IRFI-016, a new radical scavenger, limits ischemic damage following coronary artery occlusion in rats.
The effects of IRFI-016 [2(2,3 Dihydro-5-Acetoxy 4,6,7-Trimethyl-Benzofuranyl) acetic acid] a new radical scavenger were studied following six hours of myocardial ischemia, induced by left coronary artery occlusion in male rats. The loss of myocardial Creatinine Phosphokinase activity (CPK), myocardial Myeloperoxidase Activity (MPO), ECG, survival rate, and Pressure Rate Index (PRI) were evaluated in SHAM, control (vehicle i.p. injection) and IRFI-016 (200 mg/kg i.p., 30 minutes before occlusion) treated animals. CPK was significantly reduced and MPO significantly enhanced in the ischemic areas of the hearts obtained from vehicle treated rats when compared to SHAM operated ones. Pretreatment with IRFI-016 significantly attenuated (52%) loss of CPK activity in ischemic hearts and the increase in MPO activity, but did not increase PRI, thus indicating that this substance reduces the myocardial ischemic demand for oxygen. Occlusion of the coronary artery, furthermore, was associated with an immediate rise in the ST segment of the ECG, which was significantly attenuated by IRFI-016. These findings further support the important role of free radicals in the pathogenesis of acute myocardial ischemia and suggest that IRFI-016 may be a useful agent in the treatment of myocardial occlusion injury.
Campo
G M
GM
Institute of Pharmacology, School of Medicine, University of Messine, Italy.
Squadrito
F
F
Ioculano
M
M
Avenoso
A
A
Zingarelli
B
B
Calandra
S
S
Scuri
R
R
Saitta
A
A
Caputi
A P
AP
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001157:Arterial Occlusive Diseases / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D001572:Benzofurans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D004562:Electrocardiography; D016166:Free Radical Scavengers; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000031:analogs & derivatives*
D000975:Antioxidants; D001572:Benzofurans; D016166:Free Radical Scavengers; D014810:Vitamin E; C071049:Raxofelast