The cardioprotective effect of ischemic preconditioning (IPC) and ischemic postconditioning (IPoC) in adult hearts is mediated by nitric oxide (NO). During the early developmental period, rat hearts exhibit higher resistance to ischemia-reperfusion (I/R) injury, contain higher levels of serum nitrates, and their resistance cannot be further increased by IPC or IPoC. NOS blocker (L-NAME) lowers their high resistance. Wistar rat hearts (postnatal Days 1 and 10) were perfused according to Langendorff and exposed to 40 min of global ischemia followed by reperfusion with or without IPoC. NO and reactive oxygen species donors (DEA-NONO, SIN-1) and L-NAME were administered. Tolerance to ischemia decreased between Days 1 and 10. DEA-NONO (low concentrations) significantly increased tolerance to I/R injury on both Days 1 and 10. SIN-1 increased tolerance to I/R injury on Day 10, but not on Day 1. L-NAME significantly reduced resistance to I/R injury on Day 1, but actually increased resistance to I/R injury on Day 10. Cardioprotection by IPoC on Day 10 was not affected by either NO donors or L-NAME. It can be concluded that resistance of the neonatal heart to I/R injury is NO dependent, but unlike in adult hearts, cardioprotective interventions, such as IPoC, are most likely NO independent.

• MeSH
• donory oxidu dusnatého farmakologie   MeSH
• ischemické přivykání metody   MeSH
• ischemický postconditioning * metody   MeSH
• krysa rodu rattus MeSH
• molsidomin farmakologie   analogy a deriváty   MeSH
• myokard metabolismus   MeSH
• NG-nitroargininmethylester * farmakologie   MeSH
• novorozená zvířata * MeSH
• oxid dusnatý * metabolismus   MeSH
• potkani Wistar * MeSH
• reperfuzní poškození myokardu * prevence a kontrola   metabolismus   MeSH
• srdce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE OF THE STUDY The purpose of this study was to minimize tourniquet-induced ischemia-reperfusion injury (IRI) in total knee arthroplasty (TKA) surgery using the remote ischemic preconditioning (RIPC) model, as well as to assess antioxidant balance with thioldisulfi de homeostasis (TDH). The secondary goal is to evaluate the impact of RIPC on TKA clinical outcomes. MATERIAL AND METHODS Patients in the ASA I-III group who underwent elective TKA were enrolled in this prospective, randomized, double-blind clinical research. TDH parameters were measured individually in groups with (Group I) and without (Group K) RIPC at the following times: preoperative (T0), right before the pneumatic tourniquet was opened (T1), 1 (T2), 6 (T3), and 24 (T4) hours after it was opened. In addition, at 3-hour intervals, the postoperative pain level was assessed using a visual analog scale (VAS). RESULTS This study included 60 cases (Group K; n=30, Group I; n=30). Both groups had equal native thiol, total thiol, disulfi de levels, disulfi de/native thiol, disulfi de/total thiol, and native thiol/total thiol ratios (p>0.05 for each). The change in native thiol, total thiol, and disulfi de values at T0 and T4 periods, however, was not statistically signifi cant for Group K (p=0.049, p=0.047, p=0.037, and p=0.217, p=0.191, p=0.220, respectively). At the 15th hour, VAS values in group I were considerably lower than in Group K (p=0.002). DISCUSSION This prospective, randomized, controlled trial examined how RIPC affected tourniquet-induced IRI-induced oxidative stress in TKA surgery. Lower native, total, and disulfi de levels at each postoperative time point were signifi cant. RIPC may reduce tourniquet-induced IRI-induced oxidative stress and TDH in TKA surgery. RIPC also reduced postoperative discomfort. CONCLUSIONS Our fi ndings suggest that RIPC may protect against the oxidative stress caused by IRI during limb surgery with a tourniquet and improve postoperative clinical outcomes. Key words: remote ischemic preconditioning, ischemia-reperfusion injury, thiol-disulfi de balance, oxidative stress, total knee arthroplasty.

