jejunal mucosa restoration and it seems to have immunomodulatory and anti-inflammatory effects as well. CD68-positive macrophages could have crucial role in this process since they work as both growth factor and cytokine producers.

• MeSH
• antiflogistika farmakologie   MeSH
• antigeny diferenciační myelomonocytární metabolismus   MeSH
• CD antigeny metabolismus   MeSH
• jejunum účinky léků   MeSH
• krysa rodu rattus MeSH
• quercetin farmakologie   MeSH
• reperfuzní poškození patofyziologie   MeSH
• žaludeční sliznice účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Aim of the study was to find out which myocardial repolarization parameters predict reperfusion ventricular tachycardia and fibrillation (VT/VF) and determine how these parameters express in ECG. METHODS: Coronary occlusion and reperfusion (30/30min) was induced in 24 cats. Local activation and end of repolarization times (RT) were measured in 88 intramyocardial leads. Computer simulations of precordial electrograms were performed. RESULTS: Reperfusion VT/VF developed in 10 animals. Arrhythmia-susceptible animals had longer RTs in perfused areas [183(177;202) vs 154(140;170) ms in susceptible and resistant animals, respectively, P<0.05]. In logistic regression analysis, VT/VFs were associated with prolonged RTs in the perfused area (OR 1.068; 95% CI 1.012-1.128; P=0.017). Simulations demonstrated that prolonged repolarization in the perfused/border zone caused precordial terminal T-wave inversion. CONCLUSIONS: The reperfusion VT/VFs were independently predicted by the longer RT in the perfused zone, which was reflected in the terminal negative phase of the electrocardiographic T-wave.

• MeSH
• elektrokardiografie * MeSH
• fibrilace komor patofyziologie   MeSH
• kočky MeSH
• komorová tachykardie patofyziologie   MeSH
• modely nemocí na zvířatech MeSH
• reperfuzní poškození patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• kočky MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• angioplastika balónková laserová metody   MeSH
• cerebrovaskulární poruchy diagnóza   etiologie   MeSH
• kardiopulmonální resuscitace MeSH
• krevní glukóza analýza   MeSH
• lidé MeSH
• prediktivní hodnota testů MeSH
• reperfuzní poškození myokardu etiologie   MeSH
• reperfuzní poškození etiologie   patofyziologie   terapie   MeSH
• terapeutická hypotermie metody   MeSH
• zástava srdce mimo nemocnici * komplikace   terapie   MeSH
• Check Tag
• lidé MeSH

Lifesaving therapy for patients with end-stage lung disease is lung transplantation. However, there are not enough available donors. A relatively new method of transplantation from non-heart-beating donors (NHBDs) allows the treatment of the lung outside the body and could increase the number of suitable lungs. We have focused on hypercapnic ventilation, which has the possibility of reducing reactive oxygen species damage. We used four experimental and two control groups of adult rats. Each experimental group underwent the protocol of NHBD lung harvesting. The lungs were than perfused in an ex vivo model and we measured weight gain, arterial-venous difference in partial pressure of oxygen and perfusion pressure. We observed that hypercapnic ventilation during reperfusion reduces the development of pulmonary oedema and has a protective effect on the oxygen transport ability of the lungs after warm ischemia. The effect of CO2 on pulmonary oedema and on oxygen transport ability after warm ischemia could be of clinical importance for NHBD transplantation.

• MeSH
• hyperkapnie * MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• potkani Wistar MeSH
• reperfuzní poškození patofyziologie   prevence a kontrola   MeSH
• transplantace plic škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The sphingosine-1-phosphate (S1P) receptor modulator, fingolimod (FTY720), has been used for the treatment of patients with relapsing forms of multiple sclerosis, but atrioventricular (AV) conduction block have been reported in some patients after the first dose. The underlying mechanism of this AV node conduction blockade is still not well-understood. In this study, we hypothesize that expression of this particular arrhythmia might be related to a direct effect of FTY720 on AV node rather than a parasympathetic mimetic action. We, therefore, investigated the effect of FTY720 on AV nodal, using in vitro rat model preparation, under both basal as well as ischaemia/reperfusion conditions. We first look at the expression pattern of S1P receptors on the AV node using real-time PCR. Although all three S1P receptor isoforms were expressed in AVN tissues, S1P1 receptor isoform expression level was higher than S1P2 and S1P3. The effect of 25 nM FTY720 on cycle length (CL) was subsequently studied via extracellular potentials recordings. FTY720 caused a mild to moderate prolongation in CL by an average 9% in AVN (n = 10, P < 0.05) preparations. We also show that FTY720 attenuated both ischaemia and reperfusion induced AVN rhythmic disturbance. To our knowledge, these remarkable findings have not been previously reported in the literature, and stress the importance for extensive monitoring period in certain cases, especially in patients taking concurrently AV node blocker agents.

