Effects of neural drives on breathing in the awake state in humans

We have developed a mathematical model of the regulation of ventilation that successfully simulates breathing in the awake as well as in sleeping states. In previous models, which were used to simulate Cheyne-Stokes breathing and respiration during sleep, the controller was only responsive to chemical stimuli, and allowed no ventilation at sub-normal carbon dioxide levels. The current model includes several new features. The chemical controller responds continuously to changes in P-CO2 with a lower sensitivity during hypocapnia than in the hypercapnic ranges. Hypoxia interacts multiplicatively with P-CO2 over the entire range of activity. The controller in the current model, besides the chemical drive, includes also a neural component. This neural drive increases and decreases as the level of alertness chances, and adds or subtracts from ventilation levels demanded by the chemical controller. The model also includes the effects of post-stimulus potentiation (PSP) and hypoxic ventilatory depression (HVD). While PSP eliminates apneas after a disturbance and also dampens the subsequent dynamics of the respiration, it is not a major factor in the damping of the response. Another finding is that HVD is destabilizing. The model is the first to reproduce results reported in conscious humans after hyperventilation and after acute and longer-term hypoxia. It also reproduces the effects of NREM sleep. (C) 2002 Elsevier Science B.V. All rights reserved.