The effect of the chronic and acute antioxidant tempol (superoxide dismutase mimetic) treatment on cardiac ischemic tolerance was investigated in adult male Wistar rats. The first experimental group was given tempol (1 mM) in drinking water for three weeks, the second group received tempol (100 mg/kg, i.v.) 10 min before test ischemia, and control rats received the same volume of solvent. Anesthetized open-chest animals (pentobarbitone 60 mg/kg, i.p.) were subjected to 20-min coronary artery occlusion and 3-h reperfusion for infarct size determination. Ventricular arrhythmias were monitored during ischemia and at the beginning (5 min) of reperfusion. Acute tempol administration shifted the time profile of ischemic arrhythmias to the later phase and significantly increased the number of ischemic and reperfusion premature ventricular complexes, respectively (504±127 and 84±21) as compared with the chronically treated group (218±36 and 47±7) or controls (197±26 and 31±7). Acute tempol-treated rats exhibited a tendency to decrease infarct size (P = 0.087). The mechanism of proarrhythmic tempol action during ischemia and reperfusion remains to be elucidated., J. Neckář, B. Ošťádal, F. Kolář., and Obsahuje bibliografii a bibliografické odkazy
The effect of chronic hypercapnia on cardioprotection induced by chronic hypoxia was investigated in adult male Wistar rats exposed to isobaric hypoxia (10 % O2) for three weeks. In the first experimental group, CO2 in the chamber was fully absorbed; in the second group, its level was increased to 4.1 %. Normoxic controls were kept in atmospheric air. Anesthetized open-chest animals were subjected to 20-min LAD coronary artery occlusion and 3-h reperfusion for infarct size determination (TTC staining). Chronic hypoxia alone reduced body weight and increased hematocrit; these effects were significantly attenuated by hypercapnia. The infarct size was reduced from 61.9 ± 2.2 % of the area at risk in the normoxic controls to 44.5±3.3 % in the hypoxic group (P<0.05). Hypercapnia blunted the infarct size-limiting effect of hypoxia (54.8±2.4 %; P<0.05). It is concluded that increased CO2 levels in the inspired air suppress the development of the chronic hypoxia-induced cardioprotective mechanism, possibly by interacting with ROS signalling pathways., J. Neckář, O. Szárszoi, J. Herget, B. Ošťádal, F. Kolář., and Obsahuje bibliografii
Statins are powerful lipid-lowering drugs, widely used in patients with hyperlipidemia and coronary artery disease. It was found, however, that statins appear to have a pleiotropic effect beyond their lipid-lowering ability. They exert anti-inflammatory, antithrombotic and antioxidant effects, increase nitric oxide production and improve endothelial dysfunction. The aim of our study was to examine the effect of chronic and acute treatment with simvastatin on the contractile function of the isolated perfused rat heart after ischemia/reperfusion injury. Contractile function was measured on isolated rat hearts, perfused according to Langendorff under constant pressure. The hearts were subjected to 20 min of global ischemia, followed by 40 min of reperfusion. To investigate the acute effect, simvastatin at a concentration of 10 μmol/l was added to the perfusion solution during reperfusion. In chronic experiments the rats were fed simvastatin at a concentration of 10 mg/kg for two weeks before the measurement of the contractile function. Acute simvastatin administration significantly increased reparation of the peak of pressure development [(+dP/dt)max] (52.9±8.2 %) after global ischemia, as compared with the control group (28.8±5.2 %). Similar differences were also observed in the time course of the recovery of [(+dP/dt)max]. Chronic simvastatin was without any protective effect. Our results reveal that the acute administration of simvastatin during reperfusion, unlike the chronic treatment, significantly reduced contractile dysfunction induced by ischemia/reperfusion injury. This supports the idea of possible cardioprotective effect of statin administration in the first-line therapy of the acute coronary syndrome., O. Szárszoi, J. Malý, P. Ošťádal, I. Netuka, J. Bešík, F. Kolář, B. Ošťádal., and Obsahuje bibliografii a bibliografické odkazy
Hypoxia has been identified as an important stimulus for gene expression during embryogenesis and in various pathological situations. Its influence under physiological conditions, however, has only been studied occasionally. We therefore investigated the effect of intermittent high altitude hypoxia on the mRNA expression of different cytokines and protooncogenes, but also of other genes described to be regulated by hypoxia, in the left ventricle (LV), the right ventricle (RV), atria and the lung of adult rats after simulation of hypoxia in a barochamber (5000 m, 4 hours to 10 days). Heme oxygenase-1 as well as transforming growth factor-β1 showed an increased expression in all regions of the heart and the lung at different periods of hypoxia. For lactate dehydrogenase-A, we found a significant up-regulation in the RV and the lung, for lactate dehydrogenase-B up-regulation in the RV, but down-regulation in the LV and the atria. Vascular endothelial growth factor was up-regulated in the RV, the LV and the lung, but down-regulated in the atria. Its receptor Flk-1 mRNA was significantly increased in the atria and RV only. Expression of c-fos was found in the LV and RV only after 4 hours of hypoxia. The level of c-jun was significantly increased in the LV but decreased in the atria. Our data clearly demonstrate that intermittent hypoxia is a modulator of gene expression under physiological conditions. It differently regulates the expression of distinct genes not only in individual organs but even within one organ, i.e. in the heart., E. Deindl, F. Kolář, E. Neubauer, S Vogel, W. Schaper, B. Ošťádal., and Obsahuje bibliografii
