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
Introduction: Na experimentálnu verifikáciu vitality žalúdočného tubulu pred ezofagektómiou je nevyhnutná existencia jednoduchého modelu. Ischémia je hlavná príčina dehiscencie ezofagogastrickej anastomózy a následného leaku anastomózy. Ischemická príprava žalúdočného tubulu pred ezofagektómiou je potencionálna možnosť ako zamedziť rozvoju nežiaducich komplikácií. Avšak technika ako aj optimálne načasovanie ischemizácie ostávajú nejasné. Metody: Samce potkanov plemena Sprague-Dawley (n=24) boli náhodne rozdelené do štyroch skupín: ischemická skupina s odberom vzoriek po 1 hodine od ischémie (I1H), ischemická skupina s odberom vzoriek 1 deň od ischémie (I1D), ischemická skupina s odberom vzoriek 7 dní od ischémie (I7D) a kontrolná skupina (C). Ischémia bola navodená ligáciou a. gastrica sinistra a aa. gastricae breves. Vzorky boli histologicky a makroskopicky verifikované a stanovený bol počet a percentuálne zastúpenie jednotlivých imunokompetentných buniek. Výsledky: V skupine I1H bola pozorovaná ischemická denudácia s mukozálnymi eróziami a celkový počet eozinofilov bol signifikantne vyšší (p<0.05) v tejto skupine v porovnaní so skupinami I1D a I7D. V skupine I1D bola pozorovaná redukcia zápalu a parciálna regenerácia žalúdočnej mukózy. V skupine I7D bola pozorovaná takmer kompletná architektonická regenerácia žalúdočného epitelu a počet polymorfonukleárov bol signifikantne nižší (p<0,05) ako v skupine I1D. Záver: Ischemické poškodenie ligáciou žalúdočných tepien bolo predominantne pozorované v skupinách I1H a I1D avšak nie v skupine I7D. Táto práca prezentuje jednoduchú metódu verifikácie ischemických zmien žalúdočného tubulu.
Introduction: A reproducible and simple model is essential for verifying gastric conduit vitality before esophagectomy. Ischemia is a major cause of esophagogastric anastomotic dehiscence and leakage. Ischemic conditioning of the stomach prior to esophageal surgery has been shown to lower the incidence of postoperative complications, including anastomotic leakage. However, the optimal timing and technique of ischemization remain uncertain. Methods: Male Sprague-Dawley rats (n=24) were randomly divided into four groups: ischemic group – samples collected 1 hour after ischemia (I1H), ischemic group – samples collected 1 day after ischemia (I1D), ischemic group – samples collected 7 days after ischemia (I7D), and control group (C). Ischemia was induced by ligation of the left gastric (LGA) and short gastric arteries (SGA). The samples were verified using histological and macroscopic analysis, and the number and percentage of immunocompetent cells were determined. Results: One hour after ischemization (I1H), ischemic denudation with mucosal erosion was observed, and the total number of eosinophils was significantly higher (p<0.05) in the I1H group compared to the I1D and I7D groups. One day after ischemia (I1D), there was a reduction in the inflammatory response with partial regeneration of gastric mucosa. In the I7D group, nearly complete architectural regeneration of mucosal epithelium was documented. The total count of polymorphonuclears was significantly lower (p<0.05) compared to the I1D group. Conclusion: Ischemic mucosal injury after LGA and SGA ligation was observed dominantly in the I1H and I1D groups, but not in I7D group. In conclusion, this study presents a simple method for verifying gastric ischemic changes.
