[Antagonism of collagen-induced ECG changes in rats by a thromboxane synthetase inhibitor, CV-4151].

Abstract

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.

• Authors: H Matsumura, Z Terashita, K Nishikawa, Y Imai
• Journal: Nihon yakurigaku zasshi. Folia pharmacologica Japonica (Nihon Yakurigaku Zasshi) Vol. 87 Issue 4 Pg. 397-404 (Apr 1986) ISSN: 0015-5691 [Print] Japan
• PMID: 3755113 (Publication Type: Comparative Study, English Abstract, Journal Article)

Chemical References

• Anti-Arrhythmia Agents
• Fatty Acids, Monounsaturated
• Fatty Acids, Unsaturated
• Pyridines
• Thiophenes
• Thromboxane B2
• 6-Ketoprostaglandin F1 alpha
• Collagen
• isbogrel
• Ticlopidine

Topics

• 6-Ketoprostaglandin F1 alpha (blood)
• Animals
• Anti-Arrhythmia Agents
• Arrhythmias, Cardiac (prevention & control)
• Collagen (antagonists & inhibitors)
• Coronary Disease (chemically induced, drug therapy)
• Electrocardiography
• Fatty Acids, Monounsaturated
• Fatty Acids, Unsaturated (therapeutic use)
• Humans
• Pyridines (therapeutic use)
• Rats
• Rats, Inbred Strains
• Thiophenes (therapeutic use)
• Thromboxane B2 (blood)
• Ticlopidine