Control of breathing: two types of delays studied in an integrated model of the respiratory system.

We use a recently developed mathematical model that integrates a reduced representation of the brainstem respiratory neural controller together with peripheral gas exchange and transport to study numerically the dynamic response of the respiratory system to several physiological stimuli. We compare between the system responses with two major sources of delay: circulatory transport vs. neural feedback dynamics, and we show that the dynamics of the neural feedback processes dictates the dynamic response to hypoxia and hypercapnia. The source of the circulatory delay (blood velocity vs. distance from the lungs to chemoreceptors) was found to be important. Our model predicts that periodic breathing is associated with the ventilatory "afterdischarge" (slow recovery of ventilation) after a brief perturbation of CO(2). We also predict that there could be two possible mechanisms for the appearance of periodic breathing and that circulatory delay is not a necessary condition for this to occur in certain cases. Copyright 2009 Elsevier B.V. All rights reserved.