Carbon dioxide and venous return and their interaction as stimuli to ventilation in the cat.

1. Respiratory responses were measured in forty-seven cats, made decerebrate or anaesthetized with pentobarbitone or chloralose-urethane, to changes in the level of CO(2) infused into the inferior vena cava via an external oxygenator circuit or to changes in the volume of venous return or to the inhalation of CO(2).2. No consistent difference was found between the respiratory response to the increase in the level of CO(2) infused or CO(2) inhaled provided that the volume of venous return during both sets of tests was held constant at normal levels.3. If the volume of venous return was increased and the level of CO(2) infused maintained at levels such that V(CO2) did not increase, ventilation increased with a fall in P(a, CO2), a response lying approximately on the isometabolic curve.4. If the volume of venous return and the level of CO(2) infusion were raised together, a spectrum of intermediate respiratory responses was obtained which reproduced all those seen in earlier papers, in muscular exercise or other hypermetabolic states.5. None of the steady-state respiratory responses was significantly affected by bilateral vagotomy or section of the sinus nerves, though sinus nerve section slowed the responses to infused or inhaled CO(2) and they were then less precisely controlled.6. Additional experiments indicated that where CO(2) was infused or inhaled, the effective stimulus to respiration was an increase in mean P(a, CO2) in proportion to the CO(2) added and that the respiratory response to CO(2) was enhanced by reduced blood volume. How the changes in venous return were sensed and affected respiration, remains unclear.7. These results may explain why previous workers have obtained exaggerated respiratory responses to the infusion of CO(2) and why respiration increases rapidly at the start of exercise and is then maintained at high levels without discernible change in the chemical stimulus in arterial blood.