Sevoflurane enhances γ-aminobutyric acid type A receptor function and overall inhibition of inspiratory premotor neurons in a decerebrate dog model

被引:21
作者
Stucke, AG
Zuperku, EJ
Krolo, M
Brandes, IF
Hopp, FA
Kampine, JP
Stuth, EAE [1 ]
机构
[1] Zablocki Vet Affairs Med Ctr, Res Serv 151, Milwaukee, WI 53295 USA
[2] Med Coll Wisconsin, Milwaukee, WI 53226 USA
[3] Zablocki Vet Affairs Med Ctr, Res Serv, Milwaukee, WI 53295 USA
[4] Med Coll Wisconsin, Childrens Hosp Wisconsin, Dept Anesthesiol, Milwaukee, WI 53226 USA
关键词
D O I
10.1097/00000542-200507000-00012
中图分类号
R614 [麻醉学];
学科分类号
100217 [麻醉学];
摘要
Background: Inspiratory premotor neurons in the caudal ventral medulla relay excitatory drive to phrenic and inspiratory intercostal motoneurons in the spinal cord. These neurons are subject to tonic gamma-aminobutyric acid type A (GABA(A))ergic inhibition. In a previous study, 1 minimum alveolar concentration (MAC) sevoflurane depressed overall glutamatergic excitatory drive and enhanced overall GABA(A)ergic inhibitory drive to the neurons. This study investigated in further detail the effects of sevoflurane on GABA(A)ergic inhibition by examining postsynaptic GABAA receptor activity in these neurons. Methods: Studies were performed in decerebrate, vagotomized, paralyzed, and mechanically ventilated dogs during hypercapnic hyperoxia. The effect of 1 MAC sevoflurane on extracellularly recorded neuronal activity was measured during localized picoejection of the GABAA receptor antagonist bicuculline and the GABA(A) agonist muscimol. Complete blockade of GABAAergic inhibition by bicuculline allowed estimation of the prevailing overall inhibition of the neuron. The neuronal response to muscimol was used to assess the anesthetic effect on the postsynaptic GABAA receptor function. Results: One MAC sevoflurane depressed the spontaneous activity of 21 inspiratory premotor neurons by (mean +/- SD) 32.6 +/- 20.5% (P < 0.001). Overall excitatory drive was depressed 17.9 +/- 19.8% (P < 0.01). Overall GABAAergic inhibition was enhanced by 18.5 +/- 18.2% (P < 0.001), and the postsynaptic GABA(A) receptor function was increased by 184.4 +/- 121.8% (n = 20; P < 0.001). Conclusion: One MAC sevoflurane greatly enhanced GABA, receptor function on inspiratory premotor neurons and increased overall synaptic inhibition but to a smaller extent, indicating that the presynaptic inhibitory input was also reduced. Therefore, die anesthetic depression of spontaneous inspiratory premotor neuronal activity by 1 MAC sevollurane in vivo is due to a combined effect on the two major ionotropic synaptic neurotransmitter systems with a decrease in overall glutamatergic excitation and a strong enhancement of postsynaptic GABAA receptor function.
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页码:57 / 64
页数:8
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