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British Journal of Anaesthesia, Vol 75, Issue 1 71-79, Copyright © 1995 by The Board of Management and Trustees of the British Journal of Anaesthesia

LABORATORY INVESTIGATIONS

Comparison of the pharmacodynamics of ketamine in the isolated neonatal and adult porcine airway

P. E. Hodgson, K. Rehder and D. J. Hatch
Department of Anaesthesia, Intensive Therapy and Respiratory Medicine, Institute of Child Health, 30 Guilford Street, London WC1N 1EH; Mayo Clinic, Rochester, MN 55905, USA

Ketamine inhibits contractions of adult airway smooth muscle by actions both within the smooth muscle cell and the vagal intramural ganglia. Its effects in the neonate are unknown, as physiological changes occur after birth in both of these structures. Isolated trachealis muscle strips from neonatal and adult pigs were contracted selectively by stimulation of the vagal intramural ganglia using dimethyl-phenyl- piperazinium (DMPP), the post-ganglionic vagus nerve using electrical field stimulation (EFS) and the smooth muscle cell itself using acetylcholine (ACh) in the presence of tetrodotoxin. The inhibitory effects of clinical concentrations of ketamine at each site were compared both within and between age groups. At both ages, ketamine 10(- 4) mol litre-1 abolished (P < or = 0.001) and ketamine 10(-5) mol litre- 1 attenuated (P < or = 0.001) the contractile responses to DMPP at the intramural ganglia. The inhibitory effect of ketamine 10(-4) mol litre- 1 on ACh responses at the smooth muscle cell was greater in neonatal preparations (P = 0.025). Furthermore, only neonatal EFS and ACh responses were attenuated by ketamine 10(-5) mol litre-1 (P = 0.04 and P = 0.03). Ketamine 10(-4) mol litre-1 attenuated EFS responses in both age groups (P < or = 0.001). In the adult, this was similar to the attenuation of ACh responses (mean 56 (SD 15) % vs 45 (18) %; P = 0.1), but in neonatal preparations EFS responses were more attenuated than ACh responses (97 (6) % vs 63 (16) %, respectively; P = 0.006), suggesting an additional inhibitory effect of ketamine on the postganglionic nerve of the neonate.
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