We compared the effects of adaptation to intermittent high altitude (IHA) hypoxia of various degree and duration on ischemia-induced ventricular arrhythmias in rats. The animals were exposed to either relatively moderate hypoxia of 5000 m (4 or 8 h/day, 2-3 or 5-6 weeks) or severe hypoxia of 7000 m (8 h/day, 5-6 weeks). Ventricular arrhythmias induced by coronary artery occlusion were assessed in isolated buffer-perfused hearts or open-chest animals. In the isolated hearts, both antiarrhythmic and proarrhythmic effects were demonstrated depending on the degree and duration of hypoxic exposure. Whereas the adaptation to 5000 m for 4 h/day decreased the total number of premature ventricular complexes (PVCs), extending the daily exposure to 8 h and/or increasing the altitude to 7000 m led to opposite effects. On the contrary, the open-chest rats adapted to IHA hypoxia exhibited an increased tolerance to arrhythmias that was even more pronounced at the higher altitude. The distribution of PVCs over the ischemic period was not altered by any protocol of adaptation. It may be concluded that adaptation to IHA hypoxia is associated with enhanced tolerance of the rat heart to ischemic arrhythmias unless its severity exceeds a certain upper limit. The opposite effects of moderate and severe hypoxia on the isolated hearts cannot be explained by differences in the occluded zone size, heart rate or degree of myocardial fibrosis. The proarrhythmic effect of severe hypoxia may be related to a moderate left ventricular hypertrophy (27 %), which was present in rats adapted to 7000 m but not in those adapted to 5000 m. This adverse effect can be overcome by an unknown protective mechanism(s) that is absent in the isolated hearts., G. Asemu, J. Neckář, O. Szárszoi, F. Papoušek, B. Ošťádal, F. Kolář., and Obsahuje bibliografii
An important mechanism underlying cochlear hair cell (HC) susceptibility to hypoxia/ischemia is the influx of Ca2+. Two main ATP-dependent mechanisms contribute to maintaining low Ca2+ levels: uptake of Ca2+ into intracellular stores via smooth endoplasmic reticulum calcium ATPase (SERCA) and extrusion of Ca2+ via plasma membrane calcium ATPase (PMCA). The effects of the SERCA inhibitors thapsigargin (10 nM-10 μM) and cyclopiazonic acid (CPA; 10-50 μM) and of the PMCA blockers eosin (1.5-10 μM) and o-vanadate (1-5 mM) on inner and outer hair cells (IHCs/OHCs) were examined in normoxia and ischemia using an in vitro model of the newborn rat cochlea. Exposure of the cultures to ischemia resulted in a significant loss of HCs. Thapsigargin and CPA had no effect. Eosin decreased the numbers of IHCs and OHCs by up to 25 % in normoxia and significantly aggravated the ischemia-induced damage to IHCs at 5 and 10 μM and to OHCs at 10 μM. o-Vanadate had no effect on IHC and OHC counts in normoxia, but aggravated the ischemia-induced HC loss in a dose-dependent manner. The effects of eosin and o-vanadate indicate that PMCA has an important role to play in protecting the HCs from ischemic cell death., N. Amarjargal, B. Mazurek, H. Haupt, N. Andeeva, J. Fuchs, J. Gross., and Obsahuje bibliografii a bibliografické odkazy
Estrogen replacement therapy could play a role in the reduction of injury associated with cerebral ischemia in vivo, which could be, at least partially, a consequence of estrogen influence of glutamate buffering by astrocytes during hypoxia/ischemia. Estrogen exerts biological effects through interaction with its two receptors: estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), which are both expressed in astrocytes. This study explored effects of hypoxia and glucose deprivation (HGD), alone or followed by 1 h recovery, on ERα and ERβ expression in primary rat astrocyte cultures following 1 h exposure to: a) 5 % CO2 in air (control group-CG); b) 2 % O2/5 % CO2 in N2 with glucose deprivation (HGD group-HGDG); or c) the HGDG protocol followed by 1 h CG protocol (recovery group-RG). ER α mRNA expression decreased in HGDG. At the protein level, full-length ER α (67 kDa) and three ER α -immunoreactive protein bands (63, 60 and 52 kDa) were detected. A significant decrease in the 52 kDa band was seen in HGDG, wh ile a significant decrease in expression of the full length ERα was seen in the RG. ERβ mRNA and protein expression (a 54 kDa single band) did not change. The observed decrease in ER α protein may limit estrogen-mediated signalling in astrocytes during hypoxia and recovery., M. D. Al-Bader, S. A. Malatiali, Z. B. Redzic., and Obsahuje bibliografii a bibliografické odkazy
