Johnstone I B
Can J Comp Med. 1983 Apr;47(2):172-9.
Nonsteroidal anti-inflammatory drugs are commonly used in the treatment of inflammatory conditions, and have potential value in the treatment of thrombotic disease in the horse. This study compares the potency of three nonsteroidal anti-inflammatory drugs phenylbutazone, naproxen (equiproxen) and flunixin meglumine (banamine) with respect to their effects on equine platelets. Two functional responses of horse platelets were evaluated in vitro: their ability to aggregate and their ability to make available platelet factor 3 procoagulant activity. Flunixin at a concentration of 10(-6) M significantly depressed the maximum degree of adenosine diphosphate-induced (10(-6)M) aggregation while much higher concentrations of phenylbutazone and naproxen (5 X 10(5)M) were required to produce similar effects. None of the non-steriodal anti-inflammatory drugs significantly affected the duration of the lag phase or the initial velocity of adenosine diphosphate-induced aggregation within the range of drug concentrations used (10(-6)-10(-3)M). The lag phase and initial velocity of acid-soluble collagen-induced aggregation were significantly affected by 10(-6) M flunixin and 10(-4) M phenylbutazone or naproxen was required to produce equivalent effects. Concentrations of 5 X 10(-6) M flunixin and 5 X 10(-4) M phenylbutazone or naproxen were required to significantly depress the degree of collaen-induced aggregation of horse platelets. Although the effects of the nonsteroidal anti-inflammatory drugs were qualitatively similar, flunixin was a much more potent inhibitor of platelet aggregation than either of the other two drugs (which were equipotent). At very high drug concentrations (5 X 10(-4) M and greater), all three drugs produced the same degree of inhibition of equine platelet aggregation. Platelet factor 3 activity was made available by exposing horse platelets to 10(-5) M adenosine diphosphate or 1:800 acid-soluble collagen; but not by exposure to a suspension of kaolin particles. Only a small portion of the total platelet factor 3 activity was made available on stimulation with either adenosine diphosphate or collagen. Pretreatment of horse platelets with any of the nonsteroidal anti-inflammatory drugs (10(-4) M concentration) had no significant effect on adenosine diphosphate or collagen-induced platelet factor 3 availability.
非甾体抗炎药常用于治疗炎症性疾病，在马的血栓性疾病治疗中具有潜在价值。本研究比较了三种非甾体抗炎药——保泰松、萘普生（ Equiproxen ）和氟尼辛葡甲胺（ Banamine ）对马血小板的作用效力。体外评估了马血小板的两种功能反应：它们的聚集能力以及使血小板因子3促凝活性发挥作用的能力。浓度为10（-6）M的氟尼辛显著降低了二磷酸腺苷（10（-6）M）诱导的最大聚集程度，而保泰松和萘普生需要更高的浓度（5×10（-5）M）才能产生类似效果。在所使用的药物浓度范围（10（-6）-10（-3）M）内，没有一种非甾体抗炎药显著影响二磷酸腺苷诱导聚集的延迟期持续时间或初始速度。10（-6）M的氟尼辛显著影响了酸溶性胶原诱导聚集的延迟期和初始速度，而需要10（-4）M的保泰松或萘普生才能产生同等效果。需要5×10（-6）M的氟尼辛和5×10（-4）M的保泰松或萘普生才能显著降低马血小板胶原诱导的聚集程度。虽然非甾体抗炎药的作用在性质上相似，但氟尼辛作为血小板聚集抑制剂比其他两种药物（效力相当）的效力要强得多。在非常高的药物浓度（5×10（-4）M及更高）下，所有三种药物对马血小板聚集的抑制程度相同。通过将马血小板暴露于10（-5）M二磷酸腺苷或1:800酸溶性胶原可使血小板因子3活性发挥作用；但暴露于高岭土颗粒悬浮液则不能。在用二磷酸腺苷或胶原刺激时，只有一小部分总血小板因子3活性得以发挥作用。用任何一种非甾体抗炎药（浓度为10（-4）M）预处理马血小板对二磷酸腺苷或胶原诱导的血小板因子3活性发挥没有显著影响。
