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
AMP -activated protein kinase (AMPK) plays a role in metabolic regulation under stress conditions, and inadequate AMPK signaling may be also involved in aging process. The aim was to find out whether AMPK α 2-subunit deletion affects heart function and ische mic tolerance of adult and aged mice. AMPK α 2 -/- (KO) and wild type (WT) female mice were compared at the age of 6 and 18 months. KO mice exhibited subtle myocardial AMPK α 2-subunit protein level, but no difference in AMPK α 1-subunit was detected between the strains. Both α 1- and α 2-subunits of AMPK and their phosphorylation decreased with advanced age. Left ventricular fractional shortening was lower in KO than in WT mice of both age groups and this difference was maintained after high-fat feeding. Infarct size induced by global ischemia/reperfusion of isolated hearts was similar in both strains at 6 months of age. Aged WT but not KO mice exhibited improved ischemic tolerance compared with the younger group. High-fat feeding for 6 months during aging abolished the infarct size-reduction in WT without affecting KO animals; nevertheless, the extent of injury remained larger in KO mice. The results demonstrate that adverse effects of AMPK α 2-subunit deletion and high-fat feeding on heart function and myocardia l ischemic tolerance in aged female mice are not additive., K. Slámová, F. Papoušek, P. Janovská, J. Kopecký, F. Kolář., and Obsahuje bibliografii
The consequences of increased oxidative stress, measured as the level of malondialdehyde (MDA) during ischemia/reperfusion, were studied in 48 patients in the acute phase of myocardial infarction (AMI) and a control group (21 blood donors). The serum levels of a-tocopherol and b-carotene were followed. Immediately after the treatment onset the level of a-tocopherol started to decrease, reaching a plateau after 24 h. The consumption of b-carotene was delayed by 90 min. Steady decline was detected during the whole time interval studied (48 h). Glutathione peroxidase (GPx) activity, as a representative of antioxidant enzymes, was estimated in whole blood. The influx of oxygenated blood was accompanied by a stimulation of GPx activity, which reached its maximum at the time of completed reperfusion. When comparing the AMI patients with the control group, the levels of MDA were found significantly increased, which indicates that oxidative stress is already increased during ischemia. Lower antioxidant levels found in the patients might either already be the result of vitamin consumption during ischemia or be a manifestation of their susceptibility to AMI. Monitored consumption of a-tocopherol and b-carotene during reperfusion indicated that in the case of patients, whose level of antioxidant vitamins is below the threshold limit, a further substantial decrease of antioxidant vitamins during reperfusion could enhance the oxidative damage of the myocardium., V. Mužáková, R. Kanďár, P. Vojtíšek, J. Skalický, R. Vaňková, A. Čegan, Z. Červinková., and Obsahuje bibliografii
High plasma levels of triglycerides (TG) are an independent risk factor in the development of cardiovascular disease, with about 50 % of the final levels being determined genetically. Apolipoprotein A5 ( APOA5 ) is the last discovered member of the apolipoprotein APOA1/C3/A4 gene cluster, found by comparative sequencing analysis. The importance of APOA5 gene for determination of plasma triglyceride levels has been suggested after development of transgenic and knock-out mice (transgenic mice displayed significantly reduced TG, whereas knock-out mice had high TG). In Czech population, alleles C-1131 and Trp19 are associated with elevated levels of plasma TG and higher risk of myocardial infarction development. These alleles also play some role in nutrigenetics and actigenetics of lifestyle interventions leading to the plasma cholesterol changes as well as in the pharmacogenetics of statin treatment. On the contrary, APOA5 mutations detected in Czech population did not show strict effect on plasma TG levels. Val153 → Met variant exhibit the sex-specific effect of HDL-cholesterol levels. The suggested roles of APOA5 variants in determination of the plasma remnant particles, plasma concentrations of C-reactive protein or some anthropometrical parameters were excluded., J. A. Hubáček ... [et al.]., and Obsahuje seznam literatury
Sympathetic overactivity and low parasympathetic activity is an autonomic dysfunction (AD) which enhances cardiac mortality. In the present study, the impact of AD on the mortality in patients after myocardial infarction was evaluated. We examined 162 patients 7-21 days after myocardial infarction, 20 patients of whom died in the course of two years. Baroreflex sensitivity (BRS) was estimated by spectral analysis of spontaneous fluctuations of systolic blood pressure and cardiac intervals (Finapres, 5 min recording, controlled breathing 20/min). The heart rate variability was determined as SDNN index (mean of standard deviations of RR intervals for all 5-min segments of 24-hour ECG recordings). BRS < 3 ms/mm Hg and/or SDNN index < 30 ms were taken as markers of AD. The risk stratification was performed according to the number of the following standard risk factors of increased risk of cardiac mortality (SRF): ejection fraction < 40 %, positive late potentials and the presence of ventricular extrasystoles > 10/h. No difference in mortality between patients with AD (4 %) and without AD (4.5 %) was found in 92 patients without SRF, the mortality in 6 patients with three SRF was 66.6 %. Five of these patients had AD. Out of 64 patients with one or two SRF, 32 had AD. The mortality of patients without AD was 6.25 % and 31.2 % of those with AD (p<0.025). It is concluded that AD enhanced two-years mortality five fold in our patients with moderate risks., N. Honzíková, B. Semrád, B. Fišer, R. Lábrová., and Obsahuje bibliografii
In order to examine the relationship between certain risk factors for atherosclerosis and family history of myocardial infarction, we compared a group of children (n=51) whose parents had survived myocardial infarction (n=34) with a control group of children (n=90) with a negative family history of atherosclerosis (62 parents). The study revealed a surprising fact that 26.7 % of control children had hypercholesterolaemia compared to 15.7 % incidence in "risk" children. "Risk" children differed from the controls most in the apo-A-l levels and a higher risk index expressed by the proportion of apo-B:apo-A-l (1.22, 1.34 g/1, p=0.001, 0.58, 0.46, p=0.05, respectively). Since the most frequent primary hyperlipoproteinaemia in myocardial infarction families was familial combined hyperlipoproteinaemia, we assume that this condition may be presented in affected children by an unfavourable proportion of apolipoproteins of the lipoprotein classes.
