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.
Sorkness
Ronald L
RL
Department of Medicine, Morris Institute for Respiratory Research, School of Pharmacy, University of Wisconsin, Madison 53792, USA. rlsorkne@wisc.edu
Tuffaha
Amjad
A
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