BACKGROUND Caloric restriction (CR) has been described to have cardioprotective effects and improve functional outcomes in animal models and humans. Chronic ischemic heart failure (HF) is associated with reduced cardiac sympathetic innervation, dysfunctional β-adrenergic receptor signaling, and decreased cardiac inotropic reserve. We tested the effects of a long-term CR diet, started late after myocardial infarction on cardiac function, sympathetic innervation, and β-adrenergic receptor responsiveness in a rat model of postischemic HF. METHODS AND RESULTS Adult male rats were randomly assigned to myocardial infarction or sham operation and 4 weeks later were further randomized to a 1-year CR or normal diet. One year of CR resulted in a significant reduction in body weight, heart weight, and heart weight/tibia length ratio when compared with normal diet in HF groups. At the end of the study period, echocardiography and histology revealed that HF animals under the CR diet had ameliorated left ventricular remodeling compared with HF rats fed with normal diet. Invasive hemodynamic showed a significant improvement of cardiac inotropic reserve in CR HF rats compared with HF-normal diet animals. Importantly, CR dietary regimen was associated with a significant increase of cardiac sympathetic innervation and with normalized cardiac β-adrenergic receptor levels in HF rats when compared with HF rats on the standard diet. CONCLUSIONS We demonstrate, for the first time, that chronic CR, when started after HF established, can ameliorate cardiac dysfunction and improve inotropic reserve. At the molecular level, we find that chronic CR diet significantly improves sympathetic cardiac innervation and β-adrenergic receptor levels in failing myocardium.

中文翻译：

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长期热量限制可改善缺血性心力衰竭模型中的心脏功能，重塑，肾上腺素能反应性和交感神经。

背景技术已经描述了热量限制（CR）在动物模型和人类中具有心脏保护作用并改善了功能结果。慢性缺血性心力衰竭（HF）与减少的心脏交感神经，功能障碍的β-肾上腺素能受体信号传导和减少的心脏正性肌力储备有关。我们测试了在心肌梗塞后晚期开始的长期CR饮食对缺血性HF大鼠模型中心功能，交感神经和β-肾上腺素能受体反应的影响。方法和结果成年雄性大鼠随机分为心肌梗塞或假手术，4周后进一步随机分为1年CR或正常饮食。一年的CR可显着降低体重，心脏重量，与正常饮食相比，HF组的心脏重量/胫骨长度比。在研究期结束时，超声心动图和组织学检查显示，与常规饮食喂养的HF大鼠相比，接受CR饮食的HF动物的左心室重构得到改善。与HF正常饮食动物相比，CR HF大鼠的侵入性血流动力学显示其心脏正性肌力储备有显着改善。重要的是，与标准饮食中的HF大鼠相比，CR饮食方案与HF大鼠心脏交感神经支配的显着增加以及与心脏β-肾上腺素能受体水平的正常化有关。结论我们首次证明了慢性心律失常在心力衰竭建立后开始可改善心脏功能障碍并改善正性肌力储备。在分子水平上