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

The mathematical model of the respiratory control system described in a pre vious companion paper is used to analyse the ventilatory response to hypoxi c stimuli. Simulation of long-lasting isocapnic hypoxia at normal alveolar PCO2 (40 mmHg = 5.33 kPa) shows the occurrence of a biphasic response, char acterized 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 ma inly ascribed to prolonged neural hypoxia. If isocapnic hypoxia is performe d during hypercapnia (PACO(2) = 48 mmHg = 6.4 kPa), the ventilatory respons e is stronger and HVD is minimal (about 1/10-1/5 of the initial peak). Duri ng poikilocapnic hypoxia, ventilation exhibits smaller changes compared wit h the isocapnic case, with a rapid return toward baseline within a few minu tes. Moreover, a significant undershoot occurs at the termination of the hy poxic period. This undershoot may lead to apnea and to a transient destabil ization of the control system if the peripheral chemoreflex gain and time d elay are twofold greater than basal.