TY - JOUR
T1 - Effect of antagonism at central nervous system M3 muscarinic receptors on laryngeal chemoresponse
AU - Richardson, Brent E.
AU - Pernell, Kerri J.
AU - Goding, George
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
KW - Chemoreceptors
KW - Chemoreflex
KW - Laryngeal reflexes
KW - M3
KW - Muscarinic receptors
KW - Sudden infant death syndrome
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U2 - 10.1177/000348949710601107
DO - 10.1177/000348949710601107
M3 - Article
C2 - 9373082
AN - SCOPUS:0030666332
SN - 0003-4894
VL - 106
SP - 920
EP - 926
JO - Annals of Otology, Rhinology and Laryngology
JF - Annals of Otology, Rhinology and Laryngology
IS - 11
ER -