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
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
Risk factors (RF) of cardiovascular diseases associated with modern lifestyle, such as stress, chronically increased blood pressure, hyperglycemia and dyslipidemia have a negative impact on the heart exposed to ischemia: their may facilitate its lethal injury (myocardial infarction) and occurrence of sudden death due to ventricular arrhythmias. On the other hand, some stressful stimuli related to RF including reactive oxygen species, transient episodes of ischemia (hypoxia), high glucose and other may play a dual role in the pathogenesis of ischemia/reperfusion (I/R) injury (IRI). Besides their deleterious effects, these factors may trigger adaptive processes in the heart resulting in greater resistance against IRI, which is also a characteristic feature of the female myocardium. However, sensitivity to ischemia is increasing with age in both genders. Current research indicates that comorbidity related to lifestyle may impair the cardiac response to acute ischemia not only by interference with pathophysiological mechanisms of IRI per se, but via suppression of intrinsic protective mechanisms in the heart and its ability to tolerate the ischemic challenges, although the role of RF has not been unequivocally proven. Moreover, even pathologically altered myocardium need not completely lose its adaptive potential. In addition, increased ischemic tolerance can be induced by the pleiotropic (independent of the primary) effects of some hypolipidemic and antidiabetic drugs, even in the diseased myocardium. This review addresses the issue of the impact of RF on cellular cardioprotective mechanisms and the possibilities to restore adaptive potential in subjects challenged with several RF. Reactivation of adaptive processes in the myocardium taking into consideration gender and age can contribute to optimalization of antiischemic therapy., T. Ravingerová, ... [et al.]., and Obsahuje seznam literatury