González-Candia Alejandro, Candia Alejandro A, Paz Adolfo, Mobarec Fuad, Urbina-Varela Rodrigo, Campo Andrea Del, Herrera Emilio A, Castillo Rodrigo L
Institute of Health Sciences, University of O'Higgins, Rancagua 2820000, Chile.
Laboratory of Vascular Function & Reactivity, Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago 7500922, Chile.
Antioxidants (Basel). 2022 May 25;11(6):1043. doi: 10.3390/antiox11061043.
More than 80 million people live and work (in a chronic or intermittent form) above 2500 masl, and 35 million live in the Andean Mountains. Furthermore, in Chile, it is estimated that 100,000 people work in high-altitude shifts, where stays in the lowlands are interspersed with working visits in the highlands. Acute exposure to high altitude has been shown to induce oxidative stress in healthy human lowlanders due to increased free radical formation and decreased antioxidant capacity. However, intermittent hypoxia (IH) induces preconditioning in animal models, generating cardioprotection. Here, we aim to describe the responses of a cardiac function to four cycles of intermittent hypobaric hypoxia (IHH) in a rat model. The twelve adult Wistar rats were randomly divided into two equal groups, a four-cycle of IHH and a normobaric hypoxic control. Intermittent hypoxia was induced in a hypobaric chamber in four continuous cycles (1 cycle = 4 days of hypoxia + 4 days of normoxia), reaching a barometric pressure equivalent to 4600 m of altitude (428 Torr). At the end of the fourth cycle, cardiac structural and functional variables were also determined by echocardiography; furthermore, cardiac oxidative stress biomarkers (4-Hydroxynonenal, HNE; nitrotyrosine, NT), antioxidant enzymes, and NLRP3 inflammasome panel expression are also determined. Our results show a higher ejection and a shortening fraction of the left ventricle function by the end of the fourth cycle. Furthermore, cardiac tissue presented a decreased expression of antioxidant proteins. However, a decrease in IL-1β, TNF-αn, and oxidative stress markers is observed in IHH compared to normobaric hypoxic controls. Non-significant differences were found in protein levels of NLRP3 and caspase-1. IHH exposure determines structural and functional heart changes. These findings suggest that initial states of IHH are beneficial for cardiovascular function and protection.
超过8000万人（长期或间歇性地）生活和工作在海拔2500米以上的地区，其中3500万人生活在安第斯山脉。此外，据估计，在智利有10万人从事高海拔轮班工作，他们在低地停留的时间穿插着在高地的工作访问。已有研究表明，健康的低地人急性暴露于高海拔环境会因自由基形成增加和抗氧化能力下降而导致氧化应激。然而，间歇性低氧（IH）在动物模型中可诱导预处理，产生心脏保护作用。在此，我们旨在描述大鼠模型中心脏功能对四个周期间歇性低压低氧（IHH）的反应。将12只成年Wistar大鼠随机分为两组，每组数量相等，一组接受四个周期的IHH，另一组为常压低氧对照组。在低压舱中诱导间歇性低氧，持续四个连续周期（1个周期 = 4天低氧 + 4天常氧），达到相当于海拔4600米（428托）的气压。在第四个周期结束时，还通过超声心动图测定心脏结构和功能变量；此外，还测定心脏氧化应激生物标志物（4-羟基壬烯醛，HNE；硝基酪氨酸，NT）、抗氧化酶以及NLRP3炎性小体相关蛋白的表达。我们的结果显示，在第四个周期结束时，左心室功能的射血分数和缩短分数更高。此外，心脏组织中抗氧化蛋白的表达降低。然而，与常压低氧对照组相比，IHH组中白细胞介素-1β、肿瘤坏死因子-α以及氧化应激标志物减少。NLRP3和半胱天冬酶-1的蛋白水平未发现显著差异。暴露于IHH会导致心脏结构和功能发生变化。这些发现表明，IHH的初始状态对心血管功能和保护有益。
