Mechanism of the ventilatory response to carbon monoxide

The effects of carbon monoxide on ventilation were studied in unanesthetized goats. Responses to single breaths of 10-25% CO in O₂, which rapidly raised carboxyhemoglobin (COHb) from 5 to 60%, were considered to reflect peripheral chemoreceptor mediated reflexes whereas responses to continuous inhalation of 1% CO in O₂, which slowly raised COHb from 0 to 60%, were considered to reflect both peripheral chemoreceptor and non peripheral chemoreceptor mechanisms. In each of 6 goats, single breaths of CO failed to elicit any immediate ventilatory response. However, slow buildup of carboxyhemoglobinemia in the same animals always elicited ventilatory stimulation (from a mean of 7.43 to 16.02 liter/min, P<0.001) beginning 5-6 min after onset of 1% CO in O₂ inhalation when COHb saturation reached 50-60%. In 8 studies of 6 animals HCO₃^- concentration fell (from 21.3 to 15.8 meq/liter; P<0.001) and lactate concentration rose (from 2.5 to 4.2 meq/liter; P<0.05) in the cisternal cerebrospinal fluid during the CO induced hyperpnea. Additional studies ruled out ventilatory stimulation from left heart failure or enhanced chemosensitivity to carbon dioxide. Although the delayed hyperpnea was associated with a hyperdynamic cardiovascular response to CO, blockade of these circulatory effects with propranolol (2 mg/kg) failed to abolish the delayed hyperpnea; however, the propranolol did unmask an element of ventilatory depression which preceded the hyperpnea. Conclusions were: (a) hyperventilation in response to CO inhalation is not mediated by the carotid bodies; (b) the delayed hyperpnea in response to CO inhalation is primarily due to braincerebrospinal fluid acidosis; (c) mobilization of body CO₂ stores due to the circulatory response to CO may obscure an initial depression of ventilation by CO.