• MeSH
• dvojitá slepá metoda MeSH
• lidé MeSH
• přivykání k ischémii * metody   MeSH
• prospektivní studie MeSH
• reperfuzní poškození * etiologie   prevence a kontrola   MeSH
• totální endoprotéza kolene * škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

Iron is an essential mineral participating in numerous biological processes in the organism under physiological conditions. However, it may be also involved in the pathological mechanisms activated in various cardiovascular diseases including myocardial ischemia/reperfusion (I/R) injury, due to its involvement in reactive oxygen species (ROS) production. Furthermore, iron has been reported to participate in the mechanisms of iron-dependent cell death defined as "ferroptosis". On the other hand, iron may be also involved in the adaptive processes of ischemic preconditioning (IPC). This study aimed to elucidate whether small amounts of iron may modify the cardiac response to I/R in isolated perfused rat hearts and their protection by IPC. Pretreatment of the hearts with iron nanoparticles 15 min prior to sustained ischemia (iron preconditioning, Fe-PC) did not attenuate post-I/R contractile dysfunction. Recovery of left ventricular developed pressure (LVDP) was significantly improved only in the group with combined pretreatment with iron and IPC. Similarly, the rates of contraction and relaxation [+/-(dP/dt)max] were almost completely restored in the group preconditioned with a combination of iron and IPC but not with iron alone. In addition, the severity of reperfusion arrhythmias was reduced only in the iron+IPC group. No changes in protein levels of "survival" kinases of the RISK pathway (Reperfusion Injury Salvage Kinase) were found except for reduced caspase 3 levels in both preconditioned groups. The results indicate that a failure to precondition rat hearts with iron may be associated with the absent upregulation of RISK proteins and the pro-ferroptotic effect manifested by reduced glutathione peroxidase 4 (GPX4) levels. However, combination with IPC suppressed the negative effects of iron resulting in cardioprotection.

• MeSH
• ischemické přivykání * MeSH
• krysa rodu rattus MeSH
• myokard metabolismus   MeSH
• potkani Wistar MeSH
• přivykání k ischémii * metody   MeSH
• reperfuzní poškození myokardu * metabolismus   MeSH
• srdce MeSH
• železo metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

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

Aging attenuates cardiac tolerance to ischemia/reperfusion (I/R) associated with defects in protective cell signaling, however, the onset of this phenotype has not been completely investigated. This study aimed to compare changes in response to I/R and the effects of remote ischemic preconditioning (RIPC) in the hearts of younger adult (3 months) and mature adult (6 months) male Wistar rats, with changes in selected proteins of protective signaling. Langendorff-perfused hearts were exposed to 30 min I/120 min R without or with prior three cycles of RIPC (pressure cuff inflation/deflation on the hind limb). Infarct size (IS), incidence of ventricular arrhythmias and recovery of contractile function (LVDP) served as the end points. In both age groups, left ventricular tissue samples were collected prior to ischemia (baseline) and after I/R, in non-RIPC controls and in RIPC groups to detect selected pro-survival proteins (Western blot). Maturation did not affect post-ischemic recovery of heart function (Left Ventricular Developed Pressure, LVDP), however, it increased IS and arrhythmogenesis accompanied by decreased levels and activity of several pro-survival proteins and by higher levels of pro-apoptotic proteins in the hearts of elder animals. RIPC reduced the occurrence of reperfusion-induced ventricular arrhythmias, IS and contractile dysfunction in younger animals, and this was preserved in the mature adults. RIPC did not increase phosphorylated protein kinase B (p-Akt)/total Akt ratio, endothelial nitric oxide synthase (eNOS) and protein kinase Cε (PKCε) prior to ischemia but only after I/R, while phosphorylated glycogen synthase kinase-3β (GSK3β) was increased (inactivated) before and after ischemia in both age groups coupled with decreased levels of pro-apoptotic markers. We assume that resistance of rat heart to I/R injury starts to already decline during maturation, and that RIPC may represent a clinically relevant cardioprotective intervention in the elder population.

