REDUCTION OF MYOCARDIAL INFARCT SIZE IN RAT BY IRFI-048, A SELECTIVE ANALOG OF VITAMIN-E

The effects of IRFI-048 3-dihydro-5-methoxy-4,6,7-trimethyl-2-benzofur anyl acetic acid), a selective analogue of Vitamin E, on myocardial ti ssue injury were examined in anaesthetized rats subjected to 60-min oc clusion of the left coronary artery followed by 60-min reperfusion. In farct size (Evan's blue and tetrazolium stain), serum creatinphosphoki nase (CPK), plasma malonaldehyde (MAL), cardiac myeloperoxidase (MPO) activity, and ST-segment of electrocardiogram (ECG) and survival rate were evaluated. Postischaemic reperfusion produced severe cardiac necr osis, caused neutrophil (PMNs) infiltration (evaluated by MPO activity ) in the jeopardized tissue, increased serum CPK and plasma MAL, raise d ST-segment of ECG, and decreased survival rate. IRFI-048, (200 and 4 00 mg/kg o.s.) given to the rats 6 h before occlusion, caused a reduct ion of necrotic area expressed as a percentage of either the area at r isk or the total left ventricle, decreased MPO activity both in the ar ea at risk (from 3.2 +/- 0.3 U x 10(-3)/g tissue to 1.1 +/- 0.4 U x 10 (-3)/g tissue; p < .005) and in the necrotic area (from 5.7 +/- 0.9 U x 10(-3)/g tissue to 1.8 +/- 0.5 U x 10(-3)/g tissue; p < .001), atten uated the rise of ST-segment of ECG (from 0.51 +/- 0.14 mV in the vehi cle group to 0.28 +/- 0.11 mV in the treated group; p < .005), reduced the increase of plasma MAL and serum CPK during reperfusion (from 42 +/- 5.3 nmol/ml to 15 +/- 3.1 nmol/ml and 139 +/- 13 IU/100 ml to 58 /- 7.5 IU/100 ml, respectively; p < .001). Finally, IRFI-048 enhanced survival rate evaluated at the end of experiment. The results indicate that IRIF-048 significantly reduces myocardial infarct size and empha size the beneficial action of analogues of vitamin E on the prevention of lipid peroxidation.