Airway and tissue behavior during induced constriction in rats: intravenous vs. aerosol administration.

The distribution of contractile agonist during intravenous (i.v.) or aerosol (AR) administration is likely to be different. We questioned whether the different pattern of distribution would result in different effects on lung tissue response. We measured tracheal and alveolar pressure in open-chest mechanically ventilated [frequency 1 Hz, tidal volume 8 ml/kg, positive end-expiratory pressure (PEEP) 3 cmH2O] rats under control conditions and after i.v. or AR administration of saline or methacholine (MCh; i.v., 50 micrograms.kg-1.min-1; AR, 256 mg/ml). We calculated lung elastance and resistances of lung, tissue, and airway by fitting the equation of motion to changes in tracheal and alveolar pressure. Lungs were then frozen in situ with liquid nitrogen (PEEP=3 cmH2O) and processed via freeze substitution. Airway constriction was assessed by measuring the ratio of airway lumen to ideally relaxed area. Tissue distortion was assessed by measuring mean linear intercept between alveolar walls (Lm), atelectasis index (ATI) derived by calculating ratio of tissue to air space, and SD of Lm and ATI. I.v. and AR MCh increased lung resistance to a similar degree. However, changes in tissue resistance and lung elastance after AR MCh were significantly greater than those after i.v. MCh, whereas the change in airway resistance was significantly less. After i.v. MCh, airway constriction was prominent and evenly distributed. After AR MCh, airway constriction was less prominent and decreased as airway size decreased. Tissue distortion, i.e., SD of Lm and ATI, was significantly greater after AR than i.v. MCh.(ABSTRACT TRUNCATED AT 250 WORDS)