Transient Receptor Potential A1 Activation Prolongs Isoflurane Induction Latency and Impairs Respiratory Function in Mice

Authors: Fengxian Li, M.D.; Changxiong J. Guo, B.A.; Cheng-Chiu Huang, Ph.D.; Guang Yu, Ph.D.; Sarah M. Brown, Ph.D.; Shiyuan Xu, M.D.; Qin Liu, Ph.D.

Published in The Journal of the American Society of Anesthesiologists on 1 2015.
Background: Isoflurane is a potent volatile anesthetic; however, it evokes airway irritation and neurogenic constriction through transient receptor potential (TRP) A1 channels and sensitizes TRPV1 channels, which colocalizes with TRPA1 in most of the vagal C-fibers innervating the airway. However, little is known about the precise effects of these two channels on the respiratory function during isoflurane anesthesia.

Methods: By using a rodent behavioral model and whole-body plethysmograph, the authors examined the response of Trpa1−/− andTrpv1−/− mice to isoflurane anesthesia and monitored their respiratory functions during anesthesia.

Results: This study showed that Trpa1−/− mice (n = 9), but not Trpv1−/−mice (n = 11), displayed a shortened induction latency compared with wild-type mice (n = 10) during isoflurane anesthesia (33 ± 2.0 s in wild-type and 33 ± 3.8 s in Trpv1−/− vs. 17 ± 1.8 in Trpa1−/− at 2.2 minimum alveolar concentrations). By contrast, their response to the nonpungent volatile anesthetic sevoflurane is indistinguishable from wild-type mice (24 ± 3.6 s in wild-type vs. 26 ± 1.0 s in Trpa1−/− at 2.4 minimum alveolar concentrations). The authors discovered thatTrpa1−/− mice inhaled more anesthetic but maintained better respiratory function. Further respiration pattern analysis revealed that isoflurane triggered nociceptive reflexes and led to prolonged resting time between breaths during isoflurane induction as well as decreased dynamic pulmonary compliance, an indicator of airway constriction, throughout isoflurane anesthesia in wild-type and Trpv1−/− mice, but not in Trpa1−/− mice.

Conclusion: Activation of TRPA1 by isoflurane negatively affects anesthetic induction latency by altering respiratory patterns and impairing pulmonary compliance.