Ketamine inhibits inspiratory-evoked gamma-aminobutyric acid and glycine neurotransmission to cardiac vagal neurons in the nucleus ambiguus.
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 gamma-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 gamma-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 microM, evoked a concentration-dependent inhibition of inspiratory burst frequency. Inspiration-evoked gamma-aminobutyric acid-mediated neurotransmission to cardiac vagal neurons was inhibited at ketamine concentrations of 0.5 and 1 microM. The increase in glycinergic activity to cardiac vagal neurons during inspiration was also inhibited at ketamine concentrations of 0.5 and 1 microM.


CONCLUSIONS
At clinically relevant concentrations (0.5 and 1 microM), ketamine alters central respiratory activity and diminishes both inspiration-evoked gamma-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.
Wang
Xin
X
Department of Pharmacology, George Washington University, DC 20037, USA.
Huang
Zheng-Gui
ZG
Dergacheva
Olga
O
Bouairi
Evguenia
E
Gorini
Christopher
C
Stephens
Christopher
C
Andresen
Michael C
MC
Mendelowitz
David
D
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005998:Glycine / Q000378:metabolism*; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D014630:Vagus Nerve / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D005680:gamma-Aminobutyric Acid; D007649:Ketamine; D005998:Glycine