[Physiological basis for the use of muscarine antagonists in bronchopulmonary dysplasia].
The rationale for the use of muscarinic antagonists in bronchopulmonary dysplasia (BPD) is based on the physiology and pharmacology of airway smooth muscle, the pathology of BPD, and the response of infants with BPD to bronchodilators, in vivo and in vitro studies of airway smooth muscle of newborn animals and humans indicate that vagal efferent airway innervation and/or muscarinic receptors are functional at birth, as well as early in gestation. Current concepts regarding muscarinic receptor subtypes suggest that M3 receptors mediate airway smooth muscle contraction, M2 receptors are autoinhibitory and limit vagally-mediated bronchoconstriction, and M1 receptors may play a facilitatory role in ganglionic transmission. Muscarinic receptor subtypes appear to be functionally expressed at birth but may undergo developmental regulation. Infants with BPD have an elevated pulmonary resistance that is accompanied by hypertrophy of airway smooth muscle, b2-agonists cause bronchodilation in BPD as does atropine in infants recovering from severe BPD. The synthetic congener of atropine, ipratropium bromide (IPB) causes bronchodilation in ventilator-dependent infants with BPD in a dose-dependent fashion. Nebulized IPB causes a decrease in respiratory resistance that reaches a maximum of 20% at 175 mg. The bronchodilation seen with muscarinic antagonists suggests that part of the elevated resistance associated with BPD is due to increased muscarinic tone, presumably vagal in origin. When IPB is combined with salbutamol (0.04 mg) the response is increased in magnitude and duration; reaching a slightly larger decreases in resistance (26%) that is now accompanied by an increase in compliance (20%).(ABSTRACT TRUNCATED AT 250 WORDS)
Fisher
J T
JT
Département de physiologie, d'anesthésie et de pédiatrie de l'université Queen, Kingston, Ontario, Canada.
Froese
A B
AB
Brundage
K L
KL
D000818:Animals; D001993:Bronchodilator Agents / Q000627:therapeutic use; D001997:Bronchopulmonary Dysplasia / Q000188:drug therapy / Q000378:metabolism*; D004334:Drug Administration Schedule; D006801:Humans; D007231:Infant, Newborn; D009241:Ipratropium / Q000008:administration & dosage / Q000627:therapeutic use; D009130:Muscle, Smooth / Q000378:metabolism; D010277:Parasympathomimetics / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000627:therapeutic use; D012137:Respiratory System / Q000378:metabolism
D001993:Bronchodilator Agents; D010277:Parasympathomimetics; D009241:Ipratropium
Bases physiologiques de l'utilisation des antagonistes muscariniques dans les dysplasies bronchopulmonaires.