Exercise can improve the cardiovascular health. However, the mechanism contributing to its beneficial effect on elderly patients with myocardial infarction is obscure. 20-month-old male Sprague-Dawley rats were used to establish myocardial infarction (MI) model by permanent ligation of the left anterior descending coronary artery (LAD) of the heart, followed by 4-week interval exercise training on a motor-driven rodent treadmill. The cardiac function, myocardial fibrosis, apoptosis, oxidative stress, and inflammatory responses were determined by using pressure transducer catheter, polygraph physiological data acquisition system, Masson's trichrome staining, and ELISA to evaluate the impact of post-MI exercise training on MI. Western blot were performed to detect the activation of AMPK/SIRT1/PGC-1α signaling in the hearts of aged rats. Exercise training significantly improved cardiac function and reduced the cardiac fibrosis. In infarcted heart, the apoptosis, oxidative stress, and inflammation were significantly reduced after 4-week exercise training. Mechanistically, AMPK/SIRT1/PGC-1α pathway was activated in the myocardial infarction area after exercise training, which might participate in the protection of cardiac function. Exercise training improves cardiac function in MI rats through reduction of apoptosis, oxidative stress, and inflammation, which may mediate by the activation of AMPK/SIRT1/PGC-1α signaling pathway.
The aim of the present study was to explore whether hydrogen sulfide (H2S) protects against ischemic heart failure (HF) by inhibiting the necroptosis pathway. Mice were randomized into Sham, myocardial infarction (MI), MI + propargylglycine (PAG) and MI + sodium hydrosulfide (NaHS) group, respectively. The MI model was induced by ligating the left anterior descending coronary artery. PAG was intraperitoneally administered at a dose of 50 mg/kg/day for 4 weeks, and NaHS at a dose of 4mg/kg/day for the same period. At 4 weeks after MI, the following were observed: A significant decrease in the cardiac function, as evidenced by a decline in ejection fraction (EF) and fractional shortening (FS), an increase in plasma myocardial injury markers, such as creatine kinase-MB (CK-MB) and cardiac troponin I (cTNI), an increase in myocardial collagen content in the heart tissues, and a decrease of H2S level in plasma and heart tissues. Furthermore, the expression levels of necroptosis-related markers such as receptor interacting protein kinase 1 (RIP1), RIP3 and mixed lineage kinase domain-like protein (MLKL) were upregulated after MI. NaHS treatment increased H2S levels in plasma and heart tissues, preserving the cardiac function by increasing EF and FS, decreasing plasma CK-MB and cTNI and reducing collagen content. Additionally, NaHS treatment significantly downregulated the RIP1/RIP3/MLKL pathway. While, PAG treatment aggravated cardiac function by activated the RIP1/RIP3/MLKL pathway. Overall, the present study concluded that H2S protected against ischemic HF by inhibiting RIP1/RIP3/MLKL-mediated necroptosis which could be a potential target treatment for ischemic HF.
Endothelin alters central sympathetic responses, but the resultant effects on arrhythmogenesis are unknown. We examined ventricular tachyarrhythmias after endothelin receptor-A blockade in the brain of Wistar rats with acute myocardial infarction. For this aim, BQ-123 (n=6) or phosphate-buffered saline (n=6) were injected intracerebroventricularly. After 10 min, the left coronary artery was ligated, followed by implantation of telemetry transmitters. Electrocardiography and voluntary activity (as a surrogate of acute left ventricular failure) were continuously monitored for 24 h. Infarct-size was similar in the two groups. There were fewer episodes of ventricular tachyarrhythmias of shorter average duration in treated rats, leading to markedly shorter total duration (12.3±8.9 s), when compared to controls (546.2±130.3 s). Voluntary activity increased in treated rats during the last hours of recording, but bradyarrhythmic episodes were comparable between the two groups. Endothelin receptor-A blockade in the brain of rats decreases the incidence of ventricular tachyarrhythmias post-ligation, without affecting bradyarrhythmic episodes. These findings call for further research on the pathophysiologic role of endothelin during acute myocardial infarction.