An integrated model of the human ventilatory control system: the response to hypoxia

Abstract

The mathematical model of the respiratory control system described in a previous companion paper is used to analyse the ventilatory response to hypoxic stimuli. Simulation of long-lasting isocapnic hypoxia at normal alveolar PCO2 (40 mmHg=5.33 kPa) shows the occurrence of a biphasic response, characterized by an initial peak and a subsequent hypoxic ventilatory decline (HVD). The latter is about as great as 2/3 of the initial peak and can be mainly ascribed to prolonged neural hypoxia. If isocapnic hypoxia is performed during hypercapnia (PACO2=48 mmHg =6.4 kPa), the ventilatory response is stronger and HVD is minimal (about 1/10-1/5 of the initial peak). During poikilocapnic hypoxia, ventilation exhibits smaller changes compared with the isocapnic case, with a rapid return toward baseline within a few minutes. Moreover, a significant undershoot occurs at the termination of the hypoxic period. This undershoot may lead to apnea and to a transient destabilization of the control system if the peripheral chemoreflex gain and time delay are twofold greater than basal.