• MeSH
• fosforylace MeSH
• GSK3B genetika   metabolismus   MeSH
• hemodynamika MeSH
• ischemické přivykání * MeSH
• krysa rodu rattus MeSH
• myokard metabolismus   MeSH
• potkani Wistar MeSH
• proteinkinasa C-epsilon genetika   metabolismus   MeSH
• protoonkogenní proteiny c-akt genetika   metabolismus   MeSH
• reperfuzní poškození myokardu metabolismus   patologie   MeSH
• stárnutí MeSH
• synthasa oxidu dusnatého, typ III genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Application of knowledge about ischemic tolerance to clinic requires the solid understanding of mechanism of creation of this phenomenon. This review summarizes research that has been carried out in many laboratories over a long period of time, but the main focus will be on own experimental research. The main emphasis is devoted to the possibility of preparing full tolerance in the donor's body and its transfer to the patient in the form of activated blood plasma. Such plasma could be administered as soon as the patient is transported to the hospital and would take effect immediately after administration to the patient's bloodstream. One chapter is also devoted to anticonditioning, i.e. the possibility of preventing the activation of tolerance. Anticonditioning could be used to treat oncologic patients. We expect that this method could increase effectiveness of cancer treatment. Cross-tolerance with a wide range of diverse stressors gives us the courage to assume that activated plasma can significantly help with a wide range of pathological events.

• MeSH
• fyziologický stres * MeSH
• ischemický postconditioning * MeSH
• lidé MeSH
• přivykání k ischémii * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Background Stomach preparation by ischaemic conditioning prior to oesophageal resection represents a potential method of reducing the risk of anastomotic complications. This study compares the results of the anastomotic complications of cervical anastomosis after oesophagectomy with a short interval after ischaemic conditioning (group S) and a long interval (group L). Methods Subjects undergoing oesophagectomy for carcinoma after ischaemic conditioning were divided into two groups. Group S had a median interval between ischaemic conditioning and resection of 20 days, while for group L the median interval was 49 days. Anastomotic leak and anastomotic stenosis in relation to the interval between ischaemic conditioning and actual resection were followed. Results After ischaemic conditioning, 33 subjects in total underwent surgery for carcinoma; 19 subjects in group S and 14 subjects in group L. Anastomotic leak incidence was comparable in both groups. Anastomotic stenosis occurred in 21% of cases in group S and 7% of cases in group L (not statistically significant). Conclusions A long interval between ischaemic conditioning and oesophagectomy does not adversely affect the postoperative complications. A lower incidence of anastomosis stenoses was found in subjects with a longer interval, however, given the size of our sample, the statistical significance was not demonstrated. Both groups seem comparable in surgical procedure course and postoperative complications.

• MeSH
• anastomóza chirurgická škodlivé účinky   metody   MeSH
• časové faktory MeSH
• dospělí MeSH
• ezofagektomie škodlivé účinky   MeSH
• incidence MeSH
• lidé středního věku MeSH
• lidé MeSH
• miniinvazivní chirurgické výkony škodlivé účinky   metody   MeSH
• nádory jícnu chirurgie   MeSH
• netěsnost anastomózy epidemiologie   etiologie   MeSH
• přivykání k ischémii škodlivé účinky   metody   MeSH
• senioři MeSH
• stenóza epidemiologie   etiologie   MeSH
• žaludek chirurgie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

Currently, there are no satisfactory interventions to protect the heart against the detrimental effects of ischemia-reperfusion injury. Although ischemic preconditioning (PC) is the most powerful form of intrinsic cardioprotection, its application in humans is limited to planned interventions, due to its short duration and technical requirements. However, many organs/tissues are capable of producing "remote" PC (RPC) when subjected to brief bouts of ischemia-reperfusion. RPC was first described in the heart where brief ischemia in one territory led to protection in other area. Later on, RPC started to be used in patients with acute myocardial infarction, albeit with ambiguous results. It is hypothesized that the connection between the signal triggered in remote organ and protection induced in the heart can be mediated by humoral and neural pathways, as well as via systemic response to short sublethal ischemia. However, although RPC has a potentially important clinical role, our understanding of the mechanistic pathways linking the local stimulus to the remote organ remains incomplete. Nevertheless, RPC appears as a cost-effective and easily performed intervention. Elucidation of protective mechanisms activated in the remote organ may have therapeutic and diagnostic implications in the management of myocardial ischemia and lead to development of pharmacological RPC mimetics.

