Abstract
The use of physiologically-based computational models of chemoreflex control of ventilation has provided general insights into the roles of specific mechanisms in the genesis of periodic breathing and apneas. Our early studies utilized formal mathematical approaches to simplify complex models of this type so that their behaviors could more easily be predicted from various combinations of physiological and environmental parameters. Because it is difficult to apply such models to individual patients, we subsequently pursued a “black-box” approach in which the objective was to characterize the dynamic properties of the system for individual subjects, then relate these properties to physiological and environmental parameters. By stimulating ventilation through pseudorandom variations in inspired { CO}2 (or { O}2) level, we estimated input–output models, both open-loop (i.e., from end-tidal \({P}_{\mathrm{C{O}_{2}}}\) to ventilation) and closed-loop (i.e., from inspired { CO}2 to ventilation). We found that the dynamic properties of the resulting models differ between normal subjects and both sleep apnea patients and heart failure patients. We also demonstrated in normal subjects that the closed-loop model does not change between wakefulness and quiet sleep, even though the gain of the open-loop (or controller) model decreases. To explore the mechanistic basis for these findings using a detailed, physiologically-based, chemoreflex model, we enhanced the typical model of this type by improving the representation of { O}2 transport and distribution beyond the usual, single lumped-compartment, approach. In our new model, brain and muscle tissue each comprise two subcompartments with intercompartmental diffusion and arterio-venous shunting, as well as { O}2 binding to myoglobin in muscle. We use this model to predict changes in brain tissue \({P}_{\mathrm{{O}_{2}}}\) during sleep apnea. Chapter 8 provides another approach to respiratory control system modeling while Chap. 6 discusses the role of transport delay in respiratory control.
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This work was supported by grants OH008651 from NIOSH and NS050289 from NIH.
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Bruce, E.N. (2013). Experimental Studies of Respiration and Apnea. In: Batzel, J., Bachar, M., Kappel, F. (eds) Mathematical Modeling and Validation in Physiology. Lecture Notes in Mathematics(), vol 2064. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-32882-4_7
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