The current study aims to investigate the relative contributions of each of the processes that govern airway smooth muscle mechanical behaviour. Studies have shown that breathing dynamics have a substantial effect on airway constriction in healthy and diseased subjects, yet little is known about the dynamic response of the main instigator of airway constriction, Airway Smooth Muscle (ASM). In this work several models are developed to further the understanding of ASM dynamics, particularly the roles and interactions of the three dominant processes in the muscle: contractile dynamics, length adaptation and passive dynamics. Three individual models have been developed, each describing a distinct process or structure within the muscle. The first is a contractile model which describes the contractile process and the influence of external excitation on contractile behaviour. The second model incorporates the contractile model to describe length adaptation, which includes the reorganisation and polymerisation of contractile elements in response to length changes. The third model describes the passive behaviour of the muscle, which entails the mechanical behaviour of all non-contractile components and processes. As little data on the passive dynamics of the muscle was available in the literature, a number of experiments were conducted to investigate relaxed ASM dynamics. The experimental data and mathematical modelling showed that passive dynamics plays not only a dominant role in relaxed ASM, but contributes considerably to the dynamics of contracted muscle as well. A novel theory of sequential multiplication in passive ASM is proposed and implemented in a mathematical model. Experiments and literature validated the model simulations. Further integration of the models and improved force control modelling of length adaptation is proposed for future study. It is likely that the coupling of the models presented here with models describing other airway wall components will provide a more complete picture of airway dynamics, which will be invaluable for understanding respiratory disease.

The main goal of this research was the in vitro investigation of the stiffness response of contracted airway smooth muscles under different external oscillations. Living animal airway smooth muscle tissues were dissected from pig tracheas and stimulated by a chemical stimulus (acetylcholine). These tissues were then systematically excited with different external vibrations. The force change was recorded to reflect the muscle stiffness change under vibration. The static and dynamic stiffness of contracted airway smooth muscles in isometric contraction were determined before, during and after vibrations. A continuum cross-bridge dynamic model (the fading memory model) was modified to accommodate smooth muscle behaviour and dynamically describes the cross-bridge kinetics. A two-dimensional finite element model (FEM) was developed to simulate longitudinal and transverse vibrations of the tissue. An empirical equation, derived from the experiments, is incorporated into the FEM. The results indicate that the stiffness of active smooth muscles can be physically reduced using external vibrations. This reduction is caused by a certain physical position change between actin and myosin. The dynamic stiffness has the tendency of decreasing as the frequency and/or amplitude of external vibration increases. However, the static stiffness decreases with an increase in the frequency and amplitude of excitation until it reaches a critical value of frequency where no variation in stiffness is observed. It is postulated that the tissue elasticity and mass inertia are the main contributors to the dynamic stiffness while the actin-myosin cross-bridge cycling is the main contributor to the static stiffness.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Linköping : Univ., 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Dissertation (Ph.D.)--University of South Florida, 2007. / Includes vita. Includes bibliographical references (leaves 180-204). Also available online.

Thesis (Ph. D.)--University of Oklahoma. / Bibliography: leaves 153-217.