When you hold your breath, which of the following stimulus would first lead to the urge to breathe?

A chemosensitive area is situated adjacent to the rhythm centre as well as the chemoreceptors associated with aortic arch and carotid artery are highly sensitive to CO2 and H+. Increase in CO2 and H+ signal the rhythm centre to make necessary adjustments in the respiratory process by which these substances can be eliminated. The role of oxygen in the regulation of respiratory rhythm is quite insignificant.