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Hypoxia induces unstable breathing such as Cheyne-Stokes breathing primarily through the increase in the peripheral chemoreceptor gain to CO2. Another consequence of hypoxia may be the direct depression of the respiratory center known as hypoxic ventilatory depression (HVD). The present study was undertaken to predict the effect of HVD on the generation of unstable breathing during hypoxia by way of a computer simulation. To represent HVD, the present respiratory control model includes the control of cerebral blood flow and a mechanism which reduces ventilation in proportion to the brain tissue PO2. Analyses conducted both in the frequency domain and the time domain demonstrated that incorporating the HVD mechanisms into the model considerably increased the open-loop gain and thereby destabilized the respiratory control system. Increase in the peripheral CO2 gain due to relative hypoxia (caused by ventilatory depression) accounted for only half of the increase in the overall loop gain found in the presence of HVD. Considerable portion of the increase in the open-loop gain could be explained by the relative hypercapnia due to ventilatory depression.

Destabilization of the Respiratory Control by Hypoxic Ventilatory Depressions: A Model Analysis.