Ischemia/Reperfusion-induced injury in the myocardium: mechanism and prevention
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In summary, our data provide evidence that the development of reperfusioninduced VF inhibits HO-1 mRNA expression and enzyme activity in both electrically fibrillated myocardium and ischemic and reperfused fibrillated hearts. The results clearly show that HO-1 mRNA expression and enzyme activity were increased in ischemic and reperfused nonfibrillated myocardium suggesting that interventions which are able to increase HO-1 mRNA expression and enzyme activity may prevent the development of VF. Furthermore in the studies presented in this part of my thesis, superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were characterized in isolated perfused hearts of 18-month-old SHR and the age-matched normotensive control Wistar-Kyoto rats (WKY), before and after 30 min infusion of 25 μM H2O2. The results obtained in ischemic and reperfused hearts show the same changes in enzyme activities measured as it was observed in H2O2 perfused hearts, indicating that oxidative stress is independent of the way it was induced. The higher catalase activity derived from elevated mRNA synthesis. The antioxidative system in dilative cardiomyopathic hearts of SHR is induced, probably due to episodes of oxidative stress, during the process of decompensation. This conditioning of the antioxidative poten-tial may help overcome acute stress situations caused by reactive oxygen species in the failing myocardium. In the last part of my studies the effects of red grape seed proanthocyanidins were studied on the recovery of postischemic function in isolated rat hearts. In rats treated with 50 and 100 mg/kg of grape seed proanthocyanidins, the incidence of reperfusion-induced VF was reduced from its control value of 92% to 42% (p<0.05) and 25% (p<0.05), respectively. The incidence of ventricular tachycardia (VT) showed the same pattern. In rats treated with 100 mg/kg proanthocyanidins, after 60 min reperfusion, the recovery of coronary flow, aortic flow, and developed pressure was improved by 32% ± 8% (p<0.05), 98% ± 8% (p<0.05), 37% ± 3% (p<0.05), respectively, compared to the drug-free controls. ESR studies indicate that proanthocyanidins significantly inhibited the formation of oxygen free radicals. In rats treated with 100 mg/kg of proanthocyanidins, free radical intensity was reduced by 75% ± 7% (p<0.05) compared to the drug-free value. Grape seed proanthocyanidins possess cardioprotective effect against reperfusioninduced injury through their abilities to reduce or remove, directly or indirectly, free radicals in the ischemic/reperfused myocardium.