Contribution of airway closure to chronic postbronchiolitis airway dysfunction in rats.
Genetically susceptible Brown Norway rats develop a chronic asthmalike syndrome after recovering from viral bronchiolitis at an early age. We hypothesized that airway closure is an important mechanism of airflow obstruction in postbronchiolitis rats. Rats were studied 8-12 wk after inoculation with Sendai virus or sterile vehicle at 3-4 wk of age. Under light pentobarbital anesthesia, rats were instrumented with an orotracheal catheter and an esophageal pressure monitor and placed in a total body plethysmograph. Lung volumes and forced-expiratory maneuvers were measured using the Boyle's law method and software-controlled valving of positive and negative pressures to elicit lung inflations and rapid deflations; pulmonary resistance was measured during spontaneous tidal breathing; and quasi-static pressure-volume curves were obtained with passive inflations and deflations in fully anesthetized, paralyzed rats. Compared with controls, the postbronchiolitis rats had elevated pulmonary resistance and reduced forced-expiratory volume in 0.2 s. Most of the reduced forced-expiratory volume in 0.2 s was associated with reduced forced vital capacity, indicating premature airway closure as a prominent mechanism. The reduced airflow in postbronchiolitis rats was highly dependent on lung volume, being nearly normal at 70% lung capacity, but sevenfold less than normal at 30% lung capacity. Increased respiratory system hysteresis between functional reserve capacity and total lung capacity was evidence for increased airway closure at normal end-expiratory lung volumes in postbronchiolitis rats. We conclude that airway instability and closure is a prominent mechanism of the chronic airway dysfunction in rats that have recovered from viral bronchiolitis at an early age.
Department of Medicine, Morris Institute for Respiratory Research, School of Pharmacy, University of Wisconsin, Madison 53792, USA. rlsorkne@wisc.edu
Ronald L
RL
Sorkness
Amjad
A
Tuffaha
D000403:Airway Resistance / Q000502:physiology*; D000818:Animals; D029481:Bronchitis, Chronic / Q000503:physiopathology*; D005541:Forced Expiratory Volume / Q000502:physiology; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology; D051381:Rats; D011914:Rats, Inbred BN; D014109:Total Lung Capacity / Q000502:physiology