Subject(s)
Bone Lengthening/rehabilitation , Exercise Therapy/methods , External Fixators , Bone Lengthening/adverse effects , Bone Lengthening/methods , Contracture/etiology , Contracture/prevention & control , Contracture/therapy , External Fixators/adverse effects , Extremities/growth & development , Extremities/surgery , Humans , Limb Deformities, Congenital , Range of Motion, ArticularABSTRACT
An in vitro preparation was developed to study vagus nerve-stimulated (preganglionic) and field-stimulated (post-ganglionic) contraction of the rabbit main stem bronchus and to compare the inhibitory effects of muscarinic antagonists on that contraction. The maximal contractile responses (20 V, 0.5 ms, 64 Hz) for either field or vagal stimulation were completely abolished by atropine (60 nM). Hexamethonium (0.1 mM) abolished the response to vagal stimulation but did not affect the field-stimulated response. To compare the effectiveness of atropine and pirenzepine as antagonists at the nerve-smooth muscle junction, inhibition studies of field-stimulated contractions were performed. Pirenzepine was 102- to 178-fold less potent than atropine when compared at the inhibitory concentration of antagonist that produced 25, 50, and 75% inhibition (IC25, IC50, and IC75, respectively), indicating that the muscarinic receptor at the nerve-smooth muscle junction is a muscarinic receptor with low affinity for pirenzepine (M2 subtype). Atropine had similar inhibitory effects on vagal- and field-stimulated contractions. In contrast, pirenzepine was more potent in inhibiting vagally stimulated contraction than field-stimulated contraction, especially at the IC25 where pirenzepine was only 8- to 22-fold less potent than atropine in inhibiting vagally stimulated contraction. These data suggest that an M1 subtype of muscarinic receptor modulates excitatory neurotransmission through bronchial parasympathetic ganglia.
Subject(s)
Bronchi/physiology , Receptors, Muscarinic/physiology , Vagus Nerve/physiology , Animals , Atropine/pharmacology , Bronchi/drug effects , Electric Stimulation , Female , In Vitro Techniques , Male , Muscle Contraction/drug effects , Parasympatholytics/pharmacology , Pirenzepine/pharmacology , Rabbits , Receptors, Muscarinic/drug effectsABSTRACT
The development of bronchial hyperresponsiveness to cholinergic agents in relation to antigen sensitization and repeated antigen challenge was investigated in a rabbit model. Rabbits immunized to produce preferentially specific IgE antibodies had a modest enhancement of their bronchoconstrictive response (measured as an increase in pulmonary resistance) to aerosolized methacholine compared to sham-immunized and unimmunized controls. A further enhancement was observed subsequent to a series of seven antigen challenges given transtracheally, such that the geometric mean dose of methacholine required to increase pulmonary resistance by 100% (PD100 RL) was 89 cumulative breath units (CBU) compared to 372 CBU for sham-immunized controls and 871 CBU for unimmunized controls (p less than 0.05 for ANOVA). Although methacholine also decreased dynamic compliance, the changes were not different among the three groups. Isolated intrapulmonary bronchi from the three groups did not differ in log concentration of methacholine yielding a half-maximal contraction (log EC50). The range of EC50 values was 15-fold compared to a 90-fold range of PD100 RL. In vivo cholinergic responsiveness of the pupillary muscle did not correlate with bronchial responsiveness. Thus, pulmonary antigen challenge of IgE-producing rabbits produced a marked increase in bronchial responsiveness which did not correlate with in-vitro bronchial responsiveness or with in vivo pupillary responsiveness.
