Intermittent hypoxic preconditioning (IHP) is a well-established cardioprotective intervention in models of ischemia/reperfusion injury. Nevertheless, the significance of IHP in different cardiac pathologies remains elusive. In order to investigate the role of IHP and its effects on calcium-dependent signalization in HF, we employed a model of cardiomyopathy induced by doxorubicin (Dox), a widely used drug from the class of cardiotoxic antineoplastics, which was i.p. injected to Wistar rats (4 applications of 4 mg/kg/week). IHP-treated group was exposed to IHP for 2 weeks prior to Dox administration. IHP ameliorated Dox-induced reduction in cardiac output. Western blot analysis revealed increased expression of sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA2a) while the expression of hypoxia inducible factor (HIF)-1-α, which is a crucial regulator of hypoxia-inducible genes, was not changed. Animals administered with Dox had further decreased expression of TRPV1 and TRPV4 (transient receptor potential, vanilloid subtype) ion channels along with suppressed Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) activation. In summary, IHP-mediated improvement in cardiac output in the model of Dox-induced cardiomyopathy is likely a result of increased SERCA2a expression which could implicate IHP as a potential protective intervention in Dox cardiomyopathy, however, further analysis of observed effects is still required.

间歇性低氧预处理（IHP）是缺血/再灌注损伤模型中一种成熟的心脏保护干预措施。然而，IHP 在不同心脏病理学中的意义仍然难以捉摸。为了研究 IHP 的作用及其对心力衰竭中钙依赖性信号传导的影响，我们采用了阿霉素 (Dox) 诱导的心肌病模型，阿霉素是一种广泛使用的心脏毒性抗肿瘤药物，将其腹膜内注射给Wistar大鼠（每周 4 次，每次 4 毫克/公斤）。IHP 治疗组在 Dox 给药前暴露于 IHP 2 周。IHP 改善了 Dox 引起的心输出量减少。蛋白质印迹分析显示肌浆/内质网 Ca ^{2+表达增加}-ATP酶（SERCA2a），而缺氧诱导因子（HIF）-1-α（缺氧诱导基因的关键调节因子）的表达没有改变。给予 Dox 的动物进一步降低了 TRPV1 和 TRPV4（瞬时受体电位，香草酸亚型）离子通道的表达，并抑制了 Ca ²⁺ /钙调蛋白依赖性蛋白激酶 II (CaMKII) 的激活。总之，在 Dox 诱导的心肌病模型中，IHP 介导的心输出量改善可能是 SERCA2a 表达增加的结果，这可能表明 IHP 作为 Dox 心肌病的潜在保护性干预措施，然而，仍需要对观察到的效果进行进一步分析。