Short-lived isotopes in central chemical control of ventilation

Central chemical ventilatory drive is dependent on electrolyte and acid-base status of brain ECF, as well as the interaction between H+ metabolism and CO2 fixation and metabolism of amino acid neurotransmitters-GABA and glutamate. In the anesthetized dogs, using the short-lived positron emitting isotope of carbon (11C) either in the form of molecular CO2 or as HCO3- injected intraarterially it was demonstrated that there is first pass uptake of 16% of HCO3- from blood into brain and 86% uptake of molecular CO2, thus indicating that the brain-blood barrier is permeable to HCO3-, but that HCO3- content in the CNS is regulated as a function of dissociation of strong ions such as Cl- and Na+. Relationship between CO2 fixation and brain glutamine was studied with intraarterial injection of 13N-ammonia and its turnover into glutamine when PCO2 was increased. Ammonia turnover into glutamine was increased by a factor of 2 when PaCO2 was increased by 35 torr, and this rise in glutamine was linearly related to the rise in CSF [HCO3-]. Glutamine is then converted into the active neurotransmitters GABA and glutamate. Thus, the short-lived isotopes allow for assessment of the interaction of biochemical events in the CNS in the central respiratory drive.