Carbon dioxide: A stronger driver of cardiac output than oxygen?

Dear Editor, The regulation of breathing by the gases oxygen (O2) and carbon dioxide (CO2) has since long been established, showing that CO2, to a much larger extent than O2, governs the respiratory effort. However, the effect of the same gases in the regulation of cardiac output (CO) has received limited scientific interest. Due to the fundamental importance of oxygen for the well-being of the organism, it has become accepted that it is O2 that mainly governs CO. However, extra-corporeal circulation experiments in animals, which can tightly and individually alter the levels of O2 and CO2 in the blood, have shown that increasing CO2 results in a substantial increase in CO, whereas a reduction of O2 will need to be pronounced to trigger a later and more moderate increase in CO (please confer with regulation of respiration). Further, for logistic reasons, it seems quite unlikely that respiration and circulation would be controlled by two different gas parameters (CO2—respiration; O2—circulation) since this would create great difficulty in achieving optimal ventilation/perfusion matching in the lung, which is a prerequisite for optimal gas exchange. Therefore, it would be more logical if both respiration and circulation were controlled by the same gas, that is, CO2. If accepting the above, then removal of CO2 is the fundamental gaseous driver of circulation and the resulting increased O2 uptake is a passive secondary phenomenon to the increased need to excrete CO2. The aim of this communication was to re-evaluate our previous animal data to potentially find further data in support of CO2 being the main gaseous driver of circulation, in the context of normal circulation.