Ren Shuxun, Chang Sunny, Tran Alex, Mandelli Arianna, Wang Yibin, Wang Jessica J
Department of Anesthesiology, University of California.
Department of Medicine, University of California.
J Vis Exp. 2019 Oct 3(152). doi: 10.3791/59646.
Isoproterenol (ISO), is a non-selective beta-adrenergic agonist, that is used widely to induce cardiac injury in mice. While the acute model mimics stress-induced cardiomyopathy, the chronic model, administered through an osmotic pump, mimics advanced heart failure in humans. The purpose of the described protocol is to create the chronic ISO-induced heart failure model in mice using an implanted mini-pump. This protocol has been used to induce heart failure in 100+ strains of inbred mice. Techniques on surgical pump implantation are described in detail and may be relevant to anyone interested in creating a heart failure model in mice. In addition, the weekly cardiac remodeling changes based on echocardiographic parameters for each strain and expected time to model development are presented. In summary, the method is simple and reproducible. Continuous ISO administered via the implanted mini-pump over 3 to 4 weeks is sufficient to induce cardiac remodeling. Finally, the success for ISO model creation may be assessed in vivo by serial echocardiography demonstrating hypertrophy, ventricular dilation, and dysfunction.
异丙肾上腺素（ISO）是一种非选择性β-肾上腺素能激动剂，广泛用于诱导小鼠心脏损伤。急性模型模拟应激性心肌病，而通过渗透泵给药的慢性模型则模拟人类晚期心力衰竭。所述方案的目的是使用植入式微型泵在小鼠中创建慢性ISO诱导的心力衰竭模型。该方案已用于100多种近交系小鼠诱导心力衰竭。详细描述了手术泵植入技术，这可能与任何有兴趣在小鼠中创建心力衰竭模型的人相关。此外，还介绍了基于超声心动图参数的每个品系每周心脏重塑变化以及模型发育的预期时间。总之，该方法简单且可重复。通过植入式微型泵连续3至4周给予ISO足以诱导心脏重塑。最后，ISO模型创建的成功与否可通过连续超声心动图在体内评估，显示心肌肥厚、心室扩张和功能障碍。
