Melton J E, Neubauer J A, Edelman N H
Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick 08903-0019.
J Appl Physiol (1985). 1990 Oct;69(4):1296-301. doi: 10.1152/jappl.1990.69.4.1296.
We assessed the role of gamma-aminobutyric acid (GABA) as a potential causative agent of hypoxic respiratory depression by monitoring the response of the phrenic neurogram to systemic infusion of the GABA antagonist bicuculline (0.01 mg.kg-1.min-1) under control conditions and during isocapnic brain hypoxia produced by CO inhalation in separate groups of anesthetized, glomectomized, vagotomized, paralyzed, and ventilated cats with blood pressure held constant. The maximum effect of bicuculline in subseizure doses in control cats was to increase minute phrenic activity to 151 +/- 14% of preinfusion values. Infusion was continued until seizure activity was seen in the electroencephalogram. A 53% decrease of arterial O2 content resulted in a marked reduction of both peak phrenic amplitude and phrenic firing frequency to 16 and 64% of control values, respectively. Infusion of bicuculline while the level of hypoxia was maintained constant restored both peak phrenic amplitude and phrenic firing frequency to prehypoxic levels. The maximum effect of bicuculline was to increase minute phrenic activity to 123 +/- 13% of the prehypoxic value. These results suggest that although GABA has only a modest role in determining the output of the control phrenic neurogram, a significant portion of the phrenic depression that occurs during hypoxia can be attributed to inhibition of respiratory neurons by GABA.
我们通过监测膈神经电图对γ-氨基丁酸（GABA）拮抗剂荷包牡丹碱（0.01 mg·kg⁻¹·min⁻¹）全身输注的反应，评估了GABA作为缺氧性呼吸抑制潜在致病因素的作用。实验在分别处于对照条件下以及吸入一氧化碳导致等碳酸血症性脑缺氧期间进行，实验对象为麻醉、去肾小球、切断迷走神经、麻痹并进行机械通气且血压保持恒定的猫。在对照猫中，亚惊厥剂量的荷包牡丹碱的最大作用是使膈神经每分钟活动增加至输注前值的151±14%。持续输注直至脑电图出现癫痫活动。动脉血氧含量降低53%导致膈神经峰值幅度和放电频率显著降低，分别降至对照值的16%和64%。在维持缺氧水平恒定的同时输注荷包牡丹碱可使膈神经峰值幅度和放电频率恢复至缺氧前水平。荷包牡丹碱的最大作用是使膈神经每分钟活动增加至缺氧前值的123±13%。这些结果表明，尽管GABA在决定膈神经控制图的输出方面作用不大，但缺氧期间发生的膈神经抑制的很大一部分可归因于GABA对呼吸神经元的抑制。
