Mucosal Folding and Airway Smooth Muscle Shortening

smooth muscle are given by the intercept of each curve on the abscissa. At equilibrium, the smooth muscle tension is exactly equal and opposite to the load. The tension length curves shown in Figure 1 give the load acting on smooth muscle including both the load imposed by the airway wall and that imposed by airway parenchymal interdependence. The curves reveal how this load changes as a function of smooth muscle shortening and as a function of lung distending pressure or lung volume. The tension smooth muscle must develop and the load it acts against to produce a given degree of smooth muscle shortening is: l. Highly curvilinear; particularly at high PL; 2. Decreases by an order of magnitude from PL=20 em HzO to PL=2 em H zO; 3. Is shaped differently depending on the initial PL. Starting at any given PL, smooth muscle tension can increase and shortening can occur along the pathway illustrated in Figure 1 for the appropriate value of PL. Tension can continue to increase, shortening progress until the muscle develops the maxim urn tension it is capable of. This is determined by the point of intersection of a load length curve with the appropriate maximal active force-length curve for the smooth muscle in the airway wall. The dashed lines in Figure 1 are two theoretical maximum length tension curves assuming that !max, the length for maximum active tension is at a l/ lo=0.78; ie, at a lung volume equivalent to FRC. The upper curve is for a smooth muscle layer thickness of 20 J.L and the lower for a thickness of 10 J.L. The points of intersection of the load (tension) length curves with the maximum length tension curves indicate the maximum degree of airway narrowing that can occur. These points are assumed by many to be the determinants of the plateau on the dose-response curve. For large loads, the amount of smooth muscle is an important determinant of the degree of airway narrowing. For smaller loads such as PL=5 em H 20 or 2 em H 20 , the degree of narrowing is largely independent of the thickness of the smooth muscle layer (37 % and 41 % shortening for an initial PL=5 em H 20 for smooth muscle thickness 10 ll and 20 J.L, respectively; 32% and 33% for an initial PL=2 em HzO, respectively). This analysis suggests that for the particular airway studied, when loads are small relative to the appropriate maximum length-tension curve, the amount of smooth muscle is relatively unimportant. It becomes important when the loads are large. In normal subjects when PL is decreased from 5 to 2 em HzO , the plateau on the dose response curve is abolished, and bronchoconstriction becomes unlimited. 3 A decrease in lung recoil is the only experimental intervention to date which abolishes the plateau. We suggest that an inflammatory exudate external to the smooth muscle layer would act in a similar way to loss of recoil as it would allow the airway to recoil inward and narrow while making Ppb less negative and decreasing the local value of 1-L· Increasing smooth muscle contractility, and increasing mucosal and submucosal thickness and luminal exudate would all make the situation worse. The mechanism for the absence of a plateau in asthma may be identical to the mechanism of plateau abolition in normal subjects breathing at low lung volum es, namely a decrease in load. 88S

REFERENCES

Martin HB, Proctor DF. Pressure-volume measurements in dog bronchi. J Appl Physioll958; 13:337-43 2 Lai-Fook SJ. A continuum mechanics analysis of pulmonary vascular interdependence in isolated dog lobes. J Appl Physiol 1979; 46:419-29 3 Ding DJ, Martin JG, Macklem PT. Effects of lung on maximal methacholine-induced bronchoconstriction in normal humans. J Appl Physiol 1987; 62:1324-30

Mucosal Folding and Airway Smooth Muscle Shortening* Mitsushi Okazawa, MD; Lu Wang, MD; Rodne y K. Lambert, PhD; Lorraine Verburgt, BSc; Sverre Veda/, MD; joel L. Bert, PhD; Kenneth L. Pinder, PhD; and Peter D. Pare, MD

is marked heterogeneity of airway narrowing and T here airway smooth muscle (ASM) shortening in response

to bronchoconstricting stimuli. It was hypothesized that folding of the mucosa during bronchoconstriction could provide a significant load to the ASM and thus contribute to the variation in shortening. It was further hypothesized that the bronchoconstriction would be less in airways with a thicker submucosal layer. To test these hypotheses, morphometric measurements were used to calculate airway smooth muscle shortening in excised dog lung lobes after administration of maximal constricting concentrations of carbachol aerosol, and the elastic modulus of rabbit tracheal mucosal membrane was measured. Morphometric analyses show that the thickness of the mucosal membrane was an important predictor of ASM shortening in similar sized airways. We assumed that the elastic modulus of the mucosal membrane in the intraparenchymal airways would be similar to that in the trachea. Based on this assumption, the number of folds and the elastic modulus of the tracheal mucosal membrane were used to calculate the force necessary to deform the mucosal membrane during smooth muscle contraction using the equation of Lambert. 1 The results show that the load applied to the smooth muscle by mucosal folding was substantial, and at transpulmonary pressure of 5 em H 20 was -80% of that provided by distortion of the lung parenchyma. These data support the hypothesis that mucosal folding is a determinant of ASM shortening and also support the hypothesis that the limited narrowing seen in airways with thicker mucosal membrane can be explained on the basis of an increased load. If the mechanical properties of the thickened mucosal membrane remain the same in asthma and COPD, these data suggest that the mucosal thickening seen in these conditions may help to attenuate excessive airway narrowing. REFEREN CE

l L ambert RK. Role of bronchial basement membrane in airway collapse. J Appl Physiol1991 ;7l:666-73 *From the University of British Columbia, Pulmonary Research Laboratory and Department of Chemical Engineering, Vancouver, BC, Canada. Reprint requests: Dr. Okazawa, Pulmonary Research Lab, St . Paul's Hospital, 1081 Burrard St, Vancouver, BC, V6Z 1¥6, Canada 37th Annual Aspen Lung Conference