Translational Research: Multi-Scale Models of the Pulmonary Circulation in Health and Disease
The pulmonary circulation is a unique low resistance system that carries almost the entire cardiac output, and is responsible for the essential role of providing oxygenated blood to the body. As the pulmonary circulation differs from the systemic circulat
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Abstract The pulmonary circulation is a unique low resistance system that carries almost the entire cardiac output, and is responsible for the essential role of providing oxygenated blood to the body. As the pulmonary circulation differs from the systemic circulation in its development, structure, and function, it is often most appropriate to study the mechanisms that contribute toward pulmonary vascular disease separately from those of systemic vascular disease at the genetic, cellular, tissue and organ level. Here we review the development of multi-scale, anatomically based models of the pulmonary circulation. These models aim to describe the interaction of structural and functional aspects of the pulmonary circulation that are the most important in determining the effective uptake of oxygen to the blood. We describe how these models have been used to understand normal lung physiology and to explain outcomes in pulmonary disease. Finally, we consider the future of multi-scale modeling in the pulmonary circulation and discuss what can be learned from well-developed multi-scale models of the pulmonary airspaces that interact closely with the lung’s circulatory system.
1 Introduction Experimental or imaging studies of the pulmonary system are fraught with difficulties due to the nature of the lung’s structure and function. The lung comprises trees of airways and blood vessels that are ‘suspended’ within an extremely A. R. Clark (&) M. H. Tawhai Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand e-mail: [email protected] K. S. Burrowes Department of Computer Science, The University of Oxford, Oxford, UK
Stud Mechanobiol Tissue Eng Biomater (2013) 14: 259–286 DOI: 10.1007/8415_2012_152 Ó Springer-Verlag Berlin Heidelberg 2012 Published Online: 15 September 2012
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delicate parenchymal tissue [1]. The in vivo lung is maintained in contact with the wall of the thoracic cavity by negative pressure in the intrapleural ‘space’ [2]. Ex vivo experimentation with lung tissue is difficult to reconcile with in vivo behavior as when removed from the body the lung recoils to considerably smaller volumes than are encountered in breathing, and the lung changes in shape. The advent of modern imaging has provided opportunity to study the lung in situ, however this is again complicated by lung deformability and its air content. In awake humans the lung is typically functioning in an upright posture, and because the delicate tissue is readily deformable there is a substantial gradient of tissue density along the cranial-caudal axis [3]. Magnetic resonance imaging (MRI) and computed tomography (CT) are currently constrained to horizontal postures, i.e. supine or prone. The lungs are typically at a smaller volume in these postures than when upright [4], and the density gradient is in a different axis. This impacts on regional lung expansion [5], pulmonary blood volume and flow distribution [6], the rela_ [6], and so gas exchange _ and perfusion (Q) tionship between ve
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