Lung tissue behaviour in the mouse during constriction induced by
methacholine and endothelin-1.
Nagase, Takahide, Hirotoshi Matsui, Tomoko Aoki, Yasuyoshi Ouchi, and
Yoshinosuke Fukuchi.
Department of Geriatrics, Faculty of Medicine, University of Tokyo,
Tokyo, Japan
APStracts 3:0384A, 1996.
Recently, mice have been extensively employed to investigate the
pathogenesis of pulmonary disease, since appropriate murine models
including transgenic mice are being increasingly developed. However,
little information about the lung mechanics of mice is currently
available. We questioned whether lung tissue behaviour and the
coupling between dissipative and elastic processes, hysteresivity
(_), in mice would be different from those in the other species. To
address this question, we investigated whether tissue resistance and
_ in mice would be affected by varying lung volume, constriction
induced by methacholine (MCh) and endothelin-1 (ET-1), and high lung
volume challenge during induced constriction. From measured tracheal
flow and tracheal and alveolar pressure in open-chested ICR mice
during mechanical ventilation (VT= 8ml/kg, f=2.5Hz), we calculated
resistance of lung (RL), tissue (Rti) and airway (Raw), lung
elastance (EL), and _ (=2[pi]fRti/EL). Under baseline conditions,
increasing levels of end-expiratory transpulmonary pressure (PL)
decreased Raw and increased Rti. The administration of aerosolized
MCh and iv ET-1 increased RL, Rti, Raw, and EL in a dose dependent
manner. Rti increased from 0.207+/-0.010 to 0.570+/-0.058 cmH2O/ml/s
after 10-7 mol/kg ET-1 (P<0.01). After induced constriction,
increasing PL decreased Raw. However, _ was not affected by changing
lung volume, constriction induced by MCh and ET-1, or high lung
volume challenge during induced constriction. These observations
suggest that 1) hysteresivity is stable in mice regardless of various
conditions, 2) Rti is an important fraction of RL and increases after
induced constriction, 3) mechanical interdependence may affect airway
smooth muscle shortening in this species. In mammalian species
including mice, analysis of the hysteresis may indicate that both Rti
and EL essentially respond to a similar degree.
Received 7 March 1996; accepted in final form 2 August 1996.
APS Manuscript Number A229-6.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996