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Isoproterenol-induced myocardial injury and diastolic dysfunction in mice: structural and functional correlates

机译:异丙肾上腺素诱发的小鼠心肌损伤和舒张功能障碍:结构和功能相关

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The objective of this study was to determine whether a simple, noninvasive method involving administration of isoproterenol could be used to produce myocardial injury and cardiac dysfunction in the mouse heart with a low incidence of mortality. Adult Swiss-Webster mice were injected with isoproterenol (100 mg/kg SC) once daily for 5 d. Myocardial histology and left ventricular (LV) function were assessed 10 to 14 d after the last isoproterenol injection in 14 surviving isoproterenol-treated mice and 15 saline-treated control mice. Left ventricular systolic and diastolic pressures were evaluated in vitro by means of isovolumically contracting, perfused Langendorff preparations. Isoproterenol induced marked endocardial injury, associated with hypertrophy of surviving myocytes, and an increase in myocardial fibrosis (collagen types I and III according to picrosirius red microscopy). The hearts from isoproterenol-treated mice demonstrated decreased LV compliance, as evidenced by an upward shift in the diastolic pressure-volume relationship, with normal LV systolic function. Isoproterenol administration provides a simple, noninvasive means to induce endocardial injury and diastolic dysfunction without significant impairment of systolic function. This model has a low incidence of mortality and may be useful to assess the effects of gene or stem cell therapy on cardiac dysfunction without the potential confounding effects of invasive procedures.
机译:这项研究的目的是确定是否可以使用一种简单的,无创的,涉及异丙肾上腺素的方法,在死亡率较低的小鼠心脏中引起心肌损伤和心脏功能障碍。每天一次向成年的Swiss-Webster小鼠注射异丙肾上腺素(100 mg / kg SC),持续5天。在最后的异丙肾上腺素注射后,在14只存活的异丙肾上腺素治疗的小鼠和15只盐水治疗的对照小鼠中,在最后一次注射异丙肾上腺素后10至14天,评估了心肌组织学和左心室(LV)功能。通过等容收缩,灌注的Langendorff制剂在体外评估左心室收缩压和舒张压。异丙肾上腺素可引起明显的心内膜损伤,与存活的心肌细胞肥大有关,并且心肌纤维化增加(根据picrosirius红色显微镜检查,胶原蛋白类型为I和III)。接受异丙肾上腺素治疗的小鼠的心脏表现出左室顺应性降低,这是由舒张压-容积关系的上移所证实的,具有正常的左室收缩功能。异丙肾上腺素的给药提供了一种简单的,无创的方法,可诱发心内膜损伤和舒张功能障碍,而不会明显损害收缩功能。该模型死亡率低,可用于评估基因或干细胞疗法对心脏功能障碍的影响,而不会引起侵入性手术的潜在混淆。

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