Extracellular potassium concentration might modify electrophysiological properties in the border zone of ischemic myocardium. We evaluated the depolarization and repolarization characteristics across the ischemic-normal border under [K+] variation. Sixty-four-lead epicardial mapping was performed in 26 rats ([K+] 2.3-6.4 mM) in a model of acute ischemia/reperfusion. The animals with [K+] < 4.7 mM (low-normal potassium) had an ischemic zone with ST-segment elevation and activation delay, a border zone with ST-segment elevation and no activation delay, and a normal zone without electrophysiological abnormalities. The animals with [K+] >4.7 mM (normal-high potassium) had only the ischemic and normal zones and no transitional area. Activation-repolarization intervals and local conduction velocities were inversely associated with [K+] in linear regression analysis with adjustment for the zone of myocardium. The reperfusion extrasystolic burden (ESB) was greater in the low-normal as compared to normal-high potassium animals. Ventricular tachycardia/fibrillation incidence did not differ between the groups. In patch-clamp experiments, hypoxia shortened action potential duration at 5.4 mM but not at 1.3 mM of [K+]. IK(ATP) current was lower at 1.3 mM than at 5.4 mM of [K+]. We conclude that the border zone formation in low-normal [K+] was associated with attenuation of IK(ATP) response to hypoxia and increased reperfusion ESB.

• MeSH
• akční potenciály * fyziologie   MeSH
• draslík * krev   metabolismus   MeSH
• ischemická choroba srdeční * patofyziologie   krev   metabolismus   MeSH
• krysa rodu rattus MeSH
• potkani Wistar MeSH
• reperfuzní poškození myokardu krev   patofyziologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Experimental and clinical studies have clearly demonstrated significant sex differences in myocardial structure and function, both under physiological and pathological conditions. The best example are significant sex differences in the cardiac tolerance to ischemia/reperfusion injury: pre-menopausal adult female hearts are more resistant as compared to the male myocardium. The importance of these findings is supported by the fact that the number of studies dealing with this issue increased significantly in recent years. Detailed molecular and cellular mechanisms responsible for sex differences are yet to be elucidated; however, it has been stressed that the differences cannot be explained only by the effect of estrogens. In recent years, a promising new hypothesis has been developed, suggesting that mitochondria may play a significant role in the sex differences in cardiac tolerance to oxygen deprivation. However, one is clear already today: sex differences are so important that they should be taken into consideration in the clinical practice for the selection of the optimal diagnostic and therapeutic strategy in the treatment of ischemic heart disease. The present review attempts to summarize the progress in cardiovascular research on sex-related differences in cardiac tolerance to oxygen deprivation during the last 40 years, i.e. from the first experimental observation. Particular attention was paid to the sex-related differences of the normal heart, sex-dependent tolerance to ischemia-reperfusion injury, the role of hormones and, finally, to the possible role of cardiac mitochondria in the mechanism of sex-dependent differences in cardiac tolerance to ischemia/reperfusion injury. Key words: Female heart, Cardiac hypoxic tolerance, Ischemia-reperfusion injury, Sex differences.

• MeSH
• kyslík metabolismus   MeSH
• lidé MeSH
• myokard metabolismus   patologie   MeSH
• pohlavní dimorfismus * MeSH
• reperfuzní poškození myokardu metabolismus   patofyziologie   MeSH
• sexuální faktory MeSH
• srdeční mitochondrie metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Increased level of C-reactive protein (CRP) is a risk factor for cardiovascular diseases, including myocardial infarction and hypertension. Here, we analyzed the effects of CRP overexpression on cardiac susceptibility to ischemia/reperfusion (I/R) injury in adult spontaneously hypertensive rats (SHR) expressing human CRP transgene (SHR-CRP). Using an in vivo model of coronary artery occlusion, we found that transgenic expression of CRP predisposed SHR-CRP to repeated and prolonged ventricular tachyarrhythmias. Excessive ischemic arrhythmias in SHR-CRP led to a significant reduction in infarct size (IS) compared with SHR. The proarrhythmic phenotype in SHR-CRP was associated with altered heart and plasma eicosanoids, myocardial composition of fatty acids (FAs) in phospholipids, and autonomic nervous system imbalance before ischemia. To explain unexpected IS-limiting effect in SHR-CRP, we performed metabolomic analysis of plasma before and after ischemia. We also determined cardiac ischemic tolerance in hearts subjected to remote ischemic perconditioning (RIPer) and in hearts ex vivo. Acute ischemia in SHR-CRP markedly increased plasma levels of multiple potent cardioprotective molecules that could reduce IS at reperfusion. RIPer provided IS-limiting effect in SHR that was comparable with myocardial infarction observed in naïve SHR-CRP. In hearts ex vivo, IS did not differ between the strains, suggesting that extra-cardiac factors play a crucial role in protection. Our study shows that transgenic expression of human CRP predisposes SHR-CRP to excess ischemic ventricular tachyarrhythmias associated with a drop of pump function that triggers myocardial salvage against lethal I/R injury likely mediated by protective substances released to blood from hypoxic organs and tissue at reperfusion.

