title: Effect of a cardioselective alpha-tocopherol analogue on reperfusion injury in rats induced by myocardial ischaemia.
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.
authors.affiliation: Merrell Dow Research Institute, Strasbourg, France.
authors.forename: M A
authors.initials: MA
authors.lastname: Petty
authors.forename: J
authors.initials: J
authors.lastname: Dow
authors.forename: J M
authors.initials: JM
authors.lastname: Grisar
authors.forename: W
authors.initials: W
authors.lastname: De Jong
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000493:pharmacokinetics / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D003402:Creatine Kinase / Q000097:blood; D016166:Free Radical Scavengers; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D001578:Benzopyrans; D002250:Carbon Radioisotopes; D016166:Free Radical Scavengers; C064728:MDL 74270; C069478:MDL 74366; D014810:Vitamin E; D003402:Creatine Kinase