Responses of laryngeal capsaicin-sensitive receptors to volatile anesthetics in anesthetized dogs
Introduction
Induction of anesthesia with volatile anesthetics is sometimes complicated by the exertion of excessive protective or defensive upper airway reflexes such as cough, apnea, laryngospasm and secretion (Drummond, 1988, Drummond, 1993). Clinically, these have been presumed to be caused by irritation of the airway mucosa, the degree of which varies with anesthetic and anesthetic depth (Doi and Ikeda, 1993). For example, isoflurane and enflurane are known to cause relatively strong airway irritation when administered anesthesia by face mask (Sampaio et al., 1989, Yurino and Kimura, 1992Doi and Ikeda 1993). Halothane is a slightly milder irritant to airways than are isoflurane and enflurane, but it can produce similar reflex actions when inhaled at high concentrations (Doi and Ikeda, 1993, Yurino and Kimura, 1993). On the other hand, sevoflurane, a new halogenated volatile anesthetic recently approved for clinical use in Japan, the United States, and the United Kingdom, is relatively non-irritating to airways, providing a rapid and smooth onset of anesthesia coupled with a lower blood-gas solubility coefficient (Yurino and Kimura 1992Yurino and Kimura 1993Muzi et al., 1996).
The larynx is a potent reflexogenic region of the upper airway that is rich in sensory afferents and that elicits various reflexes to protect the lower airway and lung (Widdicombe et al., 1988Sant'Ambrogio et al., 1995). Several studies have revealed that the larynx is a possible source of airway irritation by volatile anesthetics. Sant'Ambrogio et al. (1993)suggested that halothane administered into the isolated upper airway remarkably depressed ventilation in newborn dogs, an effect which was greatly diminished by superior laryngeal nerve (SLN) section. Nishino et al. (1993)pointed out that halogenated volatile anesthetics, especially halothane, stimulated laryngeal irritant and cold receptors in adult dogs.
In the larynx, there is a type of receptor which can be activated by a nociceptive chemical stimulus such as capsaicin (CAPS), which produced marked cardiorespiratory responses like apnea, cough, bradycardia and hypertension in dogs (Mutoh et al., 1997), rats (Palecek et al., 1990, Hishida et al., 1996), and guinea pigs (Tsubone et al., 1991). Numerous and extensive studies have been conducted on the pulmonary or bronchial CAPS-sensitive afferents to chemical irritants including volatile anesthetics (Coleridge and Coleridge, 1984, Coleridge and Coleridge, 1994). However, only a few of these attempts have targeted the larynx, and laryngeal CAPS-sensitive receptors have thus far been identified only in guinea pigs (Tsubone et al., 1991).
The aims of this study were to: (1) identify the laryngeal CAPS-sensitive receptor; and (2) evaluate its response to volatile anesthetics in the dog. In addition, we also compared the responses of CAPS-sensitive receptors with those of irritant receptors.
Section snippets
General
Fifteen healthy beagle dogs (eight males and seven females) were used in this study. Their mean age was 13.6-months-old (ranging from 10 to 18 months) and their mean body weight 9.7 kg (ranging from 7.6 to 14.0 kg). Food was withheld at least 12 h before the experiments. This study was conducted under guidelines provided by the Animal Care Committee of the Graduate School of Agricultural and Life Sciences, The University of Tokyo.
Anesthesia was induced with thiopental sodium (25 mg/kg), then
Laryngeal CAPS-sensitive receptors
Single unit activities were recorded from a total of 30 receptors with an irregular discharge which did not have a respiratory modulation. Fifteen receptors (15/30, 50%) were stimulated by CAPS; 11 receptors were stimulated by only CAPS (‘CAPS-sensitive’ receptors: Table 1; Fig. 2), and four receptors were clearly stimulated by water and slightly by CAPS (Table 2 #1–4; Fig. 3a). The remaining 15 receptors were stimulated by only water and had no response to CAPS (Table 2 #5–19; Fig. 3b).
All but
Laryngeal CAPS-sensitive receptors in the dog
In this study, the presence of laryngeal CAPS-sensitive receptors was ascertained in dogs through the topical application of CAPS into the laryngeal lumen. These receptors were clearly distinguished from irritant receptors by their predominant responsiveness to CAPS and lack of water response. These findings well coincided with those of CAPS-sensitive receptors in guinea pigs (Tsubone et al., 1991). Capsaicin is a selective stimulant for C-fiber endings and some A-δ fiber endings (Holzer, 1991
Acknowledgements
This study was supported in part by a Research Fellowship of the Japan Society for the Promotion of Science for Young Scientists.
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