ACETAZOLAMIDE ON THE VENTRAL MEDULLA OF THE CAT INCREASES PHRENIC OUTPUT AND DELAYS THE VENTILATORY RESPONSE TO CO2

1. Acetazolamide (0.1 mM) applied to the surface of the rostral ventrolateral medulla or microinjected beneath the medullary surface in chloralose-urethane-anaesthetized, vagotomized, carotid-denervated, paralysed, servo-ventilated cats produced a long-lasting increase in integrated phrenic nerve activity. 2. Extracellular pH measured beneath the rostral ventrolateral medulla exhibited a long-lasting decrease after surface acetazolamide but was not a good predictor, in each individual animal, of changes in phrenic activity. 3. Medullary carbonic anhydrase inhibition reduced the slope and the half-time of the phrenic response to rapid step CO2 increases. Conversely, acetazolamide did not affect the phrenic response to steady-state CO2 increases. 4. These data indicate that localized inhibition of medullary carbonic anhydrase causes a centrally mediated increase in ventilation that we attribute to medullary tissue hypercapnia and acidosis. In addition, these data indicate that medullary carbonic anhydrase may play a role in central CO2 chemotransduction.