关键词: Catecholamine Rat model Stress cardiomyopathy Takotsubo syndrome

来  源:   DOI:10.1093/ehjopen/oeae048   PDF(Pubmed)

Abstract:
UNASSIGNED: Adequate animal models are necessary to understand human conditions, such as takotsubo syndrome (TS) characterized by the heart\'s transient regional wall motion abnormalities. This study aims to develop a reproducible, low-mortality TS model that closely mimics the human condition and addresses the limitations of existing models.
UNASSIGNED: We conducted six experiments using 309 Sprague Dawley rats, each approximately 300 g and aged 7-8 weeks. Initially, we replicated an established model using intraperitoneal isoprenaline injections. Subsequent experiments varied the doses and infusion durations of intravenous isoprenaline and assessed the effects of sex, strain, and breeder on the development of reversible akinetic segments. High-resolution echocardiography monitored the regional wall motion over 30 days to correlate with histological changes. Increasing the isoprenaline dose and the infusion time significantly enhanced akinesia (P < 0.01), resulting in pronounced apical ballooning observed in three-dimensional imaging. Akinesia peaked at 6 h post-infusion, with recovery observed at 24 h; most rats recovered from akinetic segments within 48-72 h. Optimizing the mode of administration, dose, and duration achieved a TS-like phenotype in 90% of cases, with a 16.7% mortality rate. Histological examinations confirmed that myocardial injury occurred, independent of apical ballooning.
UNASSIGNED: This study presents a refined TS model that reliably replicates the syndrome\'s key features, including morphological and electrocardiographic changes, demonstrating its transient nature with high fidelity and reduced mortality. The model\'s reproducibility, evidenced by consistent results across trials, suggests its potential for broader application pending further validation.
摘要:
充分的动物模型对于了解人类状况是必要的,如Takotsubo综合征(TS),其特征是心脏短暂的局部室壁运动异常。这项研究旨在开发一种可重复的,低死亡率TS模型,紧密模仿人类状况,解决了现有模型的局限性。
我们用309只SpragueDawley大鼠进行了6次实验,每个约300克,年龄7-8周。最初,我们使用腹膜内注射异丙肾上腺素复制了已建立的模型.随后的实验改变了静脉注射异丙肾上腺素的剂量和输注持续时间,并评估了性别的影响。应变,和可逆运动节段发育的育种者。高分辨率超声心动图在30天内监测区域壁运动,以与组织学变化相关。增加异丙肾上腺素剂量和输注时间显着增强了运动障碍(P<0.01)。导致在三维成像中观察到明显的心尖膨胀。运动障碍在输注后6小时达到峰值,在24小时观察到恢复;大多数大鼠在48-72小时内从运动节段恢复。优化给药模式,剂量,持续时间在90%的病例中达到TS样表型,死亡率为16.7%。组织学检查证实心肌损伤发生,独立于顶端膨胀。
这项研究提出了一种完善的TS模型,可以可靠地复制综合症的关键特征,包括形态学和心电图改变,证明其短暂性,具有高保真度和降低死亡率。模型的可重复性,各试验结果一致证明,表明其具有更广泛的应用潜力,有待进一步验证。
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