AIRWAY SMOOTH-MUSCLE SHORTENING IN EXCISED CANINE LUNG LOBES

To estimate the importance of lung parenchymal airway interdependence in attenuating airway narrowing, airway smooth muscle shortening in response to nebulized carbachol was measured in excised canine lung lobes and compared with the calculated load applied by tung elastic recoil. Pulmonary resistance of matched right and left upper lobes of five dogs was measured in a pressure-compensated volume plethysmograph by forced oscillation (6 Hz) before and after administration of an aerosol of carbachol (2.50 mg/ml) or saline. Matched lobes were studied at transpulmonary pressures (PL) Of 5, 7, 10, 12, and 15 cmH2O. The lungs were then fixed at that PL by pulmonary arterial perfusion with formaldehyde, and cross sections of multiple airways from each lobe (n = 275) were examined by use of morphometric techniques to measure luminal area and smooth muscle length. By use of the saline lobe as a control, percentage of muscle shortening and decrease in airway lumen area caused by carbachol could be calculated. Passive and active smooth muscle stresses in each airway were calculated from PL and the calculated change in peribronchial pressure for a given change in airway diameter. The increase in pulmonary resistance and average smooth muscle shortening after administration of carbachol was greater in lobes held at lower PL. There was marked variation in narrowing between airways within a lobe: smooth muscle shortening ranged between 0 and 65% but averaged <45% at all levels Of PL. Active stress increased with increasing PL: average stress at PL levels of 5 and 7 cmH2O were 168 +/- 18 and 10.5 +/- 16 g/cm2, respectively, whereas at, 12 and 15 cmH2O values were 602 +/- 92 and 517 +/- 62 g/cm2, respectively. These values were less than those predicted from published data relating maximal airway smooth muscle stress to length. These results show that in situ airway smooth muscle contraction is opposed by substantial elastic loads. However, the load applied by lung elastic recoil is probably not the only contributor to the generation of active wall stress and cannot entirely explain submaximal smooth muscle shortening.