- MeSH
- anastomóza chirurgická * MeSH
- ezofagektomie metody MeSH
- ezofágus chirurgie krevní zásobení patologie MeSH
- ischemický postconditioning metody MeSH
- krysa rodu rattus MeSH
- netěsnost anastomózy etiologie prevence a kontrola MeSH
- potkani Sprague-Dawley MeSH
- žaludek chirurgie krevní zásobení patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata 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
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
- 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
The protective effects of ischemic postconditioning (IPC) and nitric oxide (NO) administration have been demonstrated in several ischemic scenarios. However, current evidence regarding the effect of IPC and NO in extracorporeal cardiopulmonary resuscitation remains lacking. Fifteen female swine (body weight 45 kg) underwent veno-arterial extracorporeal membrane oxygenation (ECMO) implantation; cardiac arrest-ventricular fibrillation was induced by rapid ventricular pacing. After 20 min of cardiac arrest, blood flow was restored by increasing the ECMO flow rate to 4.5 L/min. The animals (five per group) were then randomly assigned to receive IPC (three cycles of 3 min ischemia and reperfusion), NO (80 ppm via oxygenator), or mild hypothermia (HT; 33.0°C). Cerebral oximetry and aortic blood pressure were monitored continuously. After 90 min of reperfusion, blood samples were drawn for the measurement of troponin I, myoglobin, creatine-phosphokinase, alanine aminotransferase, neuron-specific enolase, cystatin C, and reactive oxygen metabolite (ROM) levels. Significantly higher blood pressure and cerebral oxygen saturation values were observed in the HT group compared with the IPC and NO groups (P < 0.05). The levels of troponin I, myoglobin, creatine phosphokinase, and alanine aminotransferase were significantly lower in the HT group (P < 0.05); levels of neuron-specific enolase, cystatin C, and ROM were not significantly different. IPC and NO were comparable in all monitored parameters. The results of the present study indicate that IPC and NO administration are not superior interventions to HT for the maintenance of blood pressure, cerebral oxygenation, organ protection, and suppression of oxidative stress following extracorporeal cardiopulmonary resuscitation.
- MeSH
- alanintransaminasa krev MeSH
- cystatin C krev MeSH
- fosfopyruváthydratasa krev MeSH
- ischemický postconditioning metody MeSH
- kardiopulmonální resuscitace metody MeSH
- kreatinkinasa krev MeSH
- krevní tlak MeSH
- mimotělní membránová oxygenace metody MeSH
- modely nemocí na zvířatech MeSH
- myoglobin krev MeSH
- ochranné látky terapeutické užití MeSH
- oxid dusnatý terapeutické užití MeSH
- oxidační stres MeSH
- prasata MeSH
- reaktivní formy kyslíku krev MeSH
- troponin I krev MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Although there are abundant data on ischemic postconditioning (IPoC) in the adult myocardium, this phenomenon has not yet been investigated in neonatal hearts. To examine possible protective effects of IPoC, 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 by an isometric force transducer. Hearts were exposed to 40 or 60 min of global ischemia followed by reperfusion up to the maximum recovery of DF. IPoC was induced by three cycles of 10, 30 or 60 s periods of global ischemia/reperfusion. To further determine the extent of ischemic injury, lactate dehydrogenase (LDH) release was measured in the coronary effluent. Tolerance to ischemia did not change from day 1 to day 4 but decreased to days 7 and 10. None of the postconditioning protocols tested led to significant protection on the day 10. Prolonging the period of sustained ischemia to 60 min on day 10 did not lead to better protection. The 3x30 s protocol was then evaluated on days 1, 4 and 7 without any significant effects. There were no significant differences in LDH release between postconditioned and control groups. It can be concluded that neonatal hearts cannot be protected by ischemic postconditioning during first 10 days of postnatal life.
- MeSH
- ischemická choroba srdeční patofyziologie MeSH
- ischemický postconditioning * MeSH
- L-laktátdehydrogenasa sekrece MeSH
- novorozená zvířata MeSH
- potkani Wistar MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
Cardiac surgery patients are now more risky in terms of age, comorbidities, and the need for complex procedures. It brings about reperfusion injury, which leads to dysfunction and/or loss of part of the myocardium. These groups of patients have a higher incidence of postoperative complications and mortality. One way of augmenting intraoperative myocardial protection is the phenomenon of myocardial conditioning, elicited with brief nonlethal episodes of ischaemia-reperfusion. In addition, drugs are being tested that mimic ischaemic conditioning. Such cardioprotective techniques are mainly focused on reperfusion injury, a complex response of the organism to the restoration of coronary blood flow in ischaemic tissue, which can lead to cell death. Extensive research over the last three decades has revealed the basic mechanisms of reperfusion injury and myocardial conditioning, suggesting its therapeutic potential. But despite the enormous efforts that have been expended in preclinical studies, almost all cardioprotective therapies have failed in the third phase of clinical trials. One reason is that evolutionary young cellular mechanisms of protection against oxygen handling are not very robust. Ischaemic conditioning, which is among these, is also limited by this. At present, the prevailing belief is that such options of treatment exist, but their full employment will not occur until subquestions and methodological issues with the transfer into clinical practice have been resolved.
