Desflurane‐Induced Coughing in Conscious Guinea Pigs is Mediated through TRPA1

Abstract

Desflurane is widely used for induction and maintenance of anesthesia, and is associated with a high incidence of perioperative coughing. Desflurane has been shown to activate TRPA1 in vitro and increase total lung resistance in anesthetized guinea pigs that could be mitigated with a selective TRPA1 antagonist.PurposeTo evaluate the mechanism of desflurane‐induced coughing in conscious guinea pigs during anesthetic induction.MethodsGuinea pigs were placed into a transparent chamber where flow rate, pressure, audio and video were recorded. Animals were induced with 1 MAC (6.4%) desflurane or challenged with a selective agonist for TRPV1 (citric acid, 1 M) or TRPA1 (AITC, 80 mM) with or without pre‐treatment with a selective antagonist for TRPV1 (BCTC, 3 mg/kg IP) or TRPA1 (HC‐030031, 300 mg/kg IP). The number of coughs over a fixed, 5‐min exposure period was recorded.ResultsDesflurane caused 4.9 coughs vs. 0 for the carrier air. AITC caused 10.7 coughs vs. 5.8 when pretreated with HC‐030031 (p<0.05). Citric acid caused 12.4 coughs vs. 3.2 when pre‐treated with BCTC (p<0.002). HC‐030031 markedly attenuated desflurane‐induced coughing (4.3 vs. 1.2, p<0.08) whereas BCTC had no effect (5.4 vs. 4.0, p=0.13).ConclusionDesflurane‐induced coughing in conscious guinea pigs appears to be mediated through activation of TRPA1. Supported by Baxter Healthcare Corporation.