Carl-Ludwig-Institute of Physiology, University of Leipzig, 04103 Leipzig, Germany.
Department of Pediatric Cardiology, Heart Centre, University of Leipzig, 04289 Leipzig, Germany.
Int J Mol Sci. 2023 Jul 13;24(14):11417. doi: 10.3390/ijms241411417.
In rats, acute normobaric hypoxia depressed left ventricular (LV) inotropic function. After 24 h of hypoxic exposure, a slight recovery of LV function occurred. We speculated that prolonged hypoxia (72 h) would induce acclimatization and, hence, recovery of LV function. Moreover, we investigated biomarkers of nitrosative stress and apoptosis as possible causes of hypoxic LV depression. To elucidate the role of hypoxic sympathetic activation, we studied whether adrenergic blockade would further deteriorate the general state of the animals and their cardiac function. Ninety-four rats were exposed over 72 h either to normal room air (N) or to normobaric hypoxia (H). The rodents received infusion (0.1 mL/h) with 0.9% NaCl or with different adrenergic blockers. Despite clear signs of acclimatization to hypoxia, the LV depression continued persistently after 72 h of hypoxia. Immunohistochemical analyses revealed significant increases in markers of nitrosative stress, adenosine triphosphate deficiency and apoptosis in the myocardium, which could provide a possible explanation for the absence of LV function recovery. Adrenergic blockade had a slightly deteriorative effect on the hypoxic LV function compared to the hypoxic group with maintained sympathetic efficacy. These findings show that hypoxic sympathetic activation compensates, at least partially, for the compromised function in hypoxic conditions, therefore emphasizing its importance for hypoxia adaptation.
在大鼠中,急性常压低氧会抑制左心室(LV)的变力功能。在缺氧暴露 24 小时后,LV 功能会出现轻微恢复。我们推测,长时间缺氧(72 小时)会引起适应,从而恢复 LV 功能。此外,我们研究了硝化应激和细胞凋亡的生物标志物,以探讨其是否为 LV 抑制的可能原因。为了阐明缺氧性交感神经激活的作用,我们研究了肾上腺素能阻断是否会进一步恶化动物的一般状态及其心脏功能。94 只大鼠在 72 小时内分别暴露于正常室内空气(N)或常压低氧(H)中。这些啮齿动物接受 0.9%生理盐水(0.1 mL/h)或不同肾上腺素能阻滞剂的输注。尽管有明显的缺氧适应迹象,但在 72 小时的缺氧后,LV 抑制仍持续存在。免疫组织化学分析显示,心肌中硝化应激、三磷酸腺苷缺乏和细胞凋亡的标志物显著增加,这可能为 LV 功能恢复缺失提供了一种可能的解释。与保持交感神经效能的缺氧组相比,肾上腺素能阻断对缺氧性 LV 功能的影响略为恶化。这些发现表明,缺氧性交感神经激活至少部分代偿了缺氧条件下受损的功能,因此强调了其对缺氧适应的重要性。