- MeSH
- adjuvancia farmaceutická terapeutické užití MeSH
- ischemický postconditioning MeSH
- kardiochirurgické výkony * škodlivé účinky MeSH
- kardiotonika terapeutické užití MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Postconditioning (PostC) is a recently discovered phenomenon whereby brief repetitive cycles of ischaemia with intermittent reperfusion following prolonged ischaemia elicit cardioprotection. This study investigated whether the age, genetic characteristics or number of repetitive cycles influenced the protective effect of PostC in mice. C57BL/6 floxed or non-floxed STAT-3 mice aged between 14-16 weeks (young) or 18-20 weeks (older) were perfused on a Langendorff apparatus and subjected to 35 min global ischaemia and 45 min reperfusion. PostC was elicited by either 3 (PostC-3) or 6 cycles (PostC-6) of 10s ischaemia and 10 s reperfusion. PostC-3 and PostC-6 in both young and older non-floxed mice reduced the myocardial infarct size. In contrast, only PostC-3 reduced myocardial infarct size in young floxed mice. Neither PostC-3 nor PostC-6 reduced the infarct in older floxed mice. Our data reveal that genetic characteristics, a minute difference in age or the number of postconditioning cycles are critical factors to be considered for the successful effect of ischaemic postconditioning in a murine model. Moreover, these factors should be taken into consideration for future experimental research or clinical applications of this protective phenomenon.
- MeSH
- infarkt myokardu genetika patologie prevence a kontrola MeSH
- ischemická choroba srdeční genetika patologie prevence a kontrola MeSH
- ischemický postconditioning MeSH
- myokard patologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- transkripční faktor STAT3 metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
Chirurgické výkony jsou nedílně spojeny s aplikací inhalačních a intravenózních anestetik. Kardioprotektivní účinky anestetik jsou jednak přímé, pozitivním ovlivněním poměru mezi dodávkou a spotřebou kyslíku v myokardu, jednak nepřímé, ovlivněním funkce kardiomyocytů na úrovni buněčných membrán, iontových kanálů a regulačních enzymů. Anestetika rovněž vstupují do interakcí s mechanismy ischemického preconditioningu a postconditioningu. Klinické studie potvrdily, že anestetika použitá během operace mají vliv i na pooperační průběh. Detailnější znalost kardioprotektivních mechanismů a účinků anestetik, spolu s objasněním účinnosti jednotlivých anesteziologických protokolů, by měla umožnit cílené využití anestetik v klinické praxi s poklesem kardiovaskulárních komplikací po chirurgických výkonech.
Surgical procedures are invariably accompanied by the use of inhalational and intravenous anesthetics. Anesthetics have direct cardioprotective eff ects by positive infl uence on the myocardial oxygen supply/demand ratio, and indirect by the infl uence on cardiomyocyte function at the level of cell membranes, ion channels and regulatory enzymes. Anesthetics also interact with subcellular mechanisms of ischemic preconditioning and postconditioning. The results of clinical studies confi rmed the fact that anesthetics infl uence also postoperative course. Detailed knowledge of cardioprotective eff ects of anesthetics, together with clarifi cation of eff ectiveness of particular anesthesia protocols, should lead to targeted use of anesthetics resulting in decreased frequency of cardiovascular complications after surgical procedures.
- Klíčová slova
- ischemicko-reperfuzní poškození myokardu, inhalační anestetika, intravenózní anestetika, preconditioning, postconditioning,
- MeSH
- anestetika inhalační aplikace a dávkování farmakologie MeSH
- anestetika intravenózní aplikace a dávkování farmakologie MeSH
- financování organizované MeSH
- ischemický postconditioning MeSH
- kardiochirurgické výkony metody MeSH
- kardiomyocyty účinky léků MeSH
- kardiovaskulární systém účinky léků MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- modely u zvířat MeSH
- pooperační komplikace mortalita MeSH
- pooperační období MeSH
- přivykání k ischémii MeSH
- syndrom omráčeného myokardu farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
