Spontaneous Peristaltic Airway Contractions Propel Lung Liquid through the Bronchial Tree of Intact and Fetal Lung Explants

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Abstract
Spontaneous contractions of the fetal airways are a well recog- nized but poorly characterized phenomenon. In the present study spontaneous narrowing of the airways was analyzed in freshly isolated lungs from early to late gestation in fetal pigs and rabbits and in cultured fetal mouse lungs. Propagating waves of contraction traveling proximal to distal were ob- served in fresh lungs throughout gestation which displaced the lung liquid along the lumen. In the pseudoglandular and canalicular stages (fetal pigs) the frequency ranged from 2.3 to 3.3 contractions/min with a 39 to 46% maximum reduction of lumen diameter. In the saccular stage (rabbit) the frequency was 10 to 12/min with a narrowing of z 30%. In the organ cul- tures the waves of narrowing started at the trachea in whole lungs, or at the main bronchus in lobes (5.2 6 1.5 contrac- tions/min, 22 6 8% reduction of lumen diameter), and as they proceeded distally along the epithelial tubes the luminal liquid was shifted toward the terminal tubules, which expanded the endbuds. As the tubules relaxed the flow of liquid was re- versed. Thus the behavior of airway smooth muscle in the fetal lung is phasic in type (like gastrointestinal muscle) in contrast to that in postnatal lung, where it is tonic. An intraluminal pos- itive pressure of 2.33 6 0.77 cm H 2 O was recorded in rabbit fe- tal trachea. It is proposed that the active tone of the smooth muscle maintains the positive intraluminal pressure and acts as a stimulus to lung growth via the force exerted across the air- way wall and adjacent parenchyma. The expansion of the com- pliant endbuds by the fluid shifts at the airway tip may pro- mote their growth into the surrounding mesenchyme. Spontaneous narrowing and relaxation of the airways in