McDonald Fiona B, Chandrasekharan Kumaran, Wilson Richard J A, Hasan Shabih U
Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Faculty of Medicine, University of Calgary, Alberta, Canada; and.
Section of Neonatal-Perinatal Medicine, Department of Pediatrics, Faculty of Medicine, Health Sciences Centre, University of Calgary, Alberta, Canada.
Am J Physiol Regul Integr Comp Physiol. 2016 Dec 1;311(6):R1113-R1124. doi: 10.1152/ajpregu.00062.2016. Epub 2016 Oct 12.
Maternal cigarette smoke (CS) exposure exhibits a strong epidemiological association with Sudden Infant Death Syndrome, but other environmental stressors, including infection, hyperthermia, and hypoxia, have also been postulated as important risk factors. This study examines whether maternal CS exposure causes maladaptations within homeostatic control networks by influencing the response to lipopolysaccharide, heat stress, and/or hypoxia in neonatal rats. Pregnant dams were exposed to CS or parallel sham treatments daily for the length of gestation. Offspring were studied at postnatal days 6-8 at ambient temperatures (T) of 33°C or 38°C. Within each group, rats were allocated to control, saline, or LPS (200 µg/kg) treatments. Cardiorespiratory patterns were examined using head-out plethysmography and ECG surface electrodes during normoxia and hypoxia (10% O). Serum cytokine concentrations were quantified from samples taken at the end of each experiment. Our results suggest maternal CS exposure does not alter minute ventilation (V̇e) or heart rate (HR) response to infection or high temperature, but independently increases apnea frequency. CS also primes the inflammatory system to elicit a stronger cytokine response to bacterial insult. High T independently depresses V̇e but augments the hypoxia-induced increase in V̇e Moreover, higher T increases HR during normoxia and hypoxia, and in the presence of an immune challenge, increases HR during normoxia, and reduces the increase normally associated with hypoxia. Thus, while most environmental risk factors increase the burden on the cardiorespiratory system in early life, hyperthermia and infection blunt the normal HR response to hypoxia, and gestational CS independently destabilizes breathing by increasing apneas.
母亲暴露于香烟烟雾（CS）与婴儿猝死综合征存在很强的流行病学关联，但其他环境应激源，包括感染、高温和缺氧，也被认为是重要的风险因素。本研究探讨母亲暴露于CS是否会通过影响新生大鼠对脂多糖、热应激和/或缺氧的反应，导致体内稳态控制网络出现适应不良。在整个妊娠期，怀孕的母鼠每天接受CS暴露或平行的假处理。在出生后第6 - 8天，将后代置于33°C或38°C的环境温度（T）下进行研究。在每组中，将大鼠分配至对照、生理盐水或LPS（200 µg/kg）处理组。在常氧和缺氧（10% O）期间，使用头部外置体积描记法和心电图表面电极检查心肺模式。从每个实验结束时采集的样本中定量血清细胞因子浓度。我们的结果表明，母亲暴露于CS不会改变对感染或高温的分钟通气量（V̇e）或心率（HR）反应，但会独立增加呼吸暂停频率。CS还会使炎症系统致敏，以引发对细菌感染更强的细胞因子反应。高温独立降低V̇e，但增强缺氧诱导的V̇e增加。此外，较高温度在常氧和缺氧期间增加HR，并且在存在免疫挑战时，在常氧期间增加HR，并减少通常与缺氧相关的增加。因此，虽然大多数环境风险因素会增加生命早期心肺系统的负担，但高温和感染会减弱对缺氧的正常HR反应，而孕期CS暴露会通过增加呼吸暂停独立地破坏呼吸稳定性。
