title: Mechanism of the ventilatory response to carbon monoxide.
abstract: 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 nonperipheral chemoreceptor mechanisms. In each of six 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 less than 0.001) beginning 5-6 min after onset of 1% CO in O2 inhalation when COHb saturation reached 50-60%. In eight studies of six animals HCO3- concentration fell (from 21.3 to 15.8 meq/liter; P less than 0.001) and lactate concentration rose (from 2.5 to 4.2 meq/liter; P less than 0.05) in the cisternal cerebrospinal fluid during the CO-induced hyperpnea. Additional studies ruled out ventilatory stimulation from left heart failure or enhanced chemo-sensitivity 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 brain-cerebrospinal fluid acidosis; (c) mobilization of body CO2 stores due to the circulatory response to CO may obscure an initial depression of ventilation by CO.
mesh_terms: D000136:Acid-Base Equilibrium; D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D002248:Carbon Monoxide / Q000494:pharmacology*; D002263:Carboxyhemoglobin / Q000378:metabolism; D002302:Cardiac Output / Q000187:drug effects; D002490:Central Nervous System / Q000503:physiopathology; D002628:Chemoreceptor Cells; D006041:Goats; D000860:Hypoxia / Q000503:physiopathology; D007773:Lactates / Q000378:metabolism; D010101:Oxygen Consumption; D011433:Propranolol / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects*
chemical_list: D007773:Lactates; D002245:Carbon Dioxide; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin; D011433:Propranolol