Botha C J, van der Lugt J J, Erasmus G L, Kellerman T S, Schultz R A, Vleggaar R
Department of Pharmacology and Toxicology, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa.
Onderstepoort J Vet Res. 1997 Sep;64(3):189-94.
The specific neurotoxic principle of Tylecodon wallichii (Harv.) Toelken subsp. wallichii, the cause of krimpsiekte in small stock, was isolated and identified as the previously described cumulative bufadienolide, cotyledoside. Krimpsiekte was experimentally induced in two sheep by the repeated intravenous administration of cotyledoside at the rate of 0.01-0.015 mg/kg body mass. On day 9, both animals developed clinical signs typical of krimpsiekte, which is characterized by tremors, paresis and recumbency. Both sheep had difficulty in controlling their hindquarters when attempting to lie down. No significant electrocardiograph abnormalities were detected during the experiment which confirms that cotyledoside at low doses does not overtly affect the electrical activity of the heart. No gross lesions were observed in the sheep. The most significant microscopic lesions comprised mild brain oedema and pronounced vacuolation of the white matter of thalamic nuclei. These lesions might explain some of the motor function deficiencies clinically observed in this syndrome. The previously held contention that these neurotoxic cardiac glycosides are indeed the cause of krimpsiekte is, therefore, confirmed.
瓦氏奇峰锦（Tylecodon wallichii (Harv.) Toelken subsp. wallichii）是小型家畜krimpsiekte病的病因，其特定的神经毒性成分已被分离并鉴定为先前描述的累积性蟾蜍二烯内酯——子叶苷。通过以0.01 - 0.015毫克/千克体重的剂量反复静脉注射子叶苷，在两只绵羊身上实验性诱发了krimpsiekte病。在第9天，两只动物都出现了krimpsiekte病的典型临床症状，其特征为震颤、轻瘫和卧地不起。两只绵羊在试图躺下时，控制其后肢都有困难。实验期间未检测到明显的心电图异常，这证实了低剂量的子叶苷不会明显影响心脏的电活动。在绵羊身上未观察到明显的肉眼可见病变。最显著的微观病变包括轻度脑水肿和丘脑核白质明显空泡化。这些病变可能解释了该综合征临床观察到的一些运动功能缺陷。因此，先前认为这些神经毒性强心苷确实是krimpsiekte病病因的观点得到了证实。
