Acute cardiovascular response to isocapnic hypoxia. II. Model validation

The role of the different mechanisms involved in the cardiovascular respons e to hypoxia [chemoreceptors, baroreceptors, lung stretch receptors, and ce ntral nervous system (CNS) hypoxic response] is analyzed in different physi ological conditions by means of a mathematical model. The results reveal th e following: 1) The model is able to reproduce the cardiovascular response to hypoxia very well between 100 and 28 mmHg PO2. 2) Sensitivity analysis o f the impact of each individual mechanism underlines the role of the barore flex in avoiding excessive derangement of systemic arterial pressure and ca rdiac output during severe hypoxia and suggests the existence of significan t redundancy among the other regulatory factors. 3) Simulation of chronic s inoaortic denervation (i.e., simultaneous exclusion of baroreceptors, chemo receptors, and lung stretch receptors) shows that the CNS hypoxic response alone is able to maintain quite normal cardiovascular adjustments to hypoxi a; however, suppression of the CNS hypoxic response, as might occur during anesthesia, led to a significant arterial hypotension. 4) Simulations of ex periments with controlled ventilation show a significant decrease in heart rate that can only partly be ascribed to inactivation of lung stretch recep tors. 5) Simulations performed by maintaining constant cardiac output sugge st that during severe hypoxia the chemoreflex can produce a significant dec rease in systemic blood volume. In all the previous cases, model prediction s exhibit a satisfactory agreement with physiological data.