Ketamine inhibits inspiratory-evoked γ-aminobutyric acid and glycine neurotransmission to cardiac vagal neurons in the nucleus ambiguus

Xin Wang, Zheng Gui Huang, Olga Dergacheva, Evguenia Bouairi, Christopher Gorini, Christopher Stephens, Michael C. Andresen, David Mendelowitz

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Background: Ketamine can be used for perioperative pain management as well as a dissociative anesthetic agent in emergency situations. However, ketamine can induce both cardiovascular and respiratory depression, especially in pediatric patients. Although ketamine has usually been regarded as sympathoexcitatory, recent work has demonstrated that ketamine has important actions on parasympathetic cardiac vagal efferent activity. The current study tests the hypothesis that ketamine, at clinical relevant concentrations, alters central cardiorespiratory interactions in the brainstem and, in particular, the inspiration-evoked increase in γ-aminobutyric acid-mediated and glycinergic neurotransmission to parasympathetic cardiac efferent neurons. Methods: Cardiac vagal neurons were identified by the presence of a retrograde fluorescent tracer. Respiratory evoked γ-aminobutyric acid-mediated and glycinergic synaptic currents were recorded in cardiac vagal neurons using whole cell patch clamp techniques while spontaneous rhythmic respiratory activity was recorded simultaneously. Results: Ketamine, at concentrations from 0.1 to 10 μM, evoked a concentration-dependent inhibition of inspiratory burst frequency. Inspiration-evoked γ-aminobutyric acid-mediated neurotransmission to cardiac vagal neurons was inhibited at ketamine concentrations of 0.5 and 1 μM. The increase in glycinergic activity to cardiac vagal neurons during inspiration was also inhibited at ketamine concentrations of 0.5 and 1 μM. Conclusions: At clinically relevant concentrations (0.5 and 1 μM), ketamine alters central respiratory activity and diminishes both inspiration-evoked γ-aminobutyric acid-mediated and glycinergic neurotransmission to parasympathetic cardiac efferent neurons. This reduction in inhibitory neurotransmission to cardiac vagal neurons is likely responsible for the compromised respiratory sinus arrhythmia that occurs with ketamine anesthesia.

Original languageEnglish (US)
Pages (from-to)353-359
Number of pages7
JournalAnesthesiology
Volume103
Issue number2
DOIs
StatePublished - Aug 2005

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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