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Aerosolized surfactant inhibits acetylcholine-induced bronchoconstruction in rats


American Journal of Respiratory and Critical Care Medicine 149 (1994), Nr.4, S.A97
ISSN: 1073-449X
American Lung Association (International Conference) <1994, Boston/Mass.>
Fraunhofer ITA ( ITEM) ()
Acetylcholine; rat; surface active agents

Pulmonary surfactant is important for the stability of the alveoli and the small airways and has been shown to modulate the function of respiratory inflammatory cells and macrophages. Intratracheal pretreatment with surfactant is cabable of inhibiting the antigen-induced bronchoconstriction in sensitized guinea pigs (Becher, Biomed. Biochim. Acta 44, 1985) In addition, nebulized surfactant was shown to improve respiratory function in asthmatic patients ( Kurashima et al., Jpn. J. Allergol. 40, 1991). The aim of this study was to investigate the effect of aerosolized surfactant on receptor-mediated bronchoconstriction in comparison to inhaled terbuline in rats. Anaesthetized intubated spontaneously breathing Wistar-rats (350-450 g) were either pretreated with aerosolized vehicle ( Ringer's solution, "control", n=9), terbutaline (0,027% w/v, "terbutaline*1", n=8 and 0,054% w/v, "terbutaline*2", n=5) or surfactant ( Alveofact®, "alveofact", n=8), respectively using a jet nebulizer for eff icent aerosol generation (Bronchy-H, Fraunhofer Institute).Animals were then challenged by aerosolized acetylcholine (ACh) in a standardized computer-controlled manner to elicit receptor-mediated bronchoconstriction. Aerosol concentration was monitored continuously by photometer. Particle size distribution was determined for all aerosols to estimate the amount of aerosol deposited in the lungs. Spontaneous respiratory function parameters were measured using whole-bodyplethysmography. The following parameters were calculated and recorded before pretreatment and prior and after the ACh-challenge: airway resistance (Raw), compliance (C), tidal volume (Vt), minute volume (MV) and breathing frequency (f). There was no significant difference in baseline values prior and after pretreatment between the treatment groups. ACh-challenge induced a significant bronchoconstriction with an increase of Raw in control of 64,0+-7,7% (mean +- SEM), whereas the increase of Raw in terbutaline*1, terbutali n e*2 and alveofact was 45,2+-8,4%, 36,0+- 6,8% and 34,4+-4,9%, respectively. For terbutaline*2 and alveofact this difference was significant compared to control (P<0,05, ANOVA followed by t-test). The other spontaneous respiratory function parameters were not significantly different between the treatment groups. In conclusion, both alveofact and terbutaline reduce the ACh-induced bronchoconstriction in rats. Further studies are needed to investigate the underlying mechanisms of the surfactant effect. Alveofact was a generous gift by Dr. K. Thomae GmbH, Biberach, Germany.