Diabetes mellitus je významným rizikovým faktorem pro rozvoj ischemické choroby srdeční. Její prevalence se u diabetiků udává v širokém rozmezí 10–55 %. Po přítomnosti ischemie myokardu je nutno u diabetiků aktivně pátrat, neboť čekání na rozvoj symptomů je u těchto pacientů spojeno s nálezem již pokročilé koronární aterosklerózy s horšími výsledky koronárních intervencí chirurgické léčby. Podle výsledků studie BARDOT se zdá, že vhodným nástrojem pro stratifikaci rizika kardiálních příhod u diabetiků by mohla být zátěžová scintigrafie myokardu. Toto vyšetření dokáže velmi dobře odhalit přítomnost ischemie myokardu, zhodnotit její rozsah i lokalizaci a odlišit, zda jde o reverzibilní ischemii. Tyto údaje jsou velmi důležité pro určení správné strategie léčby. U diabetiků často nalézáme pokročilou koronární aterosklerózu, která je vhodnější k chirurgické léčbě. Nicméně v době moderních stentů je možno i diabetiky léčit intervenčně. Každý́ diabetik by však měl mít důsledně intervenovány všechny ovlivnitelné rizikové faktory ischemické choroby srdeční a měl by být léčen tak zvanou optimální farmakoterapií. Jedná se o medikaci s prokázaným vlivem na prognózu pacientů, ovlivnění progrese koronární aterosklerózy a zmírnění ischemie myokardu., Diabetes mellitus is a major risk factor for the development of ischemic heart disease. Its prevalence in diabetic patients is reported to range broadly between 10–55 %. It is necessary to actively search for the presence of myocardial ischemia in patients with diabetes, since waiting for the development of symptoms is associated with the finding of already advanced coronary atherosclerosis in these patients, with less satisfactory outcomes of coronary interventions and surgery. Results of the BARDOT study seem to indicate that the appropriate tool for stratification of the risk of cardiac events in diabetics could be stress myocardial scintigraphy. This test is successful in detecting the presence of myocardial ischemia, assessing its size and location and identifying whether reversible ischemia is involved. Such data is very important with regard to choosing the right treatment strategy. We often find advanced coronary atherosclerosis in diabetic patients for which surgical treatment is more appropriate. Nonetheless in the era of modern stents also the patients with diabetes can be treated with intervention. All the influenceable risk factors for ischemic heart disease should be consistently treated by intervention in each diabetic patient, who should be given optimum pharmacotherapy. This involves medication with a proven impact on the patient prognosis, influencing the progression of coronary atherosclerosis and mitigation of myocardial ischemia.., and Tomáš Kovárník, Kristýna Bayerová, Karel Kopřiva
Although both lipophilic and more hydrophilic statins share the same pathway of the inhibition of HMG-CoA reductase, their pleiotropic cardioprotective effects associated with the ability to cross cellular membranes, including membranes of heart cells, may differ. To test this hypothesis, isolated rat hearts were Langendorff-perfused either with simvastatin (S, 10 μ mol/l) or pravastatin (P, 30 μ mol/l), 15 min prior to ischemia. Control untreated hearts (C) were perfused with perfusion medium only. Postischemic contractile dysfunction, reperfusion-induced ventricular arrhythmias and infarct size were investigated after exposure of the hearts to 30- min global isch emia and 2-h reperfusion. Both lipophilic S and hydrophilic P reduced the severity of ventricular arrhythmias (arrhythmia score) from 4.3±0.2 in C to 3.0±0 and 2.7±0.2 in S and P, respectively, (both P<0.05), decreased the duration of ventricular tachycardia and suppressed ventricular fibrillation. Likewise, the extent of lethal injury (infarct size) determined by tetrazolium staining and expressed in percentage of risk area, was significantly lower in both treated groups, moreover, the effect of P was more pronounced (27±2 % and 10±2 % in S and P groups, respectively, vs. 42±1 % in C; P<0.05). In contrast, only S, but not P, was able to improve postischemic recovery of left ventricular developed pressure (LVDP; 48±12 % of preischemic values vs. 25±4 % in C and 21± 7 % in P groups; P<0.05). Our results suggest that differences in water solubility of statins indicating a different ability to cross cardiac membranes may underlie their distinct cardioprot ective effects on myocardial stunning and lethal injury induced by ischemia/reperfusion., S. Čarnická ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Thyroid hormones (THs) play multiple roles in the organism and alterations of their levels can result in many pathological changes. Currently, we use hypert hyroid and hypothyroid rats as “models of a diseased organi sm” and analyze whether n-3 polyunsaturated fatty acids (n-3 PUFA) administration can ameliorate TH-induced pathop hysiological changes. We investigate myosin heavy chain composition, calsequestrin levels, changes in cardiac tissue remodeling and cell-to-cell communication, expression of protein kinases, mitochondrial functions, oxidative stress mark ers and cell death, changes in serum lipid levels, activities of key enzymes of thyroid hormone metabolism, activity of acetyl choline esterase and membrane anisotropy, as well as mobile behavior and thermal sensitivity. Additionally we also mention our pilot experiments dealing with the effect of statin administration on skeletal muscles and sensory functions. As THs and n-3 PUFA possess multiple sites of potential action, we hope that our complex research will contribute to a better understanding of their actions, which can be useful in the treatment of di fferent pathophysiological events including cardiac insufficiency in humans., T. Soukup., and Obsahuje bibliografii a bibliografické odkazy
