Stress-induced cardiomyopathy (SIC) results from a profound catecholaminergic surge during strong emotional or physical stress. SIC is characterized by acute left ventricular apex hypokinesia, in the absence of coronary arteries occlusion, and can lead to arrhythmias and acute heart failure. Although, most SIC patients recover, the process could be slow, and recurrence or death may occur. Despite that the SIC common denominator is a large catecholamine discharge, the pathophysiological mechanism is incompletely understood. It is thought that catecholamines have direct cytotoxicity on apical ventricular myocytes (VM), which have the highest β-adrenergic receptors density, and whose overstimulation might cause acute Ca2+ overload and oxidative stress, causing death in some VM and stunning others. Rodents receiving acute isoproterenol (ISO) overdose (OV) mimic SIC development, however, they have not been used to simultaneously assess Ca2+ handling and contractility status in isolated VM, which might explain ventricular hypokinesia. Therefore, treating rats with a single ISO-OV (67 mg/kg body weight), we sought out to characterize, with confocal imaging, Ca2+ and shortening dynamics in Fluo-4-loaded VM, during the early (1-5 days) and late post-acute phases (15 days). We found that ISO-OV VM showed contractile dysfunction; blunted shortening with slower force development and relaxation. These correlated with Ca2+ mishandling; blunted Ca2+ transient, with slower time to peak and SR Ca2+ recovery. SR Ca2+ content was low, nevertheless, diastolic Ca2+ sparks were more frequent, and their duration increased. Contractility and Ca2+ dysfunction aggravated or remained altered over time, explaining slow recovery. We conclude that diminished VM contractility is the main determinant of ISO-OV hypokinesia and is mostly related to Ca2+ mishandling.

中文翻译：

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同时评估急性异丙肾上腺素诱发的心肌病大鼠模型中离体心室肌细胞中钙处理和收缩动态的同时评估。

压力诱发的心肌病（SIC）是由强烈的情绪或身体压力引起的儿茶酚胺能激增引起的。SIC的特征是在没有冠状动脉闭塞的情况下出现急性左心室顶点运动减退，并可能导致心律不齐和急性心力衰竭。尽管大多数SIC患者可以康复，但过程可能很慢，并且可能复发或死亡。尽管SIC的共同点是大量的儿茶酚胺放电，但其病理生理机制尚不完全清楚。儿茶酚胺被认为对心室心肌细胞（VM）具有直接的细胞毒性，其最高的β-肾上腺素能受体密度，其过度刺激可能导致急性的Ca2 +超负荷和氧化应激，从而导致某些VM死亡并导致其他人昏迷。接受急性异丙肾上腺素（ISO）过量（OV）的啮齿动物模仿SIC的发展，但尚未用于同时评估孤立VM中Ca2 +的处理和收缩状态，这可能解释了心室运动不足。因此，我们用单一的ISO-OV（67 mg / kg体重）治疗大鼠，我们试图通过共聚焦成像来表征在早期（1-5天）的Fluo-4加载的VM中的Ca2 +和缩短的动力学过程。和急性后后期（15天）。我们发现ISO-OV VM表现出收缩功能障碍。钝化的缩短，力的产生和松弛变慢。这些与Ca2 +的错误处理有关。Ca2 +瞬变变钝，达到峰化和SR Ca2 +恢复的时间变慢。SR Ca2 +含量较低，但舒张期Ca2 +火花更为频繁，持续时间增加。收缩力和Ca2 +功能障碍随着时间的推移而加重或保持改变，说明恢复缓慢。我们得出的结论是，VM收缩力下降是ISO-OV运动减退的主要决定因素，并且主要与Ca2 +处理不当有关。