• MeSH
• disekce MeSH
• fingolimod hydrochlorid farmakologie   MeSH
• krysa rodu rattus MeSH
• lysofosfolipidy farmakologie   MeSH
• messenger RNA genetika   metabolismus   MeSH
• nodus atrioventricularis účinky léků   patofyziologie   MeSH
• receptory lysosfingolipidů metabolismus   MeSH
• regulace genové exprese účinky léků   MeSH
• reperfuzní poškození patologie   patofyziologie   MeSH
• sfingosin analogy a deriváty   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Úvod: Při přenosu volných laloků užívaných v plastické a rekonstrukční chirurgii dochází ke střídání ischemie a reperfuze – ischemicko-reperfuzní syndrom (I/R). Cíl: 1. Vytvořit klinicky relevantní experimentální model volného svalového laloku musculus latissimus dorsi (MLD). 2. Vypracovat metodiku, která by pomocí běžných laboratorních postupů detekovala změny vznikající během oxidačního stresu. 3. Zjistit, do jaké míry má ischemie a následná reperfuze vliv na svalovou tkáň volného laloku MLD (z hlediska oxidačního stresu). Metody: U 18 prasat domácích byl oboustranně vypreparován MLD (kontrolní a zkoumaný), jehož výživa byla ponechána pouze na cévní stopce thorakodorzálního svazku. Byl odebrán první kontrolní žilní, arteriální a svalový vzorek. Následně byla cévní stopka zkoumaného MLD dočasně zasvorkována (na 60 minut) – simulace ischemie při odpojení laloku. Po uvolnění svorky – simulace reperfuze po provedení mikroanastomózy – byly v arteriální krvi, žilní krvi a svalu z kontrolního a ischemického laloku v čase těsně před zasvorkováním a dále v 1., 30., 45., 60. minutě reperfuze stanoveny: krevní obraz, laktát, pyruvát, glutathionperoxidáza, glutathion, karbonyl, superoxiddismutáza, TBARS, izoprostany, kreatinkináza, aspartátaminotransferáza, myoglobin, D-dimery, PF4, ICAM-1, VCAM-1. Výsledky: Během experimentu statisticky významně rostla hladina kalia v arteriální krvi (4,08 ± 0,127; 4,35 ± 0,159; 4,67 ± 0,201; 4,79 ± 0,198; 4,86 ± 0,202 mmol/l; p = <0,001) i žilní krvi obou laloků (v-i 4,17 ± 0,108; 4,83 ± 0,229; 6,22 ± 0,513; 5,59 ± 0,189; 5,57 ± 0,221 mmol/l; p = < 0,001), (v-c 4,17 ± 0,108; 4,92 ± 0,214; 5,34 ± 0,251; 5,47 ± 0,276; 5,53 ± 0,244 mmol/l; p = < 0,001). Hladina pyruvátu v arteriální krvi významně klesala (0,363 ± 0,038; 0,231 ± 0,034; 0,188 ± 0,025; 0,216 ± 0,041; 0,176 ± 0,030 mmol/l; p = 0,003), v žilní krvi ischemického laloku významně vzrostla (0,383 ± 0,074; 0,371 ± 0,050; 0,312 ± 0,039; 0,536 ± 0,080; 0,397 ± 0,058 mmol/l; p = 0,002), v krvi kontrolního laloku se neměnila. Hladina laktátu významně klesla na systémové úrovni (8,29 ± 1,200; 5,27 ± 1,074; 5,34 ± 0,978; 5,33 ± 1,006; 5,27 ± 0,875 mmol/l; p = 0,014), na lokální stagnovala. Hodnoty sledovaných parametrů ve svalu a dynamika ostatních sledovaných parametrů v porovnání systémových a lokálních změn se významně nelišily. Závěr: Lokální projevy oxidačního stresu tkáně volného svalového laloku jsou potlačeny v porovnání se systémovými, nejspíše jako projev ochrany navozené předchozí ventilací hyperoxickou směsí.

