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  • Title: Effect of a cardioselective alpha-tocopherol analogue on reperfusion injury in rats induced by myocardial ischaemia.
    Author: Petty MA, Dow J, Grisar JM, De Jong W.
    Journal: Eur J Pharmacol; 1991 Jan 17; 192(3):383-8. PubMed ID: 2055237.
    Abstract:
    Free radicals may cause some of the irreversible injury which occurs during myocardial ischaemia and reperfusion. In the present study the effects of a cardioselective, free radical scavenger, MDL 74270, which is an analogue of alpha-tocopherol, on myocardial infarct size in an anaesthetised rat model of coronary artery ligation (60 min) and reperfusion (30 min) has been evaluated. Infusion of MDL 74270 (0.3-3.0 mg/kg per h) commencing 10 min before occlusion until the end of reperfusion significantly reduced infarct size. The highest dose also caused a significant reduction in serum creatine phosphokinase levels. Similar findings have been obtained with the bromide salt of MDL 74270. Tissue distribution studies with 14C-labelled MDL 74270 and its tertiary amine analogue (MDL 74366) showed heart/blood ratios of total radioactivity, 1-6 h after i.v. administration, greater than 20 after MDL 74270 and around 1 after MDL 74366. The importance of accumulation of total radioactivity in the heart after MDL 74270 is supported by the fact that MDL 74366 was 30 times less potent as a myocardial protector in the ligation/reperfusion studies. It is concluded that MDL 74270 has potential for cardioprotective use in conditions of acute reperfusion.
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