• MeSH
• akční potenciály MeSH
• C-reaktivní protein genetika   metabolismus   MeSH
• fibrilace komor etiologie   metabolismus   patofyziologie   MeSH
• hypertenze komplikace   metabolismus   patofyziologie   MeSH
• komorová tachykardie etiologie   metabolismus   patofyziologie   MeSH
• krevní tlak MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myokard metabolismus   patologie   MeSH
• potkani inbrední SHR MeSH
• potkani transgenní MeSH
• reperfuzní poškození myokardu etiologie   metabolismus   patofyziologie   prevence a kontrola   MeSH
• srdeční frekvence MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Epidemiological studies have demonstrated a relationship between the adverse influence of perinatal development and increased risk of ischemic heart disease in adults. From negative factors to which the fetus is subjected, the most important is hypoxia. The fetus may experience hypoxic stress under different conditions, including pregnancy at high altitude, pregnancy with anemia, placental insufficiency, and heart, lung, and kidney disease. One of the most common insults during the early stages of postnatal development is hypoxemia due to congenital cyanotic heart defects. Experimental studies have demonstrated a link between early hypoxia and increased risk of ischemia/reperfusion injury (I/R) in adults. Furthermore, it has been observed that late myocardial effects of chronic hypoxia, experienced in early life, may be sex-dependent. Unlike in males, perinatal hypoxia significantly increased cardiac tolerance to acute I/R injury in adult females, expressed as decreased infarct size and lower incidence of ischemic arrhythmias. It was suggested that early hypoxia may result in sex-dependent programming of specific genes in the offspring with the consequence of increased cardiac susceptibility to I/R injury in adult males. These results would have important clinical implications, since cardiac sensitivity to oxygen deprivation in adult patients may be significantly influenced by perinatal hypoxia in a sex-dependent manner.

• MeSH
• dospělí MeSH
• hypoxie plodu komplikace   patofyziologie   MeSH
• ischemická choroba srdeční epidemiologie   etiologie   patofyziologie   MeSH
• kyslík metabolismus   MeSH
• lidé MeSH
• reperfuzní poškození myokardu epidemiologie   etiologie   patofyziologie   MeSH
• rizikové faktory MeSH
• sexuální faktory MeSH
• srdce embryologie   patofyziologie   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice epidemiologie   etiologie   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The mechanism of reentrant ventricular tachyarrhythmias complicating acute myocardial ischemia is largely based on the interaction between an arrhythmogenic substrate and triggers. Melatonin was proposed as an antiarrhythmic medication and was shown to ameliorate the arrhythmogenic substrate. Also, melatonin provides a sympatholytic effect in different settings and might attenuate ectopic activity, which provides reentry triggers. In the present study, we aimed at evaluating the melatonin effects on cardiac sympathetic activity and the incidence of premature ventricular beats during the episode of ischemia-reperfusion. Experiments were done in a total of 26 control and 28 melatonin-treated (10 mg/kg, daily, for 7 days) male rats. Sympathetic fibers density was assessed by glyoxylic acid-induced fluorescence. Continuous electrocardiograms recording was performed during ischemia-reperfusion episodes (5 min/5 min, respectively) induced by reversible coronary occlusion. Myocardial expression of tyrosine hydroxylase, a rate-limiting enzyme of catecholamine biosynthesis was assessed by Western blotting. No differences in the state of sympathetic innervation were observed in histochemical analysis. However, Western blotting analysis demonstrated that melatonin treatment suppressed tyrosine hydroxylase expression in the non-ischemic (p < 0.05 versus control) but not ischemic regions of myocardium. The melatonin-treated animals had longer RR-intervals in the baseline state than the control animals (264 ± 48 ms versus 237 ± 33 ms, p = 0.044, respectively), but this difference decayed during the period of ischemia due to the increase of heart rate in the treated group. The number of premature ventricular beats did not differ between the control and treated groups during the ischemic and reperfusion periods. One-week melatonin pretreatment caused a slight peripheral sympatholytic effect that attenuated during ischemia and completely disappeared by the onset of reperfusion. The slight expression of sympathetic downregulation was associated with the lack of any effect of melatonin on extrasystolic burden. Collectively, the data suggest that melatonin cannot target the triggers of reentrant arrhythmias.

