Beneficial effects of astringinin, a resveratrol analogue, on the ischemiaand reperfusion damage in rat heart

Oxidative stress plays an important role in the pathogenesis of myocardial ischemia and infarction. Antioxidants might then be beneficial in the preve ntion of these diseases. Astringinin (3,3 ' ,4 ' ,5-tetrahydroxystilbene), a resveratrol (3,4 ' ,5-trihydroxystilbene) analogue with considerably high er antioxidative activity and free radical scavenging capacity, was introdu ced to examine its cardioprotective effects in ischemia or ischemia-reperfu sion (I/R) rats. In the present study, the left main coronary artery was oc cluded by the following procedures: (i) 30 min occlusion, (ii) 5 min occlus ion followed by 30 min reperfusion, and (iii) 4 h occlusion. Animals were i nfused with and without astringinin before coronary artery occlusion. Morta lity, and the severity of ischemia- and I/R-induced arrhythmias were compar ed. Pretreatment of astringinin dramatically reduced the incidence and dura tion of ventricular tachycardia (VT) and ventricular fibrillation (VF) duri ng either ischemia or IIR period. Astringinin at 2.5 X 10(-5) and 2.5 X 10( -4) g/kg completely prevented the mortality of animals during ischemia or I /R. During the same period, astringinin pretreatment also increased nitric oxide (NO) and decreased lactate dehydrogenase (LDH) levels in the carotid blood. In animals subjected to 4 h coronary occlusion, the cardiac infarct size (expressed as a percentage of occluded zone) was reduced from 44.4 +/- 4.1% to 19.1 +/- 2.4% by astringinin (2.5 x 10(-4) g/kg), We conclude that , astringinin is a potent antiarrhythmic agent with cardioprotective activi ty in ischemic and ischemic-reperfused rat heart. The beneficial effects of astringinin in the ischemic and ischemic-reperfused hearts may be correlat ed with its antioxidant activity and upregulation of NO production. (C) 200 1 Elsevier Science Inc.