Advertisement

Laudanosine has No Effects on Respiratory Activity but Induces Non-Respiratory Excitement Activity in Isolated Brainstem-Spinal Cord Preparation of Neonatal Rats

  • Shigeki Sakuraba
  • Yuki Hosokawa
  • Yuki Kaku
  • Junzo Takeda
  • Shun-ichi Kuwana
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 669)

Abstract

Laudanosine, a degradation of neuomuscular blocking agent atracurium, crosses the blood-brain barrier and is indicted to trigger seizures at high concentration. In Xenopus Oocytes expressing nicotinic acetylcholine receptors (nAChRs), laudanosine has activating and inhibiting effects on nAChRs depending on its concentration. nAChRs is related to respiratory activities and thus, in the present study, we analyzed effects of laudanosine on central respiratory activities using isolated brainstem-spinal cord preparation of neonatal rats. The rhythmic inspiratory burst activity of the C4 spinal ventral root was recorded using a glass suction electrode as an index of respiratory rate. After superfusion with mock cerebrospinal fluid (CSF), the preparation was superfused with mock CSF containing laudanosine 1, 10 or 100 μM for 60 minutes. Laudanosine 1, 10 and 100 μM (n = 10 in each) did not induce any effects on C4 respiratory rate. In all 10 preparations, laudnosine 100 μM induced non-respiratory excitement activities that are possibly same as seizure observed in vivo study.

Keywords

Respiratory Activity Neuromuscular Blocking Agent Vecuronium Bromide Neuronal nAChRs Inspiratory Discharge 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This study was supported by a Grant-in-Aid for Young Scientist (SS).

References

  1. Beemer, G.H., Bjorksten, A.R., Dawson, P.J., and Crankshaw, D.P. (1989) Production of laudanosine following infusion of atracurium in man and its effects on awakening. Br. J. Anaesh. 63, 76–80.CrossRefGoogle Scholar
  2. Chapple, D.J., Mille, A.A., Ward, J.B., and Wheathey, P.L. (1987) Cardiovascular and neurological effects of laudanosine. Studies in mice and rats, and in conscious and anaesthetized dogs. Br. J. Anaesth. 59, 218–225.CrossRefPubMedGoogle Scholar
  3. Chiodini, F., Charpantier, E., Muller, D., Tassonyi, F., Fuchs-Buder, T., and Bertrand, D. (2001) Blockade and activation of the human neuronal nicotinic acetylcholine receptors by atracurium and laudanosine. Anesthesiology 94, 643–651.CrossRefPubMedGoogle Scholar
  4. Eddleston, J.M., Harper, N.J., Pollard, B.J., Edwards, D., and Gwonnutt, C.L. (1989) Concentration of atracurium and laudanosine in cerebrospinal fluid and plasma during intracranial surgery. Br. J. Anaesth. 63, 525–530.CrossRefPubMedGoogle Scholar
  5. Fodale, V., and Santamaria, L.B. (2002) Laudanosine, an atracurium and cisatracurium metabolite. Eur. J. Anaesthesiol. 19, 466–473.PubMedGoogle Scholar
  6. Hatori, E., Sakuraba, S., Kashiwagi, M., Kuribayashi, J., Tsujita, M., Hosokawa, Y., Takeda, J., and Kuwana, S. (2006) Association of nicotinic acetylcholine receptors with central respiratory control in isolated brainstem-spinal cord preparation of neonatal rats. Biol. Res. 39, 321–330.CrossRefPubMedGoogle Scholar
  7. Lanier, W.L., Milde, J.H., and Michenfelder, J.D. (1985) The cerebral effects of pancuronium and atracurium in halothane-anesthetized dogs. Anesthesiology 63, 1236–1241.Google Scholar
  8. Onimaru, H., Ballanyi, K., and Richter, D.W. (1996) Calcium-dependent responses in neurons of the isolated respiratory network of newborn rats. J. Physiol. 491, 677–695.PubMedGoogle Scholar
  9. Sakuraba, S., Kuwana, S., Ochiai, R., Okada, Y., Kashiwagi, M., Hatori, E., and Takeda, J. (2003) Effects of neuromuscular blocking agents on central respiratory control in the isolated brainstem-spinal cord of neonatal rat. Neurosci. Res. 47, 289–298.CrossRefPubMedGoogle Scholar
  10. Tassonyi, E., Fathi, M., Hughes, G.J., Chiodini, F., Bertrand, D., Muller, D., and Fuchs-Buder, T. (2002) Cerebrospinal fluid concentrations of atracurium, laudanosine and vecuronium following clinical subarachnoid hemorrhage. Acta. Anaesthesiol. Scand. 46, 1236–1241.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Shigeki Sakuraba
    • 1
  • Yuki Hosokawa
    • 1
  • Yuki Kaku
    • 2
  • Junzo Takeda
    • 1
  • Shun-ichi Kuwana
    • 2
  1. 1.Department of AnesthesiologyKeio UniversityTokyoJapan
  2. 2.Department of PhysiologyUekusa UniversityChibaJapan

Personalised recommendations