• MeSH
• antiarytmika aplikace a dávkování   farmakologie   MeSH
• elektrokardiografie MeSH
• ischemická choroba srdeční farmakoterapie   patofyziologie   MeSH
• komorová tachykardie etiologie   prevence a kontrola   MeSH
• krysa rodu rattus MeSH
• melatonin aplikace a dávkování   farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• potkani Wistar MeSH
• reperfuzní poškození myokardu farmakoterapie   patofyziologie   MeSH
• srdeční frekvence účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The effect of preventive administration of melatonin on the arrhythmogenic substrate in the myocardium was studied in the rabbit model of acute ischemia/reperfusion in vivo. The animals treated with melatonin 60 min before ischemia induction had shorter median activation time compared to the control group (p=0.039), less pronounced shortening of repolarization durations in the ischemic zone during coronary occlusion (p=0.008), and more complete recovery of repolarization during reperfusion (p=0.027). In the melatonin group, the dispersion of repolarization was less than in the control group during both ischemic period (p=0.043) and reperfusion (p=0.038). Thus, preventive administration of melatonin mitigated the arrhythmogenic substrate in the heart under conditions of ischemia/reperfusion.

• MeSH
• ischemická choroba srdeční farmakoterapie   patofyziologie   MeSH
• králíci MeSH
• melatonin terapeutické užití   MeSH
• reperfuzní poškození myokardu farmakoterapie   patofyziologie   MeSH
• srdce fyziologie   MeSH
• srdeční elektrofyziologie MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Chronic continuous normobaric hypoxia (CNH) increases cardiac tolerance to ischemia/reperfusion injury in vivo and this effect is mediated via µ and delta2 opioid receptors (ORs) activation. CNH has also been shown to be cardioprotective in isolated rat heart. In this study, we hypothesize that this cardioprotective effect of CNH is mediated by activation of µ and delta2 ORs and preservation of mitochondrial function. Hearts from rats adapted to CNH (12 % oxygen) for 3 weeks were extracted, perfused in the Langendorff mode and subjected to 45 min of global ischemia and 30 min of reperfusion. Intervention groups were pretreated for 10 min with antagonists for different OR types: naloxone (300 nmol/l), the selective delta OR antagonist TIPP(psi) (30 nmol/l), the selective delta1 OR antagonist BNTX (1 nmol/l), the selective delta2 OR antagonist naltriben (1 nmol/l), the selective peptide µ OR antagonist CTAP (100 nmol/l) and the selective delta OR antagonist nor-binaltorphimine (3 nmol/l). Creatine kinase activity in coronary effluent and cardiac contractile function were monitored to assess cardiac injury and functional impairment. Additionally, cardiac tissue was collected to measure ATP and to isolate mitochondria to measure respiration rate and calcium retention capacity. Adaptation to CNH decreased myocardial creatine kinase release during reperfusion and improved the postischemic recovery of contractile function. Additionally, CNH improved mitochondrial state 3 and uncoupled respiration rates, ADP/O, mitochondrial transmembrane potential and calcium retention capacity and myocardial ATP level during reperfusion compared to the normoxic group. These protective effects were completely abolished by naloxone, TIPP(psi), naltriben, CTAP but not BNTX or nor-binaltorphimine. These results suggest that cardioprotection associated with adaptation to CNH is mediated by µ and delta2 opioid receptors activation and preservation of mitochondrial function.

