Breathing and Oxygen Carrying Capacity in Ts65Dn and Down Syndrome.
Breathing and Oxygen Carrying Capacity in Ts65Dn and Down Syndrome.
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DOI：
10.1093/function/zqad058
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
患有唐氏综合征（Ds）的个体患呼吸道感染、吸入性肺炎和呼吸暂停的风险增加。Ts 65 Dn小鼠是一种常用的Ds模型，但尚未对这些小鼠的清醒呼吸和呼吸肌功能进行正式研究。我们假设，与野生型（WT）相比，Ts 65 Dn的呼吸将受损，并将由神经和肌肉输入介导。基线每分钟通气量在3、6或12个月龄时无差异。然而，VT/Ti（呼吸神经驱动的标志物）在Ts 65 Dn中低于WT，中枢性呼吸暂停更普遍。对呼吸缺氧的反应没有差异，但对高碳酸血症的反应减弱，揭示了Ts 65 Dn的二氧化碳感知和/或运动输出的差异。室内空气中存在氧饱和度下降，表明通风可能不足以维持Ts 65 Dn的充分氧饱和度。我们没有观察到动脉PO 2或PCO 2的差异，但Ts 65 Dn有较低的血红蛋白和红细胞压积。对52，346例D和52，346例对照的回顾性病历审查证实了D患者贫血的相对风险升高。我们还进行了正常呼吸的体内肌电图和体外肌肉功能和膈肌的组织纤维分型，发现菌株之间没有差异。总体而言，Ts 65 Dn的有意识呼吸受损，由神经机制介导，并导致血红蛋白饱和度降低。与WT相比，Ts 65 Dn的携氧能力降低，我们证明了Ds患者患贫血的风险也增加。
Individuals with Down syndrome (Ds) are at increased risk of respiratory infection, aspiration pneumonia, and apnea. The Ts65Dn mouse is a commonly used model of Ds, but there have been no formal investigations of awake breathing and respiratory muscle function in these mice. We hypothesized that breathing would be impaired in Ts65Dn vs. wild-type (WT), and would be mediated by both neural and muscular inputs. Baseline minute ventilation was not different at 3, 6, or 12 mo of age. However, VT/Ti, a marker of the neural drive to breathe, was lower in Ts65Dn vs. WT and central apneas were more prevalent. The response to breathing hypoxia was not different, but the response to hypercapnia was attenuated, revealing a difference in carbon dioxide sensing, and/or motor output in Ts65Dn. Oxygen desaturations were present in room air, demonstrating that ventilation may not be sufficient to maintain adequate oxygen saturation in Ts65Dn. We observed no differences in arterial PO2 or PCO2, but Ts65Dn had lower hemoglobin and hematocrit. A retrospective medical record review of 52,346 Ds and 52,346 controls confirmed an elevated relative risk of anemia in Ds. We also performed eupneic in-vivo electromyography and in-vitro muscle function and histological fiber typing of the diaphragm, and found no difference between strains. Overall, conscious respiration is impaired in Ts65Dn, is mediated by neural mechanisms, and results in reduced hemoglobin saturation. Oxygen carrying capacity is reduced in Ts65Dn vs. WT, and we demonstrate that individuals with Ds are also at increased risk of anemia.
影响因子：
2.7
作者：
McClung JM;Deruisseau KC;Whidden MA;Van Remmen H;Richardson A;Song W;Vrabas IS;Powers SK
通讯作者：
Powers SK
影响因子：
2.1
作者：
Tenenbaum A;Malkiel S;Wexler ID;Levy-Khademi F;Revel-Vilk S;Stepensky P
通讯作者：
Stepensky P