Flower R W, Blake D A
Pediatr Res. 1981 Sep;15(9):1293-1302. doi: 10.1203/00006450-198109000-00013.
Aspirin administration, at a dosage producing plasma levels within the human therapeutic range, caused marked inhibition of production of both vascular prostacyclin (a vasodilator) and platelet thromboxane (a vasoconstrictor) in beagle puppies. In addition, aspirin-treated, oxygen-exposed puppies developed retinopathy of significantly greater severity than their unmedicated, oxygen-exposed littermates. Direct ophthalmoscopic observations indicated that whereas sustained oxygen breathing produced retinal vasoconstriction in unmedicated puppies, retinal vessels of aspirin-treated littermates became more dilated or remained unchanged. It is postulated that retinal vasoconstriction may be a normal physiologic mechanism to protect the immature retina from damaging effects of high blood oxygen levels; i.e., it may be a protective rather than a pathologic process in response to hyperoxia. Many vascular anomalies which characterize the human disease were present in the retinas of the puppies. Several of the most severely affected puppies treated with aspirin even displayed grade III cicatricial retinopathy (falciform retinal fold). Thus, a major criticism of the retrolental fibroplasia animal model has been addressed by producing cicatricial retrolental fibroplasia in puppies, and the confidence with which results from experimental animal studies might be extrapolated to the clinical situation is thereby strengthened.
给小猎犬幼犬服用能使血浆水平处于人体治疗范围内的剂量的阿司匹林，会显著抑制血管前列环素（一种血管扩张剂）和血小板血栓素（一种血管收缩剂）的生成。此外，经阿司匹林治疗且暴露于氧气环境中的幼犬所患视网膜病变的严重程度明显高于未用药且暴露于氧气环境中的同窝幼犬。直接检眼镜观察表明，持续吸氧会使未用药幼犬的视网膜血管收缩，而经阿司匹林治疗的同窝幼犬的视网膜血管则变得更加扩张或保持不变。据推测，视网膜血管收缩可能是一种正常的生理机制，以保护未成熟的视网膜免受高血氧水平的损害；也就是说，它可能是对高氧的一种保护而非病理过程。幼犬的视网膜中存在许多人类疾病所特有的血管异常。几只受影响最严重的经阿司匹林治疗的幼犬甚至出现了III级瘢痕性视网膜病变（镰状视网膜皱襞）。因此，通过在幼犬中产生瘢痕性晶状体后纤维增生，解决了对晶状体后纤维增生动物模型的一个主要批评，从而增强了将实验动物研究结果外推至临床情况的可信度。
