Quercetin, a polyphenolic compound present in various types of food, has been shown to exert beneficial effects in different cardiac as well as non-cardiac ischemia/reperfusion (I/R) models in adult animals. However, there is no evidence about the effects of quercetin on I/R injury in non-mature animals, despite the fact that efficiency of some interventions against I/R is age-dependent. This study was aimed to investigate the effects of chronic quercetin treatment on I/R injury in juvenile and adult rat hearts. Juvenile (4-week-old) as well as adult (12-week-old) rats were treated with quercetin (20 mg/kg/day) for 4 weeks, hearts were excised and exposed to 25-min global ischemia followed by 40-min reperfusion. Functional parameters of hearts and occurrence of reperfusion arrhythmias were registered to assess the cardiac function. Our results have shown that quercetin improved post-ischemic recovery of LVDP, as well as recovery of markers of contraction and relaxation, +(dP/dt)max and -(dP/dt)max, respectively, in juvenile hearts, but not in adult hearts. Quercetin had no impact on incidence as well as duration of reperfusion arrhythmias in animals of both ages. We conclude that the age of rats plays an important role in heart response to quercetin treatment in the particular dose and duration of the treatment. Therefore, the age of the treated subjects should be taken into consideration when choosing the dose of quercetin and duration of its application in prevention and/or treatment of cardiovascular diseases.
- MeSH
- antioxidancia terapeutické užití MeSH
- potkani Wistar MeSH
- quercetin terapeutické užití MeSH
- reperfuzní poškození myokardu komplikace prevence a kontrola MeSH
- srdeční arytmie etiologie prevence a kontrola MeSH
- techniky in vitro MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Several studies have shown that diabetes mellitus modulates heart resistance to ischemia and abrogates effectivity of cardioprotective interventions, such as ischemic preconditioning (IP). The aim of this study was to evaluate whether the effect of hyperglycemic conditions on the severity of ischemia-reperfusion (I/R) injury in preconditioned and non-preconditioned hearts (controls, C) is related to changes in osmotic activity of glucose. Experiments were performed in isolated rat hearts perfused according to Langendorff exposed to 30-min coronary occlusion/120-min reperfusion. IP was induced by two cycles of 5-min coronary occlusion/5-min reperfusion, prior to the long-term I/R. Hyperosmotic (HO) state induced by an addition of mannitol (11 mmol/l) to a standard Krebs-Henseleit perfusion medium significantly decreased the size of infarction and also suppressed a release of heart fatty acid binding protein (h-FABP - biomarker of cell injury) from the non-IP hearts nearly to 50 %, in comparison with normoosmotic (NO) mannitol-free perfusion. However, IP in HO conditions significantly increased the size of infarction and tended to elevate the release of h-FABP to the effluent from the heart. The results indicate that HO environment plays a cardioprotective role in the ischemic myocardium. On the other hand, increased osmolarity, similar to that in the hyperglycemic conditions, may play a pivotal role in a failure of IP to induce cardioprotection in the diabetic myocardium.
- MeSH
- buněčné mikroprostředí MeSH
- glukosa - roztok hypertonický farmakologie MeSH
- hyperglykemie patofyziologie MeSH
- infarkt myokardu patologie MeSH
- ischemické přivykání * MeSH
- koronární cirkulace MeSH
- krysa rodu rattus MeSH
- osmolární koncentrace * MeSH
- potkani Wistar MeSH
- reperfuzní poškození myokardu patofyziologie prevence a kontrola MeSH
- srdce patofyziologie MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The aim of our study was to characterize resistance to ischemia/reperfusion (I/R) injury in Langendorff-perfused rat hearts and effectivity of ischemic preconditioning (PC) under condition of simulated acute hyperglycemia (SAHG) by perfusion of the hearts with Krebs-Henseleit (KH) solution with elevated glucose concentration (22 mmol/l). I/R injury was induced by 30-min coronary occlusion followed by 120-min reperfusion and PC by two cycles of 5-min occlusion/5-min reperfusion, prior to I/R. The severity of I/R injury was characterized by determination of the size of infarction (IS, expressed in % of area at risk size) and the amount of heart-type fatty acid binding protein (h-FABP, a marker of cell injury) released from the hearts to the effluent. Significantly smaller IS (8.8+/-1 %) and lower total amount of released h-FABP (1808+/-660 pmol) in PC group compared with IS 17.1+/-1.2 % (p<0.01) and amount of h-FABP (8803+/-2415 pmol, p<0.05) in the non-PC control hearts perfused with standard KH solution (glucose 11 mmol/l) confirmed protective effects of PC. In contrast, in SAHG groups, PC enhanced IS (21.4+/-2.2 vs. 14.3+/-1.3 %, p<0.05) and increased total amount of h-FABP (5541+/-229 vs. 3458+/-283 pmol, p<0.05) compared with respective non-PC controls. Results suggest that PC has negative effect on resistance of the hearts to I/R injury under conditions of elevated glucose in vitro.
- MeSH
- časové faktory MeSH
- funkce levé komory srdeční MeSH
- glukosa metabolismus MeSH
- hyperglykemie komplikace metabolismus MeSH
- infarkt myokardu etiologie metabolismus patologie patofyziologie prevence a kontrola MeSH
- ischemické přivykání * MeSH
- komorový tlak (srdce) MeSH
- modely nemocí na zvířatech MeSH
- myokard metabolismus patologie MeSH
- potkani Wistar MeSH
- proteiny vázající mastné kyseliny metabolismus MeSH
- reperfuzní poškození myokardu etiologie metabolismus patologie patofyziologie prevence a kontrola MeSH
- stupeň závažnosti nemoci MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- financování organizované MeSH
- Publikační typ
- abstrakty MeSH
- MeSH
- financování organizované MeSH
- Publikační typ
- abstrakty MeSH
- MeSH
- financování organizované MeSH
- Publikační typ
- abstrakty MeSH
- MeSH
- financování organizované MeSH
- Publikační typ
- abstrakty MeSH
- MeSH
- financování organizované MeSH
- Publikační typ
- abstrakty MeSH
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 μmol/l) or pravastatin (P, 30 μmol/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 ischemia 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 cardioprotective effects on myocardial stunning and lethal injury induced by ischemia/reperfusion.
- MeSH
- hydrofobní a hydrofilní interakce MeSH
- krysa rodu rattus MeSH
- míra přežití MeSH
- potkani Wistar MeSH
- premedikace metody MeSH
- reperfuzní poškození myokardu komplikace patofyziologie prevence a kontrola MeSH
- srdeční arytmie etiologie patofyziologie prevence a kontrola MeSH
- statiny aplikace a dávkování chemie MeSH
- syndrom omráčeného myokardu etiologie patofyziologie prevence a kontrola MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
