[Antagonism of collagen-induced ECG changes in rats by a thromboxane synthetase inhibitor, CV-4151].
Ten weeks old male Sprague-Dawley rats were used. One mg/kg of a calfskin type III collagen was injected into a tail vein under pentobarbital anesthesia, and the electrocardiogram (ECG) was recorded via leads I, II and III for 10 min. Abnormal ECG patterns, i.e., ST-T changes and incidence of arrhythmia, were shown after collagen injection, and some rats suffered cardiac arrest. Oral administration of (E)-7-phenyl-7-(3-pyridyl)-6-heptenoic acid (CV-4151), a thromboxane synthetase inhibitor, at the dose of 10 mg/kg two hr before the collagen injection made the ST-T changes small, and it reduced the incidence of cardiac arrest. The effect of CV-4151 was greater than that of 30 mg/kg of ticlopidine with the same type of treatment. Neither CV-4151 nor ticlopidine had any affect on collagen-induced decreases in the blood platelet count. However, plasma thromboxane (TX) B2 level in the CV-4151-treated group was very low in comparison with those in both the control and ticlopidine-treated groups at 10 min after the collagen injection. These findings indicate that TXA2 may contribute, at least partly, to the collagen-induced ECG changes and indicate that CV-4151 might be a favorable agent for the prevention of TXA2-mediated cardiac ischemia.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D003094:Collagen / Q000037:antagonists & inhibitors; D003327:Coronary Disease / Q000139:chemically induced / Q000188:drug therapy*; D004562:Electrocardiography; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated / Q000627:therapeutic use*; D006801:Humans; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013876:Thiophenes / Q000627:therapeutic use; D013929:Thromboxane B2 / Q000097:blood; D013988:Ticlopidine
D000889:Anti-Arrhythmia Agents; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D011725:Pyridines; D013876:Thiophenes; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003094:Collagen; C045446:isbogrel; D013988:Ticlopidine