Limitation of airway smooth muscle shortening by cartilage stiffness and lung elastic recoil in rabbits.
Airway smooth muscle can contract to 20% of its starting length when stimulated maximally and allowed to contract isotonically in vitro. In vivo airway smooth muscle contraction of this degree would result in widespread airway closure. We hypothesized that elastic loads related to cartilage stiffness and lung parenchyma-airway interdependence limit in vivo airway smooth muscle shortening. We measured pulmonary resistance in anesthetized tracheostomized New Zealand White rabbits before and after intravenous treatment with papain in a concentration that produced generalized cartilage softening. Papain treatment caused a significant increase in pulmonary resistance that was completely reversed by application of 4 cmH2O positive end-expiratory pressure and that was partially reversed by vagotomy. Papain pretreatment also resulted in a substantial alteration in the pulmonary resistance-dose relationship to intravenously administered acetylcholine. In addition, maximal resistance after the highest concentration of acetylcholine was greater in papain-treated animals than in the control animals, but the position of the dose-response relationship was not shifted (i.e., there was no change in the effective dose causing 50% maximal response). Application of 4 cmH2O positive end-expiratory pressure in untreated animals resulted in a marked decrease in the bronchoconstriction produced by an effective dose of acetylcholine causing 50% of maximal response, whereas application of 4 cmH2O negative end-expiratory pressure resulted in a marked enhancement of the bronchoconstrictor response to the same intravenous dose of acetylcholine. We conclude that cartilage elasticity and lung recoil are important determinants of the ability of airway smooth muscle to shorten and produce airway narrowing in vivo.
Moreno
R H
RH
Pulmonary Research Laboratory, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
Lisboa
C
C
Hogg
J C
JC
Paré
P D
PD
D000109:Acetylcholine / Q000494:pharmacology; D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D002356:Cartilage / Q000187:drug effects / Q000502:physiology*; D004548:Elasticity; D007551:Isotonic Contraction / Q000502:physiology; D008168:Lung / Q000502:physiology*; D008176:Lung Volume Measurements; D008688:Methacholine Compounds / Q000494:pharmacology; D009130:Muscle, Smooth / Q000502:physiology*; D010206:Papain / Q000494:pharmacology; D011175:Positive-Pressure Respiration; D011817:Rabbits; D014628:Vagotomy
D008688:Methacholine Compounds; D010206:Papain; D000109:Acetylcholine