• MeSH
• hypoxie patofyziologie   MeSH
• krysa rodu rattus MeSH
• narkotika - antagonisté farmakologie   MeSH
• orgánové kultury - kultivační techniky MeSH
• potkani Wistar MeSH
• receptory opiátové delta antagonisté a inhibitory   fyziologie   MeSH
• receptory opiátové mu antagonisté a inhibitory   fyziologie   MeSH
• reperfuzní poškození myokardu patofyziologie   prevence a kontrola   MeSH
• srdeční mitochondrie účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Electrocardiographic Tpeak -Tend interval (Tp-Te) is a promising marker for the prediction of ventricular tachycardia and/or ventricular fibrillation (VT/VF). The study was aimed to compare single-lead vs multilead Tp-Te variables as VT/VF predictors in experimental ischemia/reperfusion model. METHODS AND RESULTS: Computer simulations were done using the ECGSIM model with an ischemic region set in anterior left ventricular apex. In 18 anesthetized cats, myocardial ischemia was induced by 30-minute ligation of left anterior descending coronary artery followed by reperfusion. Body surface ECGs in limb leads and modified precordial leads were recorded. Tp-Te was detected automatically in individual leads with a custom-designed parametric algorithm. Tp-Te dispersion and total Tp-Te were calculated as a difference between the maximal and minimal value of individual Tp-Te(s) and an interval between the earliest Tpeak and the latest Tend throughout all leads, respectively. Simulations showed that the increase of local, but not total, dispersion of repolarization characteristic for ischemic damage led to nonuniform shortening of T-peak times across 12 standard leads, which in turn resulted in the increase of single-lead Tp-Te(s), total Tp-Te and Tp-Te dispersion. Animals experienced VT/VF showed increased Tp-Te dispersion and total Tp-Te during reperfusion. In univariate logistic regression analysis, only the Tp-Te dispersion at the beginning of reperfusion was associated with the VT/VF incidence. According to ROC curve analysis, the optimal cut-off value of the Tp-Te dispersion was 17 ms (sensitivity 0.71, specificity 0.80). CONCLUSIONS: The reperfusion VT/VFs were independently predicted by increased Tp-Te dispersion, which suggests the importance of multi-lead evaluation of Tp-Te intervals.

• MeSH
• akční potenciály * MeSH
• časové faktory MeSH
• elektrokardiografie * MeSH
• fibrilace komor diagnóza   etiologie   patofyziologie   MeSH
• kočky MeSH
• komorová tachykardie diagnóza   etiologie   patofyziologie   MeSH
• modely kardiovaskulární MeSH
• modely nemocí na zvířatech MeSH
• počítačová simulace MeSH
• prediktivní hodnota testů MeSH
• reperfuzní poškození myokardu diagnóza   etiologie   patofyziologie   MeSH
• rizikové faktory MeSH
• srdeční frekvence * MeSH
• zvířata MeSH
• Check Tag
• kočky MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie 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

Age and sex play an essential role in the cardiac tolerance to ischemia-reperfusion injury: cardiac resistance significantly decreases during postnatal maturation and the female heart is more tolerant than the male myocardium. It is widely accepted that mitochondrial dysfunction, and particularly mitochondrial permeability transition pore (MPTP) opening, plays a major role in determining the extent of cardiac ischemia-reperfusion injury. We have observed that the MPTP sensitivity to the calcium load differs in mitochondria isolated from neonatal and adult myocardium, as well as from adult male and female hearts. Neonatal and female mitochondria are more resistant both in the extent and in the rate of mitochondrial swelling induced by high calcium concentration. Our data further suggest that age- and sex-dependent specificity of the MPTP is not the result of different amounts of ATP synthase and cyclophilin D: neonatal and adult hearts, similarly as the male and female hearts, contain comparable amounts of MPTP and its regulatory protein cyclophilin D. We can speculate that the lower sensitivity of MPTP to the calcium-induced swelling may be related to the higher ischemic tolerance of both neonatal and female myocardium.

• MeSH
• lidé MeSH
• pohlavní dimorfismus * MeSH
• reperfuzní poškození myokardu metabolismus   patologie   patofyziologie   MeSH
• srdce * patofyziologie   MeSH
• srdeční mitochondrie metabolismus   patologie   MeSH
• transportní proteiny mitochondriální membrány metabolismus   MeSH
• vápník metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH