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
Akutní koronárni syndrom je velmi důležitou oblastí současně akutní a invazivní kardiológie. Ve stáří je doprovážen řadou dalších závažných onemocnění, která ovlivňují průběh nemoci i prognózu; obvyklý je i netypický průběh nemoci. Autor stručně vymezuje AKS obecně, zvláštní oddíl věnuje problematice onemocnění ve stáří., Acute coronary syndrome (ACS) is a very important domain of contemporary acute and invasive cardiology. Many severe concomitant disorders influence the progress and prognosis of the disease; an unusual progress of the illness is also common. The author specifies ACS in general, a special part is dedicated to ACS in elderly., Petr Kala, Martin Poloczek, and Lit. 34
Sekundární prevence aterotrombotických příhod je doménou protidestičkové léčby, podle rizika jedním lékem či kombinací acetylsalicylové kyseliny s blokátory ADP receptorů. Význam kombinace duální protidestičkové léčby v kombinaci s xabany či s dabigatranem prověřovalo 6 klinických studií. Pouze jedna z nich (ATLAS ACS 2-TIMI 51) ukázala, že léčba malými dávkami rivaroxabanu (2krát 2,5 mg) může být přidána ke kombinaci kyseliny acetylsalicylové s klopidogrelem. Pro několikanásobně zvýšené riziko velkých krvácivých příhod se však čistý klinický přínos pohybuje jen kolem 0,5 % ročně. Duální léčba s kombinací kyseliny acetylsalicylové s prasugrelem či s tikagrelorem je přínosnější. V druhé části přehledu je rozebírán vyšší výskyt infarktu myokardu v kontrolovaných studiích při léčbě dabigatranem v porovnání s warfarinem. Vztah není dořešen, nicméně u nemocných s vyšším rizikem koronárních příhod je při indikaci antikoagulační léčby přímými antikoagulancii vhodnější volit ze skupiny xabanů (apixaban či rivaroxaban)., Secondary prevention of atherothrombotic events is the domain of antiplatelet therapy and according to present risk is used one drug strategy or combination of acetylsalicylic acid with ADP receptor blockers. The importance of the combination of dual antiplatelet therapy together with xabans or dabigatran was investigated in 6 clinical trials. Only one of them (ATLAS ACS 2-TIMI 51) indicated that treatment with small dose of rivaroxaban (2 × 2.5 mg) may be added to dual strategy of acetylsalicylic acid and clopidogrel. The risk of major bleeding event is increased and net clinical benefit is only about 0.5 % per year. Dual therapy with aspirin and prasugrel or tikagrelor is beneficial. In the second part of the review is discussed higher incidence of myocardial infarction in controlled group in the trial comparing treatment of dabigatran with warfarin. This relationship has not been resolved, however, in patients with higher risk of coronary events and indication of anticoagulant treatment with direct oral anticoagulants it is recommended to choose from xabans (apixaban and rivaroxaban)., and Jan Bultas
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
The aim of this study was a comparison of risk stratification for death in patients after myocardial infarction (MI) and of risk stratification for malignant arrhythmias in patients with implantable cardioverter-defibrillator (ICD). The individual risk factors and more complex approaches were used, which take into account that a borderline between a risky and non-risky value of each predictor is not clear-cut (fuzzification of a critical value) and that individual risk factors have different weight (area under receiver operating curve - AUC or Sommers´ D - Dxy). The risk factors were baroreflex sensitivity, ejection fraction and the number of ventricular premature complexes/hour on Holter monitoring. Those factors were evaluated separately and they were involved into logit model and fuzzy models (Fuzzy, Fuzzy-AUC, and Fuzzy-Dxy). Two groups of patients were examined: a) 308 patients 7-21 days after MI (23 patients died within period of 24 month); b) 53 patients with left ventricular dysfunction examined before implantation of ICD (7 patients with malignant arrhythmia and electric discharge within 11 month after implantation). Our results obtained in MI patients demonstrated that the application of logit and fuzzy models was superior over the risk stratification based on algorithm where the decision making is dependent on one parameter. In patients with implanted defibrillator only logit method yielded statistically significant result, but its reliability was doubtful because all other tests were statistically insignificant. We recommend evaluating the data not only by tests based on logit model but also by tests based on fuzzy models., P. Honzík ... [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
Acute myocardial infarction (AMI) is one of the leading causes of death among adults in older age. Understanding mechanisms how organism responds to ischemia is essential for the ischemic patient’s prevention and treatment. Despite the great prevalence and incidence only a small number of studies utilize a metabolomic approach to describe AMI condition. Recent studies have shown the impact of metabolites on epigenetic changes, in these studies plasma metabolites were related to neurological outcome of the patients making metabolomic studies increasingly interesting. The aim of this study was to describe metabolomic response of an organism to ischemic stress through the changes in energetic metabolites and aminoacids in blood plasma in patients overcoming acute myocardial infarction. Blood plasma from patients in the first 12 h after onset of chest pain was collected and compared with volunteers without any history of ischemic diseases via NMR spectroscopy. Lowered plasma levels of pyruvate, alanine, glutamine and neurotransmitter precursors tyrosine and tryptophan were found. Further, we observed increased plasma levels of 3-hydroxybutyrate and acetoacetate in balance with decreased level of lipoproteins fraction, suggesting the ongoing ketonic state of an organism. Discriminatory analysis showed very promising performance where compounds: lipoproteins, alanine, pyruvate, glutamine, tryptophan and 3-hydroxybutyrate were of the highest discriminatory power with feasibility of successful statistical discrimination., Martin Petras, Dagmar Kalenska, Matej Samos, Tomas Bolek, Miroslava Sarlinova, Peter Racay, Erika Halasova, Oliver Štrbák, Jan Stasko, Ludovit Musak, Michaela Skorvanova, Eva Baranovicova., and Obsahuje bibliografii
Adaptation to hypoxia is beneficial in cardiovascular pathology related to NO shortage or overproduction. However, the question about the influence of adaptation to hypoxia on NO metabolism has remained open. The present work was aimed at the relationship between processes of NO production and storage during adaptation to hypoxia and the possible protective significance of these processes. Rats were adapted to intermittent hypobaric hypoxia in an altitude chamber. NO production was determined by plasma nitrite/nitrate level. Vascular NO stores were evaluated by relaxation of the isolated aorta to diethyldithiocarbamate. Experimental myocardial infarction was used as a model of NO overproduction; stroke-prone spontaneously hypertensive rats (SHR-SP) were used as a model of NO shortage. During adaptation to hypoxia, the plasma nitrite/nitrate level progressively increased and was correlated with the increase in NO stores. Adaptation to hypoxia prevented the excessive endothelium-dependent relaxation and hypotension characteristic for myocardial infarction. At the same time, the adaptation attenuated the increase in blood pressure and prevented the impairment of endothelium-dependent relaxation in SHR-SP. The data suggest that NO stores induced by adaptation to hypoxia can either bind excessive NO to protect the organism against NO overproduction or provide a NO reserve to be used in NO deficiency., E. B. Manukhina, S. Yu. Mashina, B. V. Smirin, N. P. Lyamina, V. N. Senchikhin, A. F. Vanin, I. Yu. Malyshev., and Obsahuje bibliografii