Introduction: Free muscle flap transfers, frequently used in plastic and reconstructive surgery, are associated with alternating episodes of ischemia and reperfusion, a condition called ischemic-reperfusion injury (I/R). This phenomenon could be a cause of damage in the transferred flap. Major detrimental effects are usually attributed to the oxidative stress. Aim: The aim of this study was therefore 1) to develop a clinically relevant experimental model of free muscle flap for musculus latissimus dorsi (MLD), 2) to elaborate a technique allowing, by means of routine laboratory methods, the detection of changes occurring as a result of oxidative stress, and 3) to evaluate the impact of ischemia and subsequent reperfusion on free flap muscle tissue (in terms of oxidative stress). Methods: In 18 domestic pigs, MLD was prepared on both sides (experimental and control), leaving just the thoracodorsal branch for nutrition. The vascular stalk for the experimental MLD was clamped temporarily (60 min) to mimic ischemia during flap transfer. After the clamp release (corresponds to reperfusion following anastomosis), both arterial, venous blood, and tissue samples were obtained from the ischemic as well as control flaps at time points 1, 30, 45, and 60 min. For baseline characteristics, tissue, arterial, and venous blood were sampled prior to clamping. In all samples, lactate, pyruvate, glutathion peroxidase, glutathion, TBARS, creatinkinase, aspartate aminotransferase, and myoglobin were determined. Results: During the experiment, statistically significant time-dependent changes were observed in potassium levels within arterial blood (4.08±0.127; 4.35±0.159; 4.67±0.201; 4.79±0.198; 4.86±0.202 mmol/l; p<0.001), ischemic flap venous blood (4.17±0.108; 4.83±0.229; 6.22±0.513; 5.59±0.189; 5.57±0.221 mmol/l; p<0.001), and control flap venous blood (4.17±0.108; 4.92±0.214; 5.34±0.251; 5.47±0.276; 5.53±0.244 mmol/l; p<0.001). While arterial blood pyruvate decreased significantly (0.363±0.038; 0.231±0.034; 0.188±0.025; 0.216±0.041; 0.176±0.030 mmol/l; p=0.003), its ischemic flap venous levels raised significantly (0.383±0.074; 0.371±0.050; 0.312±0.039; 0.536±0.080; 0.397±0.058 mmol/l; p=0.002) and control flap venous levels remained unchanged. Systemic lactate was found to decline (8.29±1.200; 5.27±1.074; 5.34±0.978; 5.33±1.006; 5.27±0.875 mmol/l; p=0.014) while venous levels did not differ significantly. The other determined blood and tissue markers did not show significant changes.

• MeSH
• chirurgické laloky krevní zásobení   MeSH
• ischemie MeSH
• mikrochirurgie metody   MeSH
• modely u zvířat * MeSH
• oxidační stres * fyziologie   MeSH
• povrchové zádové svaly chirurgie   krevní zásobení   patofyziologie   MeSH
• prasata fyziologie   chirurgie   krev   MeSH
• reperfuzní poškození * patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

The effect of blocking the first and rate-limiting step in renin-angiotensin cascade on the renal function in ischemia reperfusion injury has not been previously investigated. We investigated the effect of aliskiren, the first approved direct oral renin inhibitor, on the alterations in renal functional parameters in this condition. Wistar rats underwent left renal ischemia for 40 min. Group-1 received normal saline whereas Group-2 received aliskiren (30 mg/kg/day) by gavage for 6 days commencing one day before IRI. The hemodynamic and tubular functions and gene expression of neutrophil gelatinase-associated lipocalin (NGAL) and plasminogen activating inhibitor (PAI-1) in the right and left kidneys were measured five days following the IRI. Comparing Group-1 and Group-2, the left renal blood flow was significantly higher in Group-2 (1.28+/-0.36 vs. 0.39+/-0.05, P=0.007). Left kidney glomerular filtration rate was also higher in Group-2 but did not reach statistical significance (0.18+/-0.05 vs. 0.10+/-0.02, P=0.07). The left renal FE(Na) was significantly lower in Group-2 (29.9+/-6.4 vs. 49.7+/-7.8, P=0.03). Aliskiren also caused a significant decrease in the gene expression of both NGAL and PAI-1 in the left ischemic kidney. In conclusions, the administration of aliskiren before and after IRI appears to have ameliorated the IRI effect on the total renal artery blood flow, fractional excretion of sodium and gene expression of both NGAL and PAI-1 indicating a renoprotective effects in IRI.

• MeSH
• amidy aplikace a dávkování   MeSH
• fumaráty aplikace a dávkování   MeSH
• hodnoty glomerulární filtrace účinky léků   MeSH
• krysa rodu rattus MeSH
• ledvinné látky aplikace a dávkování   MeSH
• ledviny účinky léků   patofyziologie   MeSH
• nemoci ledvin farmakoterapie   patofyziologie   MeSH
• potkani Wistar MeSH
• renální oběh účinky léků   MeSH
• renin-angiotensin systém účinky léků   MeSH
• renin antagonisté a inhibitory   MeSH
• reperfuzní poškození patofyziologie   prevence a kontrola   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH