Mixed Venous CO2 and Ventilation During Exercise and CO2-Rebreathing in Humans

The physiological mechanism of exercise-induced hyperpnea is an important and long-standing issue in respiratory physiology research.1 However, the precise mechanism of exercise-induced hyperpnea still is not understood. It has been confirmed that neural central command from the hypothalamus plays an important role in respiratory control during exercise.2 Activation of receptors in working muscle3,4 and stimulation of the carotid body by elevated plasma potassium5 have both been shown to contribute to exercise-induced hyperpnea. However, most of the other hypotheses to explain exercise-induced hyperpnea have been based on the observed close relationship between ventilation and the level of metabolic work; these hypotheses include (1) sensing of CO2 by receptors in the pulmonary circulation,6, 7, 8, 9 (2) sensing of arterial CO2 partial pressure (PaCO2) as well as PaCO2 oscillation by the carotid body10,11 and (3) modulation of stretch-sensitive afferent activity by CO2.12,13 Thus, it has been widely assumed that metabolically produced CO2 is the most important element in the mechanism of exercise-induced hyperpnea. Therefore, the relationship between ventilation (Ve) and mixed venous CO2 partial pressure (PvCO2) as well as the relationship between Ve and PaCO2 needs to be fully analyzed in order to understand the contribution of metabolically produced CO2 to exercise-induced hyperpnea. However, most of the previous reports on PvCO2 dynamics during exercise in humans were not based on direct measurement, but rather on the estimation of PvCO2 by CO2 rebreathing,14,l5 and PvCO2 has been directly measured during exercise in humans only in a few studies.16 This is mainly because sampling of mixed venous blood during exercise in humans is technically difficult.