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ANESTHETIC PHARMACOLOGY

Interactions of Volatile Anesthetics with Cholinergic, Tachykinin, and Leukotriene Mechanisms in Isolated Guinea Pig Bronchial Smooth Muscle

C.U. Wiklund, MD PhD^*, U. Lindsten, MD^*, S. Lim, MD, and S.G.E. Lindahl, MD PhD^*

*Department of Anesthesiology and Intensive Care Medicine, Karolinska Hospital and Institute, Stockholm, Sweden; and Division of Pediatric Cardiology, University of Michigan, Ann Arbor

Address correspondence and reprint requests to Claes U. Wiklund, MD, PhD, Department of Anesthesiology and Intensive Care, Karolinska Hospital, S-171 76 Stockholm, Sweden. Address e-mail to claes.wiklund{at}ks.se

We studied relaxation of airway smooth muscle by sevoflurane, desflurane, and halothane in isolated guinea pig bronchi. Ring preparations were mounted in tissue baths filled with physiological salt solution and continuously aerated with 5% CO₂ in oxygen. Electrical field stimulation induced contractions sensitive to tetrodotoxin, indicating nerve-mediated responses. These consisted of an atropine-sensitive cholinergic phase and a nonadrenergic noncholinergic (NANC) phase sensitive to SR48968, a neurokinin-2 receptor antagonist. Anesthetics were added to the gas aerating the tissue baths. Sevoflurane and desflurane at 1.0 minimum alveolar anesthetic concentration and halothane at 1.0–2.0 minimum alveolar anesthetic concentrations inhibited both cholinergic and NANC contractions to electrical field stimulation. None of the anesthetics affected responses to exogenously applied neurokinin A, a likely mediator of NANC contractions, suggesting prejunctional inhibition of NANC neurotransmission. The anesthetics did not affect the initiation of contractile responses to leukotriene C₄ (LTC₄), a mediator of asthmatic bronchoconstriction. However, sevoflurane and desflurane both relaxed bronchi in a steady-state contraction achieved by LTC₄. Surprisingly, halothane did not relax LTC₄ contractions. Concerning LTC₄-elicited bronchoconstriction, sevoflurane and desflurane were more potent airway smooth muscle relaxants in vitro.

IMPLICATIONS: Halothane, sevoflurane, and desflurane attenuated airway smooth muscle tone via inhibition of cholinergic and nonadrenergic noncholinergic neurotransmission. Sevoflurane and desflurane reduced leukotriene C₄-induced bronchoconstriction, whereas halothane did not. This indicates a beneficial role for sevoflurane and desflurane in asthmatics.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999