Effect of Antagonism at Central Nervous System M3 Muscarinic Receptors on Laryngeal Chemoresponse

Abstract

The laryngeal chemoresponse (LCR), comprising laryngeal adductor spasm, central apnea, and subsequent cardiovascular instability, is thought to be a factor in sudden infant death syndrome. A muscarinic subtype receptor, M3, appears to be involved in central respiratory drive and control. Both the duration of the LCR apnea and levels of M3 receptor messenger RNA in the brain stem change according to postnatal age. This study examined the effect of central nervous system antagonism at M3 receptors on the LCR with respect to animal age and dose of antagonist. Ten piglets in each of three age groups (group 1, 5 to 8 days; group 2, 18 to 21 days; and group 3, 40 to 43 days) received a series of four increasing doses of an M3 antagonist (p-fluoro-hexahydro-siladiphenidol) by intracerebral ventricle injection. The LCR was evoked at baseline and after each dose of antagonist. An effect on susceptible animals (groups 1 and 2) was evident by the second antagonist dose, and persisted for the remainder of the experiment (2 hours). At completion of the experiment, mean apnea duration had decreased in group 1 (61%, p < .05), and group 2 (57%, p < .05), but was unchanged in group 3 (<10%, p not significant). Length of mean baseline apneas correlated directly with degree of apnea shortening. The reduction is not attributable to changes in arterial Po2 or Pco2 or baseline respiratory rate. These results support an age-related influence on the LCR by M3 receptors in younger animals that decreases with maturation.