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
Normal increase in hemodynamic load during early postnatal life is associated with heart growth and maturation of membrane structures that is accompanied by remodeling of membrane protein and lipid components. This review describes remodeling of phospholipids (PL) in rat myocardium during normal postnatal development and during accelerated cardiac growth induced by additional workload (aorta constriction, chronic hypoxia and hyperthyroidism) imposed on the heart early after birth. Normal physiological load after birth stimulates the development of membrane structures and synthesis of PL. While hyperthyroidism accelerates these processes, pressure overload has an inhibitory effect. These changes primarily influence the maturation of mitochondrial membranes as cardiolipin is one of the most affected PL species. The most sensitive part of PL structure in their remodeling process are PL acyl chains, particularly polyunsaturated fatty acids that are the key components determining the basic physicochemical properties of the membrane bilayer and thus the function of membrane-bound proteins and membrane-derived signaling lipid molecules. It is evident that PL remodeling may significantly influence both normal and pathological postnatal development of myocardium., F. Novák ... [et al.]., and Obsahuje seznam literatury
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
Inhalational anesthetic-induced preconditioning (APC) has been shown to reduce infarct size and attenuate contractile dysfunction caused by myocardial ischemia. Only a few studies have reported the effects of APC on arrhythmias during myocardial ischemia-reperfusion injury, focusing exclusively on reperfusion. Accordingly, the ai m of the present study was to examine the influence of APC on ventricular arrhythmias evoked by regional no-flow ischemia. APC was induced in adult male Wistar rats by 12-min exposures to two different concentrations (0.5 and 1.0 MAC) of isoflurane followed by 30-min wash-out periods. Ventricular arrhythmias were assessed in the isolated perfused hearts during a 45- min regional ischemia and a subsequent 15-min reperfusion. Myocardial infarct size was determined after an additional 45 min of reperfusion. The incidence, severity and duration of ventricular arrhythmias during ischemia were markedly reduced by APC. The higher concentration of isoflurane had a larger effect on the incidence of ventricular fibrillation than the lower concentration. The incidence of ventricular tachycardia and reversible ventricular fibrillation during reperfusion was also significantly reduced by APC; the same was true for myocardial infarct size. In conclusion, we have shown that preconditioning with isoflurane confers profound protection against myocardial is chemia- and reperfusion-induced arrhythmias and lethal myocardial injury., H. Říha ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Clinical and experimental studies have repeatedly indicated that overloaded hearts have a higher vulnerability to ischemia/reperfusion injury. The aim of the present study was to answer the question whether the degree of tolerance to oxygen deprivation in hearts of spontaneously hypertensive rats (SHR) may be sex-dependent. For this purpose, adult SHR and their normotensive control Wistar Kyoto (WKY) rats were used. The isolated hearts were perfused according to Langendorff at constant pressure (proportionally adjusted to the blood pressure in vivo). Recovery of contractile parameters (left ventricular systolic, diastolic and developed pressure as well as the peak rate of developed pressure) was measured during reperfusion after 20 min of global no-flow ischemia in 5 min intervals. Mean arterial blood pressure was measured by direct puncture of carotid artery under light ether anesthesia in a separate group of animals. The degree of hypertension was comparable in both sexes of SHR. The recovery of contractile functions in SHR males and females was significantly lower than in WKY rats during the whole investigated period. There was no sex difference in the recovery of WKY animals; on the other hand, the recovery was significantly better in SHR females than in SHR males. It may be concluded that the hearts of female SHR are more resistant to ischemia/reperfusion injury as compared with male SHR. This fact could have important clinical implications for the treatment of cardiovascular disease in women., J. Bešík, O. Szárszoi, J. Kuneš, I. Netuka, J. Malý, F. Kolář, J. Pirk, B. Ošťádal., and Obsahuje bibliografii a bibliografické odkazy