Yamada T, Matsumori A, Okada I, Tominaga M, Kawai C
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Jpn Circ J. 1992 Nov;56(11):1138-45. doi: 10.1253/jcj.56.1138.
The purpose of this study was to investigate the therapeutic effect of an alpha 1-blocker, bunazosin, using an experimental murine model of congestive heart failure induced by viral myocarditis. This model is characterized by a high incidence of severe myocarditis and subsequent congestive heart failure, and is suitable for the evaluation of the effect of drugs. To estimate myocardial damage objectively and quantitatively, we used antimyosin monoclonal antibody in addition to histopathological grading. Four-week-old BALB/c mice were inoculated with encephalomyocarditis virus. The mice were injected daily with bunazosin or saline as a placebo from the day of viral inoculation until day 7 (protocol-I) or day 14 (protocol-II), or from day 4 to day 14 (protocol-III). They were then injected with 1.5 microCi of indium-111 labeled antimyosin antibody and were killed 24 h later. The antimyosin cardiac uptake was counted and histopathological grading was performed. The heart-weight to body-weight ratio, left ventricular dimension, histopathological grades and antimyosin cardiac uptake were significantly lower in the bunazosin group than in the placebo group in protocol-II, but not in protocol-I or protocol-III. Bunazosin showed a protective effect against viral myocarditis only when it was started early after infection and continued until the stage of congestive heart failure.
本研究的目的是使用由病毒性心肌炎诱导的充血性心力衰竭实验小鼠模型，研究α1受体阻滞剂布那唑嗪的治疗效果。该模型的特点是严重心肌炎及随后的充血性心力衰竭发病率高，适用于评估药物疗效。为了客观、定量地评估心肌损伤，除了组织病理学分级外，我们还使用了抗肌球蛋白单克隆抗体。将4周龄的BALB/c小鼠接种脑心肌炎病毒。从接种病毒之日起至第7天（方案I）或第14天（方案II），或从第4天至第14天（方案III），每天给小鼠注射布那唑嗪或作为安慰剂的生理盐水。然后给它们注射1.5微居里的铟-111标记抗肌球蛋白抗体，并在24小时后处死。计算抗肌球蛋白在心脏的摄取量，并进行组织病理学分级。在方案II中，布那唑嗪组的心脏重量与体重比、左心室尺寸、组织病理学分级和抗肌球蛋白心脏摄取量均显著低于安慰剂组，但在方案I或方案III中并非如此。布那唑嗪仅在感染后早期开始使用并持续至充血性心力衰竭阶段时，才对病毒性心肌炎显示出保护作用。
