Considering the effects of alcohol on cardiac electrical behavior as well as the important role of the inward rectifier potassium current I K1 in arrhythmogenesis, this study was aimed at the effect of acetaldehyd e, the primary metabolite of ethanol, on I K1 in rat ventricular myocytes. Acetaldehyde induced a reversible inhibition of I K1 with IC 50 = 53.7± 7.7 μM at -110 mV; a significant inhibition was documented even at clinically -relevant concentrations (at 3 μM by 13.1 ±3.0 % ). The inhibition was voltage -independent at physiological voltages above - 90 mV. The I K1 changes under acetaldehyde may contribute to alcohol - induced alterations of cardiac electrophysiology, especially in individuals with a genetic defect of a ldehyde dehydrogenase where the acetaldehyde level may be elevated., M. Bébarová, P. Matejovič, M. Šimurdová, J. Šimurda., and Obsahuje bibliografii
Our aim was to test the hypothesis that the occurrence of extrasystoles in higher decennia is proportional to the altitude. The occurrence of supraventricular (SVPB) and ventricular (VEB) extrasystoles, values of systolic and diastolic blood pressure and the heart rate were studied in 20 healthy elderly men (50-64 years) during cable cabin transportation to a moderate altitude. These values were measured in stations located at 898 m, 1764 m, and 2632 m above sea level during the transportation in both directions. Our records show that the values of blood pressure and heart rate were within normal limits during the whole period of transportation. Both SVPB and VEB were increasing during the ascent and decreasing to the initial values during the descent compared to the values at altitude of 898 m. The highest values (6 to 7-times exceeding the initial ones) were measured at the summit. The results have demonstrated that the occurrence of SVPB and VEB is proportional to the altitude. The increased incidence in the number of extrasystoles is suggested to be mediated by beta-adrenoceptors., Š. Kujaník, M. Sninčák, K. Galajdová, K. Racková., 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
Gap junction connexin channels are important determinants of myocardial conduction and synchronization that is crucial for coordinated heart function. One of the main risk factors for cardiovascular events that results in heart attack, congestive heart failure, stroke as well as sudden arrhythmic death is hypertension. Mislocalization and/or dysfunction of specific connexin-43 channels due to hypertension-induced myocardial remodeling have been implicated in the occurrence of lifethreatening arrhythmias and heart failure in both, humans as well as experimental animals. Recent studies suggest that downregulation of myocardial connexin-43, its abnormal distribution and/or phosphorylation might be implicated in this process. On the other hand, treatment of hypertensive animals with cardioprotective drugs (e.g. statins) or supplementation with non-pharmacological compounds, such as melatonin, omega-3 fatty acids and red palm oil protects from lethal arrhythmias. The antiarrhythmic effects are attributed to the attenuation of myocardial connexin-43 abnormalities associated with preservation of myocardial architecture and improvement of cardiac conduction. Findings uncover novel mechanisms of cardioprotective (antihypertensive and antiarrhythmic) effects of compounds that are used in clinical settings. Well-designed trials are needed to explore the antiarrhythmic potential of these compounds in patients suffering from hypertension., T. Egan Benova, B. Szeiffova Bacova, C. Viczenczova, E. Diez, M. Barancik, N. Tribulova., and Obsahuje bibliografii
We examined the involvement of phosphatidylinositol 3-kinase (PI3K) and its effector protein ki nase B (Akt) in cardioprotective effects of ischemic preconditioning (PC) with particular regards to its role in the protection against ischemia-induced arrhythmias in isolated perfused rat heart. PI3K/Akt inhibitor wortmannin (100 nM) was administered 15 min prior to 30-min regional (left anterior descending coronary artery occlusion) ischemia for the study of ischemic arrhythmias in the hearts perfused at constant coronary flow or prior to 30-min global ischemia followed by 2-h reperfusion for the infarct size (IS) determination (tetrazolium staining) in the hearts perfused at constant pressure. PC procedure (one cycle of isch emia/reperfusion, 5 min each) significantly reduced the total number of ventricular premature complexes (PVC) and severity of arrhythmias (arrhythmia score; AS) over the whole period of left anterior descending coronary artery occlusion in comparison with non-PC controls (PVC 166±40; AS 1.6±0.2 vs . 