Honour A J, Hockaday T D, Mann J I
Br J Exp Pathol. 1977 Jun;58(3):268-72.
In rabbits previously injected i.v. with alloxan, serial observations of platelet thrombus formation in response to topical adenosine diphosphate (ADP) at sites of electrical injuries in pial arteries have been made. Using this model we have studied the effects of oral daily doses of dipyridamole (Persantin) and acetyl salicylic acid (ASA) upon platelet thrombus formation. Oral daily doses of 42 mg of ASA and 6 mg dipyridamole given separately in alloxan-treated rabbits are without effect. When given together orally, 42 mg and 6 mg respectively reduced the level of sensitivity to ADP for producing platelet thrombi to that established for the rabbits before the injection of alloxan. But withdrawal of these combined doses of dipyridamole and ASA caused the sensitivity of ADP for platelet thrombus formation to be raised to the much increased level present in rabbits soon after they are given i.v. alloxan. This apparent synergistic behaviour displayed by dipyridamole and ASA in these rabbits results in antithrombotic effects which are clearly absent when these two agents are given separately. It is of interest that the dose levels used here are equivalent, an a body weight ratio, to those being used in man in the current Persantin-Aspirin Reinfarction Study.
在预先经静脉注射四氧嘧啶的家兔中,对软脑膜动脉电损伤部位局部应用二磷酸腺苷(ADP)后血小板血栓形成进行了系列观察。利用该模型,我们研究了每日口服双嘧达莫(潘生丁)和乙酰水杨酸(ASA)对血小板血栓形成的影响。在经四氧嘧啶处理的家兔中,分别每日口服42mg ASA和6mg双嘧达莫没有效果。当一起口服时,42mg ASA和6mg双嘧达莫分别将产生血小板血栓的ADP敏感性水平降低至注射四氧嘧啶前家兔所确定的水平。但是停用双嘧达莫和ASA的这些联合剂量后,ADP对血小板血栓形成的敏感性升高至家兔静脉注射四氧嘧啶后不久出现的显著升高水平。双嘧达莫和ASA在这些家兔中表现出的这种明显协同行为导致了抗血栓作用,而这两种药物单独使用时显然没有这种作用。有趣的是,这里使用的剂量水平按体重比与当前潘生丁 - 阿司匹林再梗死研究中人类使用的剂量相当。