Non-invasive tracking of peripheral ventilatory response to carbon dioxide

We propose a new method for quantifying the ventilatory sensitivity of the peripheral chemoreceptors to changes in CO2 through analysis of the natural breath-to-breath variations in ventilation (y) and alveolar PCO2 (x). This technique is truly non-invasive in that the need for administering CO2-enriched mixtures is circumvented, and peripheral chemosensitivity is assessed while the respiratory control system operates in its normal eucapnic state, unperturbed by external interventions. The method is based on solution of the inverse problem relating the cross-correlation between alveolar PCO2 and ventilation changes, and the autocorrelation of changes in alveolar PCO2. Tests are performed using simulated data generated by a closed-loop respiratory control model. The impulse response of the controller and the convective delay between lungs and chemoreceptors are estimated from the data. Subsequently, the best exponential fit to the estimated impulse response yields values for the effective controller gain (G) and the associated time constant of the response. The estimates of G contain a small contribution from the control chemoreflex gain; however, the relation between changes in G and changes in peripheral gain remains unaltered. The effects of other details in the computation procedure, such as length of data sequence, maximum number of correlation lags and starting lag number, are also investigated.