CA++ BLOCKERS IN ISCHEMIC/THROMBOTIC SUDDEN DEATH

CA 阻滞剂治疗缺血性/血栓性猝死

• 批准号: 3448607
• 负责人: ADAM K MYERS
• 金额: $ 5.36万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-12-01 至 1987-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3448607
• 关键词: adenosine diphosphate; antiarrhythmic agent; arachidonate; calcium channel blockers; coronary occlusion /thrombosis; heart pharmacology; myocardial ischemia /hypoxia; nifedipine; pimozide; platelet activating factor; sudden cardiac death; thrombin; thromboxanes; verapamil

Nifedipine, a Ca++ channel blocking drug used in cardiology, has been found to protect in clinical doses against a severe experimental thrombotic challenge. Although the Ca++ blockers are recognized as vasodilatory, antispasmodic and antiarrhythmic, evidence is accumulating that the antithrombotic effect may contribute to their clinical efficacy. It is therefore proposed to test, in a systematic quantitative manner, to what extent this class of drugs is antithrombotic and will protect against thrombotic sudden death. This will be done in a well-characterized mouse sudden death model which is both inexpensive and quantitative. The range of challenge agents will be substantially expanded to provide a wide variety of classes, ranging from intravenous thrombin, arachidonic acid, collagen, ADP and thromboxane A2 agonist to platelet-activating factor (PAF-acether). Sudden death induced by PAF-acether is anaphylactic rather than thrombotic, since mouse platelets are insensitive to PAF-acether in terms of aggregation. The Ca++ blocking drugs to be evaluated are nifedipine, verapamil, diltiazem, perhexilene and nitrendipine. These Ca++ blocking drugs will also be compared to the calmodulin antagonists trifluoperazine, pimozide and penfluridol. An especial effort will be made to evaluate post-challenge as well as pretreatment efficacy. Histopathological analyses will be used to relate thrombosis to degree of protection. EKG will be used to evaluate the extent to which the antiarrhythmic effect contributes to the protective action. The long term objective is to lay a sound experimental basis for an important and significant new application for Ca++ related drugs.

硝苯地平是一种用于心脏病学的钙离子通道阻断药物

项目成果

Thromboxane in sudden death.

血栓素导致猝死。

• 发表时间: 1985
• 期刊: Advances in prostaglandin, thromboxane, and leukotriene research
• 作者: Myers,AK;Ramwell,PW
• 通讯作者: Ramwell,PW

Antagonism of PAF-induced death in mice.

拮抗 PAF 诱导的小鼠死亡。

• DOI: 10.1016/0090-6980(88)90135-9
• 发表时间: 1988
• 期刊: Prostaglandins
• 作者: Myers,AK;Nakanishi,T;Ramwell,P
• 通讯作者: Ramwell,P

Role of adrenal steroids in the recovery from platelet activating factor challenge.

肾上腺类固醇在血小板激活因子挑战恢复中的作用。

• 发表时间: 1987
• 期刊: Circulatory shock
• 作者: Myers,AK;Bader,TJ
• 通讯作者: Bader,TJ

Pharmacological manipulation of platelet-activating factor toxicity in rodents.

啮齿动物血小板活化因子毒性的药理学操作。

• 发表时间: 1987
• 期刊: Advances in prostaglandin, thromboxane, and leukotriene research
• 作者: Myers,A;Duarte,AP;Ramwell,P
• 通讯作者: Ramwell,P

Comparison of verapamil and nifedipine in thrombosis models.

维拉帕米和硝苯地平在血栓模型中的比较。

• DOI: 10.3181/00379727-183-42390
• 发表时间: 1986
• 期刊: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)
• 作者: Myers,AK;Forman,G;TorresDuarte,AP;Penhos,J;Ramwell,P
• 通讯作者: Ramwell,P