Identification of Closed-Loop Chemoreflex Dynamics Using Pseudorandom Stimuli

A brief disturbance to respiratory chemical feedback loops may initiate an interval of oscillatory fluctuations in ventilation1. The propensity for such oscillations to occur often is quantified1, 2 in terms of chemical feedback “loop gain”. A more direct and more complete characterization of the stability of ventilation can be obtained, however, by measuring the time course of the ventilatory response to a standard, brief disturbance3, 4. With appropriate parameterization of such responses, one can obtain indices which are highly correlated with loop gain, or can calculate loop gain itself. To characterize and compare the dynamics of central and peripheral chemoreflex loops of mail to disturbances, we have assessed the closed-loop ventilatory responses to single-breath inhalations of hypercapnic and hypoxic gases respectively. Such assessments in awake man are hampered by the typically large ventilatory variability relative to the small ventilatory responses elicited by such brief chemical stimuli. To overcome this limitation we have used pseudorandom chemical stimulation instead of single-breath inhalations. The responses were parameterized using the prediction-error method of transfer function estimation5.