• MeSH
• časové faktory MeSH
• infarkt myokardu metabolismus   patologie   patofyziologie   prevence a kontrola   MeSH
• ischemické přivykání metody   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myokard metabolismus   patologie   MeSH
• regionální krevní průtok MeSH
• reperfuzní poškození myokardu metabolismus   patologie   patofyziologie   prevence a kontrola   MeSH
• signální transdukce MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Increased level of homocysteine (hHcy) in plasma is an accompanying phenomenon of many diseases, including a brain stroke. This study determines whether hyperhomocysteinemia (which is a risk factor of brain ischemia) itself or in combination with ischemic preconditioning affects the ischemia-induced neurodegenerative changes, generation of reactive oxygen species (ROS), lipoperoxidation, protein oxidation, and activity of antioxidant enzymes in the rat brain cortex. The hHcy was induced by subcutaneous administration of homocysteine (0.45 μmol/g body weight) twice a day in 8 h intervals for 14 days. Rats were preconditioned by 5 min ischemia. Two days later, 15 min of global forebrain ischemia was induced by four vessel's occlusion. The study demonstrates that in the cerebral cortex, hHcy alone induces progressive neuronal cell death and morphological changes. Neuronal damage was associated with the pro-oxidative effect of hHcy, which leads to increased ROS formation, peroxidation of lipids and oxidative alterations of cortical proteins. Ischemic reperfusion injury activates degeneration processes and de-regulates redox balance which is aggravated under hHcy conditions and leads to the augmented lipoperoxidation and protein oxidation. If combined with hHcy, ischemic preconditioning could preserve the neuronal tissue from lethal ischemic effect and initiates suppression of lipoperoxidation, protein oxidation, and alterations of redox enzymes with the most significant effect observed after prolonged reperfusion. Increased prevalence of hyperhomocysteinemia in the Western population and crucial role of elevated Hcy level in the pathogenesis of neuronal disorders makes this amino acid as an interesting target for future research. Understanding the multiple etiological mechanisms and recognition of the co-morbid risk factors that lead to the ischemic/reperfusion injury and ischemic tolerance is therefore important for developing therapeutic strategies in human brain stroke associated with the elevated level of Hcy.

• MeSH
• hyperhomocysteinemie komplikace   enzymologie   patologie   MeSH
• krysa rodu rattus MeSH
• oxidace-redukce MeSH
• oxidační stres fyziologie   MeSH
• peroxidace lipidů fyziologie   MeSH
• potkani Wistar MeSH
• přivykání k ischémii trendy   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• reperfuzní poškození enzymologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• kardioprotektivní intervence, mitochondrial permeability transition pore,
• MeSH
• biologická adaptace MeSH
• hypoxie MeSH
• iontový transport MeSH
• ischemická choroba srdeční * patologie   MeSH
• ischemický postconditioning MeSH
• ischemie MeSH
• KATP kanály fyziologie   MeSH
• lidé MeSH
• membránový potenciál mitochondrií MeSH
• mitogenem aktivované proteinkinasy MeSH
• odolnost vůči nemocem fyziologie   MeSH
• oxid dusnatý MeSH
• přivykání k ischémii MeSH
• reaktivní formy kyslíku škodlivé účinky   MeSH
• reperfuze myokardu MeSH
• signální transdukce MeSH
• srdeční mitochondrie * enzymologie   fyziologie   účinky léků   ultrastruktura   MeSH
• vápník fyziologie   MeSH
• zdraví kojenců MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH