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GENERAL ARTICLES

Interaction Between Volatile Anesthetics and Hypoxia in Porcine Tracheal Smooth Muscle

Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Japan

Address correspondence and reprint requests to Michiaki Yamakage, MD, PhD, Department of Anesthesiology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido 060-8543, Japan. Address e-mail to yamakage{at}sapmed .ac.jp.

We investigated the direct interaction between the volatile anesthetics, isoflurane and sevoflurane, and hypoxia in porcine tracheal smooth muscle in vitro by simultaneously measuring muscle tension and intracellular concentration of free Ca²⁺ ([Ca²⁺]_i). Muscle tension was measured by using an isometric transducer, and [Ca²⁺]_i was measured by using fura-2, an indicator of Ca²⁺. Under the condition of bubbling with 95% O₂/5% CO₂, [Ca²⁺]_i was increased by 1 µM carbachol with a concomitant contraction. Volatile anesthetics significantly inhibited both carbachol-induced muscle contraction and increase in [Ca²⁺]_i. Hypoxia bubbled with 95% N₂/5% CO₂ inhibited the muscle contraction by 30% with an increase in [Ca²⁺]_i by 20%. Exposure to hypoxia substantially enhanced the inhibitory effects of these anesthetics on carbachol-induced muscle contraction, whereas the decreases in [Ca²⁺]_i were significantly prevented by hypoxia. Under Ca²⁺-free conditions, hypoxia significantly decreased the muscle contraction by 20%; however, it still increased [Ca²⁺]_i by 15%. Exposure to the anesthetics significantly enhanced the inhibitory effect of hypoxia on the muscle contraction; however, it appeared to have little effect on [Ca²⁺]_i. Hypoxia inhibits airway smooth muscle contraction independently of intracellular Ca²⁺, and it substantially potentiates the inhibitory effects of volatile anesthetics on airway smooth muscle contraction.

Implications: Hypoxia inhibits agonist-induced tracheal smooth muscle contraction with an increase in free Ca²⁺ [Ca²⁺]_i, which comes from intracellular Ca²⁺ stores. Hypoxia also potentiates the inhibitory effect of volatile anesthetics on airway smooth muscle contraction. Conversely, there is a possibility that the treatment of asthmatic patients with oxygen partially attenuates the inhibitory effect of volatile anesthetics on airway smooth muscle contractility.

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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