Effects of pretreatment with 2-O-octadecylascorbic acid, a novel free radical scavenger, on reperfusion-induced arrhythmias in isolated perfused rat hearts.
The effects of pretreatment with 2-O-octadecylascorbic acid (CV-3611), a novel liposoluble free radical scavenger, on reperfusion-induced arrhythmias were studied in isolated perfused rat hearts (n = 15 per group). The hearts were subjected to 10 min of coronary artery occlusion and 3 min of reperfusion. Pretreatment with CV-3611 (5 and 20 mg/kg) reduced the incidence of ventricular fibrillation (VF; reversible plus sustained) from its control value of 93% to 47% (p less than 0.05). Furthermore, CV-3611 reduced the incidence of sustained VF in a dose-dependent manner, from 67% in the control group to 13% in the CV-3611, 20 mg/kg treated group (p less than 0.01). CV-3611 (5 and 20 mg/kg) reduced the incidence of ventricular tachycardia (VT) from its control value of 93% to 73%. Pretreatment with ascorbic acid (5 mg/kg) had no effect on VF and VT. The myocardial content of CV-3611 was proportional to the dosage. We concluded that CV-3611 could reduce significantly the susceptibility to reperfusion-induced arrhythmias, especially VF, and that its effect may be due to the elimination of oxygen-derived free radicals by CV-3611 present in the membrane and the capture of lipid radicals, thereby inhibiting lipid peroxidation.
Tada
H
H
Third Department of Internal Medicine, Fukui Medical School, Japan.
Kutsumi
Y
Y
Misawa
T
T
Shimamoto
N
N
Nakai
T
T
Miyabo
S
S
D000818:Animals; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000503:physiopathology / Q000517:prevention & control*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology; D003331:Coronary Vessels / Q000502:physiology; D004562:Electrocardiography; D016166:Free Radical Scavengers; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D000889:Anti-Arrhythmia Agents; D016166:Free Radical Scavengers; C061185:2-O-octadecylascorbic acid; D001205:Ascorbic Acid