Wallenberg Laboratory at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Int J Cardiol. 2013 Oct 3;168(3):1943-50. doi: 10.1016/j.ijcard.2012.12.092. Epub 2013 Jan 26.
Stress-induced cardiomyopathy (SIC), also known as Takotsubo cardiomyopathy, is an acute cardiac syndrome with substantial morbidity and mortality. The unique hallmark of SIC is extensive ventricular akinesia involving apical segments with preserved function in basal segments. Adrenergic overstimulation plays an important role in initiating SIC but the pathophysiological pathways and receptors involved are unknown.
Sprague Dawley rats (~300 g) were injected with a single dose of the β-adrenergic agonist isoprenaline (ISO, i.p.) and echocardiography was used to study cardiac function. The akinetic part of the left ventricle was biopsied in six SIC patients. Amount of intracellular lipid and glycogen as well as degree of permanent cardiac damage were assessed by histology.
In rats, ISO at doses ≥ 50 mg/kg induced severe SIC-like regional akinesia that completely resolved within seven days. Intracellular lipid content was higher in akinetic, but not in normokinetic myocardium in both SIC patients and rats. β2-receptor blockade or Gi-pathway inhibition was associated with less widespread akinesia and low lipid accumulation but significantly increased acute mortality.
We provide a novel rat model of SIC that supports the hypothesis of circulating catecholamines as initiators of SIC. We propose that the β-adrenoreceptor pathway is important in the setting of severe catecholamine overstimulation and that perturbations of cardiac metabolism occur in SIC.
应激性心肌病（SIC），也称为心尖球囊样综合征，是一种具有较高发病率和死亡率的急性心脏综合征。SIC 的独特特征是广泛的心室运动障碍，涉及心尖段，基底段的功能保持正常。肾上腺素能过度刺激在引发 SIC 中起重要作用，但涉及的病理生理途径和受体尚不清楚。
向 Sprague Dawley 大鼠（~300g）单次注射β-肾上腺素能激动剂异丙肾上腺素（ISO，腹腔内注射），并使用超声心动图研究心功能。在六名 SIC 患者中，取左心室的无运动部分进行活检。通过组织学评估细胞内脂质和糖原的含量以及永久性心脏损伤的程度。
在大鼠中，剂量≥50mg/kg 的 ISO 诱导出严重的 SIC 样区域性运动障碍，在七天内完全缓解。在 SIC 患者和大鼠中，无运动但非正常运动的心肌中的细胞内脂质含量更高。β2-受体阻断或 Gi 通路抑制与广泛的运动障碍减轻和脂质蓄积减少相关，但显著增加了急性死亡率。
我们提供了一种新的 SIC 大鼠模型，支持了循环儿茶酚胺作为 SIC 引发剂的假说。我们提出，β-肾上腺素能受体途径在严重儿茶酚胺过度刺激的情况下很重要，并且 SIC 中存在心脏代谢紊乱。
