PROTECTIVE EFFECTS OF IRFI-016 A NEW ANTIOXIDANT AGENT, IN MYOCARDIALDAMAGE, FOLLOWING CORONARY-ARTERY OCCLUSION AND REPERFUSION IN THE RAT

The new free radical scavenger IRFI-016 [2(2,3-dihydro-5-acetoxy 4-6,7 -trimethyl-benzofuranyl) acetic acid] was assessed in a rat model of m yocardial injury induced by 1 h of left coronary artery occlusion foll owed by 30 min of reperfusion. Myocardial ischaemia plus-reperfusion ( MI/R) produced severe cardiac necrosis, neutrophil infiltration in the jeopardized tissue, increased serum creatine kinase (CK) and ST segme nt of the electrocardiogram (ECG), lowered the pressure rate index (PR I), increased serum levels of tumour necrosis factor (TNF-alpha) and c aused a decrease in the survival rate. Administration of IRFI-016 (100 and 200 mg/kg i.p.) 30 min before occlusion resulted in a significant protective effect in post-ischaemic reperfusion. Compared with untrea ted rats, IRFI-016, in particular the dose of 200 mg/kg, caused a redu ction of the area at risk (55 +/- 4% in the MI/R vehicle group and 24 +/- 2.5% in the MI/R treated group; p < 0.001) or as a percentage of t he total left ventricle (23 +/- 3/4% in the MI/R vehicle group 8 +/- 2 .1% in the MI/R treated group; p < 0.005), reduced the myeloperoxidase activity, an index of neutrophil infiltration in the necrotic area (f rom 4.8 +/- 0.8 to 1.6 +/- 0.4 U/g tissue; p < 0.005), reduced the ser um levels of TNF-alpha (from 216 +/- 13 to 45 +/- 7 U/ml; p < 0.001), blunted in the rise of the ST segment of the ECG (from 0.47 +/- 0.13 m V in the vehicle group to 0.3 +/- 0.18 mV in the treated group; p < 0. 001), reduced the loss of CK (from 220 +/- 15 to 88 +/- 13 IU/ml of bl ood; p < 0.001) and improved the depressed PRI (from 56 +/- 4% to 78 /- 3% mm Hg/beats/min; p < 0.005). Finally, IRFI-016 significantly enh anced the survival rate evaluated at the end of the experiment. The re sults strongly indicate that IRFI-016 is a promising drug for cardiac ischaemia and reperfusion.