An integrated model of the human ventilatory control system: the response to hypercapnia

This work presents a mathematical model of the human respiratory control sy stem, based on physiological knowledge. it includes three compartments for gas storage and exchange (lungs, brain tissue and other body tissues), and various kinds of feedback mechanisms. These comprehend peripheral chemorece ptors in the carotid body, central chemoreceptors in the medulla and a cent ral ventilatory depression. The latter acts by reducing the response of the central neural system to the afferent peripheral chemoreceptor activity du ring prolonged hypoxia of the brain tissue. Furthermore, the model consider s local blood flow adjustments in response to O-2 and CO2 arterial pressure changes. II this study, the model has been validated by simulating the res ponse to square changes in alveolar PCO2, performed at different constant l evels of alveolar PO2. A good agreement with data reported in the literatur e has been checked. Subsequently, a sensitivity analysis on the role of the main feedback mechanisms on ventilation response to CO2 has been performed . The results suggest that the ventilatory response to CO2 challenges durin g hyperoxia can be almost completely ascribed to the central chemoreflex, w hile, during normoxia, the peripheral chemoreceptors provide a modest contr ibution too. By contrast, the response to hypercapnic stimuli during hypoxi a involves a complex superimposition among different factors with disparate dynamics. Hence, results suggest that the ventilatory response to hypercap nia during hypoxia is more complex than that provided by simple empirical m odels, and that discrimination between the central and peripheral component s based on time constants may be misleading.