The applicant proposes to examine the dissipative behavior of tissue structures during bronchoconstriction utilizing guinea pig models of allergic and exercise-induced asthma. By measuring pressure drop between alveolus and pleura, and airway opening and pleura, and calculating pressure-volume hysteresis areas, total lung resistance can be partitioned between airways (Raw) and tissue (TAR). The biochemical basis for changes in Raw and TAR will be examined using specific mediator inhibitors during allergen-induced constriction, and exercise-induced constriction, and by examining responses to exogenously administered bioactive molecules in intact animals and isolated lungs. Viscoelastic and viscoplastic behavior of TAR will be studied by considering step, and frequency responses to pressure-volume forcing. Tissue determinants of TAR will be studied by measuring length-tension characteristics of constricted and relaxed lung parenchymal strips following enzymatic digestion of elastin, collagen, and interstitial glycosaminoglycans. The functional role of contractile interstitial cells in determining TAR will be assessed by studying stress-strain behavior of parenchymal strips from bleomycin-exposed animals (which increases numbers of interstitial contractile cells). The contractile function of cultured guinea pig fibroblasts will be characterized as a potential model for studying cellular and molecular aspects relating to TAR.
