Multi-organ system model of O2 and CO2 transport during isocapnic and poikilocapnic hypoxia

A multi-organ systems model of O2 and CO2 transport is developed to analyze the control of ventilation and blood flow during hypoxia. Among the aspects of the control processes that this model addressed are possible mechanisms responsible for the second phase of the ventilatory hypoxic response to mild hypoxia, i.e., hypoxic ventilatory decline (HVD). Species mass transport processes are described by compartmental mass balances in brain, heart, skeletal muscle, and “other tissues” connected in parallel via the circulation. In pulmonary and systemic capillaries and in the vasculature connecting the systemic tissues, species transport processes are represented by a one-dimensional, convection-dispersion model. The effects of bicarbonate acid-base buffering, hemoglobin, and myoglobin on the transport processes are included. The model incorporates feedback control mechanisms through a cardiorespiratory control system in which peripheral and central chemoreceptors sense O2 and CO2 partial pressures. Model simulations of the ventilatory responses to isocapnic and poikilocapnic hypoxia show two phases with distinct dynamics. A fast phase is discernable immediately after switching from normoxic to hypoxic conditions, while a delayed slow phase (HVD) typically becomes manifested after several minutes. Model simulations allow quantitative evaluation of several proposed mechanisms to account for HVD. Under isocapnic hypoxia, simulations indicate that an increase in brain blood flow has no effect on HVD, but that HVD can be entirely described by central ventilatory depression (CVD). Under poikilocapnic hypoxia, the hypocapnia caused by hypoxic hyperventilation has no effect on HVD.