a1_Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are most frequently used drugs in the prevention of coronary artery disease due to their cholesterol- lowering activity. However, it is not exactly known whether these effects of statins or those independent of cholesterol decrease account for the protection ag ainst myocardial ischemia- reperfusion (I/R) injury. In this study, we investigated the effect of 5-day treatment with simvastatin (10 mg/kg) in Langendorff- perfused hearts of healthy control (C) and diabetic- hypercholesterolemic (D-H; strept ozotocin + high fat-cholesterol diet, 5 days) rats subjected to 30-min global ischemia followed by 40-min reperfusion for the examination of postischemic contractile dysfunction and reperfusion-induced ventricular arrhythmias or to 30-min (left anterior descending) coronary artery occlusion and 2-h reperfusion for the infarct size determination (IS; tetrazolium stai ning). Postischemic recovery of left ventricular developed pressu re (LVDP) in animals with D-H was improved by simvastatin therapy (62.7±18.2 % of preischemic values vs. 30.3±5.7 % in the untreated D-H; P<0.05), similar to the values in the simvastatin-treated C group, which were 2.5-fold higher than those in the untreated C group. No ventricular fibrillation occurred in the simvastatin-treated C and D-H animals during reperf usion. Likewise, simvastatin shortened the duration of ventri cular tachycardia (10.2±8.1 s and 57.8±29.3 s in C and D-H vs. 143.6±28.6 s and 159.3±44.3 s in untreated C and D-H, respectively, both P<0.05). The decreased arrhythmogenesis in the simvastatin-treated groups correlated with the limitation of IS (in % of risk area) by 66 % and 62 % in C and D-H groups, respectively. However, simvastatin treatment decreased plasma cholesterol levels neither in the D-H animals nor in C., a2_The results indicate that other effects of statins (independent of cholesterol lowering) are involved in the improvement of contractile recovery and attenuation of lethal I/R injury in both, healthy and diseased individuals., A. Adameová, A. Harčárová, J. Matejíková, D. Pancza, M. Kuželová, S. Čarnická, P. Švec, M. Barteková, J. Styk, T. Ravingerová., and Obsahuje bibliografii
Statin-associated myopathy (SAM) represents a broad spectrum of disorders from insignificant myalgia to fatal rhabdomyolysis. Its frequency ranges from 1-5 % in clinical trials to 15-20 % in everyday clinical practice. To a large extent, these variations can be explained by the definition used. Thus, we propose a scoring system to classify statin-induced myopathy according to clinical and biochemical criteria as 1) possible, 2) probable or 3) definite. The etiology of this disorder remains poorly understood. Most probably, an underlying genetic cause is necessary for overt SAM to develop. Variants in a few gene groups that encode proteins involved in: i) statin metabolism and distribution (e.g. membrane transporters and enzymes; OATP1B1, ABCA1, MRP, CYP3A4), ii) coenzyme Q10 production (e.g. COQ10A and B), iii) energy metabolism of muscle tissue (e.g. PYGM, GAA, CPT2) and several others have been proposed as candidates which can predispose to SAM. Pharmacological properties of individual statin molecules (e.g. lipophilicity, excretion pathways) and patients´ characteristics influence the likelihood of SAM development. This review summarizes current data as well as our own results., M. Vrablik, L. Zlatohlavek, T. Stulc, V. Adamkova, M. Prusikova, L. Schwarzova, J. A. Hubacek, R. Ceska., and Obsahuje bibliografii
Hypertriglyceridemia is an important marker of increased levels of highly atherogenic rem nant -like particles. The importance of lowering plasma levels of triglycerides (TG) has been called into question many times, but currently it is considered an integral part of residual cardiovascular risk reduction strategies. Lifestyle changes (improved diet and increased physical activity) are effective TG lowering measures. Pharmacological treatment usually starts with statins, although associated TG reductions are typically modest. Fibrates are currently the drugs of choice for hyperTG, frequently in c ombination with statins. Niacin and omega -3 fatty acids improve control of triglyceride levels when the above measures are inadequately effective. Some novel therapies including anti- sense oligonucleotides and inhibitors of microsomal triglyceride transfer protein have shown significant TG lowering efficacy. The current approach to the management of hypertriglyceridemia is based on lifestyle changes and, usually, drug combinations (statin and fibrate and/or omega -3 fatty acids or niacin)., M. Vrablík, R. Češka., and Obsahuje bibliografii