Photothrombotic model of ischemia (PT) is based on free radical-mediated endothelial dysfunction followed by thrombosis. Free radicals are also involved in hypoxic preconditioning. We tested the sensitivity of PT to preconditioning with hypobaric hypoxia and to pretreatment with melatonin. In adult Wistar rats, after intravenous application of Rose Bengal, a stereo-tactically defined spot on the denuded skull was irradiated by a laser for 9 min. The first experimental group underwent hypobaric hypoxia three days before irradiation. In the second experimental group, melatonin was applied intraperitoneally one hour before irradiation. Three days after irradiation, animals were sacrificed, the brains perfused, and stained with TTC. Ischemic lesions were divided into grades (I, II, III). In the control group (where no manipulation preceded photothrombosis), most animals displayed deep damage involving the striatum (grade III). The group pre-exposed to hypoxia showed similar results. Only 28.57 % of the melatonin pretreated animals exhibited grade III lesions, and in 57.14 % no signs of lesions were detected. Pre-exposure to hypoxia was not protective in our model. Pretreatment with melatonin lead to a significant reduction of the number of large ischemic lesions. This result is probably caused by protection of endothelial cells by melatonin., I. Matějovská, K. Bernášková, D. Krýsl, J. Mareš., and Obsahuje bibliografii a bibliografické odkazy
The goal of the study was to determine whether postconditioning protects against different ischemia durations in the rabbit. Rabbits were assigned to a 20-, 25-, 45- or 60-min coronary occlusion followed by 24-h of reperfusion. Rabbits received no further intervention (control) or were postconditioned with four cycles of 30-s occlusion and 30-s reperfusion after myocardial infarction. Plasma levels of troponin I were quantified throughout reperfusion. In control conditions, infarct sizes (% area at risk using triphenyltetrazolium chloride) after 20, 25, 45 and 60 min of coronary occlusions were 23±3, 51±4, 70±3 and 81±3 %, respectively. With 20 and 25 min occlusion, postconditioning reduced infarct size by 43±10 and 73±21 %, respectively. On the other hand, with 45 or 60 min occlusion, postconditioning had no significant effects on infarct size (61±3 and 80±2 % of area at risk). Preconditioning protocol was performed with 25- and 60-min coronary occlusion. As expected, preconditioning significantly reduced infarct size. In conclusion, in the rabbit, the cardioprotection afforded by postconditioning is limited to less than 45 min coronary occlusion., R. Létienne, Y. Calmettes, B. Le Grand., and Obsahuje seznam literatury
Dysfunction of mitochondria induced by ischemia is considered to be a key event triggering neuronal cell death after brain ischemia. Here we report the effect of ischemia-reperfusion on mitochondrial protein synthesis and activity of cytochrome c oxidase (EC 1.9.3.1, COX). By performing 4-vessel occlusion model of global brain ischemia, we have observed that 15 min of global ischemia led to the inhibition of COX subunit I (COXI) synthesis to 56 % of control. After 1, 3 and 24 h of reperfusion, COXI synthesis was inhibited to 46, 50 and 72 % of control, respectively. Depressed synthesis of COXI was not a result of either diminished transcription of COXI gene or increased proteolytic degradation of COXI, since both Northern hybridization and Western blotting did not show significant changes in COXI mRNA and protein level. Thus, ischemia-reperfusion affects directly mitochondrial translation machinery. In addition, ischemia in duration of 15 min and consequent 1, 3 and 24 h of reperfusion led to the inhibition of COX activity to 90.3, 80.3, 81.9 and 83.5 % of control, respectively. Based on our data, we suggest that inhibition of COX activity is rather caused by ischemia-induced modification of COX polypeptides than by inhibition of mitochondrial translation., P. Racay ... [et al.]., and Obsahuje seznam literatury
