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.