550±60 and 3.2±0.2; respectively; P<0.05). In a setting of global ischemia/reperfusion, PC decreased IS (in % of the left ventricle, LV) by 73 %. Pretreatment with wortmannin modified neither arrhythmogenesis nor IS in the non-PC hearts. Bracketing of PC with wortmannin did not abolish antiarrhythmic protection (PVC 92±25; AS 1.7±0.2; P<0.05 vs . non-PC hearts). On the other hand, wortmannin increased IS/LV in the PC hearts to 24±1.2 % as compared with 9 ± 0.6 % in the untreated ones (P<0.05). In conclusion, PI3K/Akt inhibition did not affect reduced arrhythmogenesis during ischemia in the PC hearts indicating that in contrast to its positive role in the irreversible myocardial injury, PI3K/Akt activity is not required for protection induced by PC against ischemic arrhythmias in the rat heart., T. Ravingerová, J. Matejíková, D. Pancza, F. Kolář., and Obsahuje bibliografii
The effect of three-day fasting on cardiac ischemic tolerance was investigated in adult male Wistar rats. Anesthetized open-chest animals (pentobarbitone 60 mg/kg, i.p.) were subjected to 20-min left anterior descending coronary artery occlusion and 3-h reperfusion for infarct size determination. Ventricular arrhythmias were monitored during ischemia and at the beginning (3 min) of reperfusion. Myocardial concentrations of beta-hydroxybutyrate and acetoacetate were measured to assess mitochondrial redox state. Short-term fasting limited the infarct size (48.5±3.3 % of the area at risk) compared to controls (74.3±2.2 %) and reduced the total number of premature ventricular complexes (12.5±5.8) compared to controls (194.9±21.9) as well as the duration of ventricular tachycardia (0.6±0.4 s vs. 18.8±2.5 s) occurring at early reperfusion. Additionally, fasting increased the concentration of beta-hydroxybutyrate and betahydroxybutyrate/acetoacetate ratio (87.8±27.0) compared to controls (7.9±1.7), reflecting altered mitochondrial redox state. It is concluded that three-day fasting effectively protected rat hearts against major endpoints of acute I/R injury. Further studies are needed to find out whether these beneficial effects can be linked to altered mitochondrial redox state resulting from increased ketogenesis., M. Šnorek ... [et al.]., and Obsahuje seznam literatury
Diabetic heart is suggested to exhibit either increased or decreased resistance to ischemic injury. Ischemic preconditioning suppresses arrhythmias in the normal heart, whereas relatively little is known about its effects in the diseased myocardium. Our objective was to investigate whether development of diabetes mellitus modifies the susceptibility to ischemia-induced arrhythmias and affects preconditioning in the rat heart. Following 1 and 9 weeks of streptozotocin-induced (45 mg/kg, i.v.) diabetes, the hearts were Langendorff-perfused at constant pressure of 70 mm Hg and subjected to test ischemia induced by 30 min occlusion of the left anterior descending (LAD) coronary artery. Preconditioning consisted of one cycle of 5 min ischemia and 10 min reperfusion, prior to test ischemia. Susceptibility to ischemia-induced arrhythmias was lower in 1-week diabetics: only 42 % of diabetic hearts exhibited ventricular tachycardia (VT) and 16 % had short episodes of ventricular fibrillation (VF) as compared to VT 100 % and VF 70 % (including sustained VF 36 %) in the non-diabetics (P<0.05). Development of the disease was associated with an increased incidence of VT (VT 92 %, not significantly different from non-diabetics) and longer total duration of VT and VF at 9-weeks, as compared to 1-week diabetics. Preconditioning effectively suppressed arrhythmias in the normal hearts (VT 33 %, VF 0 %). However, it did not provide any additional antiarrhythmic protection in the acute diabetes. On the other hand, in the preconditioned 9-weeks diabetic hearts, the incidence of arrhythmias tended to decrease (VT 50 %, transient VF 10 %) and their severity was reduced. Diabetic rat hearts are thus less susceptible to ischemia-induced arrhythmias in the acute phase of the disease. Development of diabetes attenuates increased ischemic tolerance, however, diabetic hearts in the chronic phase can benefit more from ischem preconditioning, due to its persisting influence., T. Ravingerová, R. Štetka, D. Pancza, O. Uličná, A. Ziegelhöffer, J. Styk., and Obsahuje bibliografii