Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET- Universidad Nacional de Córdoba, Córdoba, Argentina.
Facultad de Psicología, Universidad Nacional de Córdoba, Córdoba, Argentina; Instituto de Investigaciones Psicológicas, IIPsi-CONICET-Universidad Nacional de Córdoba, Córdoba, Argentina.
Exp Neurol. 2021 Oct;344:113796. doi: 10.1016/j.expneurol.2021.113796. Epub 2021 Jul 3.
Early ethanol exposure affects respiratory neuroplasticity; a risk factor associated with the Sudden Infant Death Syndrome. High and chronic ethanol doses exert long-lasting effects upon respiratory rates, apneic episodes and ventilatory processes triggered by hypoxia. The present study was performed in 3-9-day-old rat pups. Respiratory processes under normoxic and hypoxic conditions were analyzed in pups intoxicated with different ethanol doses which were pre-exposed or not to the drug. A second major goal was to examine if acute and/or chronic early ethanol exposure affects blood parameters related with hypercapnic or hypoxic states. In Experiment 1, at postnatal day 9, animals previously treated with ethanol (2.0 g/kg) or vehicle (0.0 g/kg) were tested sober or intoxicated with 0.75, 1.37 or 2.00 g/kg ethanol. The test involved sequential air conditions defined as initial normoxia, hypoxia and recovery normoxia. Motor activity was also evaluated. In Experiment 2, blood parameters indicative of possible hypoxic and hypercapnic states were assessed as a function of early chronic or acute experiences with the drug. The main results of Experiment 1 were as follows: i) ethanol's depressant effects upon respiratory rates increased as a function of sequential treatment with the drug (sensitization); ii) ethanol inhibited apneic episodes even when employing the lowest dose at test (0.75 g/kg); iii) the hyperventilatory response caused by hypoxia negatively correlated with the ethanol dose administered at test; iv) ventilatory long-term facilitation (LTF) during recovery normoxia was observed in pups pre-exposed to the drug and in pups that received the different ethanol doses at test; v) self-grooming increased in pups treated with either 1.37 or 2.00 g/kg ethanol. The main result of Experiment 2 indicated that acute as well as chronic ethanol exposure results in acidosis-hypercapnia. The results indicate that early and brief experiences with ethanol are sufficient to affect different respiratory plasticity processes as well as blood biomarkers indicative of acidosis-hypercapnia. An association between the LTF process and the acidosis-hypercapnic state caused by ethanol seems to exist. The mentioned experiences with the drug are sufficient to result in an anomalous programming of respiratory patterns and metabolic conditions.
早期乙醇暴露会影响呼吸神经可塑性；这是与婴儿猝死综合征相关的一个风险因素。高浓度和慢性乙醇剂量会对呼吸频率、呼吸暂停发作和缺氧触发的通气过程产生持久影响。本研究在 3-9 天大的大鼠幼仔中进行。在预暴露或未暴露于药物的情况下，用不同剂量乙醇处理的幼仔在常氧和缺氧条件下的呼吸过程进行了分析。第二个主要目标是检查急性和/或慢性早期乙醇暴露是否会影响与高碳酸血症或低氧血症状态相关的血液参数。在实验 1 中，在出生后第 9 天，先前用乙醇（2.0 g/kg）或载体（0.0 g/kg）处理的动物清醒或用 0.75、1.37 或 2.00 g/kg 乙醇再次处理。测试包括定义为初始常氧、缺氧和恢复常氧的连续空气条件。还评估了运动活动。在实验 2 中，根据药物的早期慢性或急性经历，评估了指示可能缺氧和高碳酸血症状态的血液参数。实验 1 的主要结果如下：i）随着药物序贯治疗（敏化），乙醇对呼吸频率的抑制作用增加；ii）即使在测试中使用最低剂量（0.75 g/kg），乙醇也抑制呼吸暂停发作；iii）缺氧引起的过度通气反应与测试中给予的乙醇剂量呈负相关；iv）在药物预暴露的幼仔和接受不同乙醇剂量测试的幼仔中，恢复常氧时出现通气长期易化（LTF）；v）用 1.37 或 2.00 g/kg 乙醇处理的幼仔自我梳理增加。实验 2 的主要结果表明，急性和慢性乙醇暴露会导致酸中毒-高碳酸血症。结果表明，早期和短暂的乙醇接触足以影响不同的呼吸可塑性过程以及指示酸中毒-高碳酸血症的血液生物标志物。乙醇引起的 LTF 过程与酸中毒-高碳酸血症状态之间似乎存在关联。这种药物接触足以导致呼吸模式和代谢条件的异常编程。
