Cinobufotalin injection, a traditional Chinese medicine preparation, successfully used for several years, might induce cardiotoxicity. The aim of the study was to evaluate the cardiotoxicity of cinobufotalin injection and the cardiotoxicity-preventive effect of sodium phenytoin in vivo. According to the 4 × 4 Latin square design, four Beagle dogs were allocated into four dose levels of 0, 0.3, 1, and 3 g/kg in treatment phases I–IV (cinobufotalin injection) and 3 g/kg in treatment phase V (cardiotoxicity antidote). The following parameters and endpoints were assessed: clinical observations, body weight, indicators of myocardial injury, and electrocardiogram (ECG) parameters. The cinobufotalin injection-related changes were observed in clinical observations (rapid breathing pattern), indicators of myocardial injury (increased cardiac troponin I, creatine kinase isoenzymes, and aspartate aminotransferase), and ECG graphics (arrhythmia) at 3 g/kg concentration in treatment phases I–IV. The cardiotoxicity of cinobufotalin injection was attenuated by sodium phenytoin in treatment phase V. The results confirmed the cardiotoxicity of cinobufotalin injection, and they might bring information about the appropriate monitoring time points and cardiotoxicity parameters in clinical practices and shed light on the treatment of cardiovascular adverse reactions.

中文翻译：

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cinobufotalin注射液的安全性重新评估：心脏毒性的新发现。

西诺布他林注射液是一种成功的中药制剂，已成功使用数年，可能会诱发心脏毒性。这项研究的目的是评估cinofufotalin注射液的心脏毒性和苯妥英钠的体内心脏预防作用。根据4×4拉丁方形设计，在治疗阶段I–IV（cinobufotalin注射）中将四只比格犬分为0、0.3、1和3 g / kg的四种剂量水平，在治疗阶段V中将其分为3 g / kg的四种剂量（心脏毒性解毒剂）。评估以下参数和终点：临床观察，体重，心肌损伤指标和心电图（ECG）参数。在临床观察（快速呼吸模式），心肌损伤指标（心肌肌钙蛋白I增加，肌酸激酶同工酶和天冬氨酸转氨酶）和心电图（心律失常）浓度为3 g / kg的情况下观察到了与cinobufotalin注射相关的变化。第一至第四阶段。在治疗阶段V中苯妥英钠可减轻cinobufotalin注射液的心脏毒性。