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., Jozef Burda, Rastislav Burda., and Obsahuje bibliografii
Perinatal hypoxemia may have serious long-term effects on the adult cardiovascular system and may lead to sex-dependent changes in cardiac tolerance to acute ischemia in adult life. The aim of the study was to answer the question whether gonadectomy of the male and female rats in the early phase of ontogenetic development affects the late effect of perinatal hypoxia. Pregnant Wistar rats were placed into a normobaric hypoxic chamber (12 % O2) 7 days before the expected date of delivery. Newborn pups were kept in the chamber with their mothers for another 5 days after birth. After hypoxic exposure all animals were kept for 3 months in room air. Some of the pups were gonadectomized right after removal from the hypoxic chamber. Ventricular arrhythmias were assessed on isolated perfused hearts. Castration did not influence arrhythmogenesis in the adult normoxic or perinatally hypoxic female hearts. Nevertheless, the number of arrhythmias was decreased in perinatally hypoxic gonadectomized males. In conclusion, we have shown that perinatal normobaric hypoxia increased cardiac tolerance to acute ischemia in adult male rats; however, it had no late effect in females. Gonadectomy did not affect arrhythmogenesis in both normoxic and hypoxic female hearts, whereas in males significantly decreased the number of arrhythmias., I. Netuka ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Chronic intermittent hypoxia (CIH ) is associated with increased production of reactive oxygen species that contributes to the adaptive mechanism underlying the improved myocardial ischemic tolerance. The aim was to find out whether the antioxidative enzyme manganese superoxide dismutase (MnSOD) can play a role in CIH-induced cardioprotection. Adult male Wistar rats were exposed to intermittent hypobaric hypoxia (7000 m, 8 h/day, 25 exposures) (n=14) or kept at normoxia (n=14). Half of the animals from each group received N-acetylcysteine (NAC, 100 mg/kg) daily before the hypoxic exposure. The activity and expression of MnSOD were increased by 66 % and 23 %, respectively, in the mitochondrial fraction of CIH hearts as compared with th e normoxic group; these effects were suppressed by NAC treatment. The negative correlation between MnSOD activity and myoc ardial infarct size suggests that MnSOD can contribute to the improved ischemic tolerance of CIH hearts., P. Balková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Our present focus on the hypoxic immature heart is driven by clinical urgency: cyanotic congenital cardiac malformations remain the single largest cause of mortality from congenital defects and ischemic heart disease is no more the disease of the fifth and older decades but its origin as well as risk factors are present already during early ontogeny. Moreover, the number of adult patients operated for cyanotic congenital heart disease during infancy steadily increases. This group approaches the age of the rising risk of serious cardiovascular diseases, particularly ischemic heart disease. Experimental results have clearly shown that the immature heart is significantly more tolerant to oxygen deficiency than the adult myocardium. However, the mechanisms of this difference have not yet been satisfactorily clarified; they are likely the result of developmental changes in cardiac energy metabolism, including mitochondrial function. The high resistance of the newborn heart cannot be further increased by ischemic preconditioning or adaptation to chronic hypoxia; these protective mechanisms appear only with decreasing tolerance during development. Resistance of the adult myocardium to acute oxygen deprivation may be significantly influenced by perinatal hypoxia. These results suggest that the developmental approach offers new possibilities in the studies of pathogenesis, prevention and therapy of critical cardiovascular diseases., B. Ošťádal ... [et al.]., and Obsahuje seznam literatury