Effect of hypercapnia on ventilatory response to intravenous nicotine administration in anesthetized dogs

We studied the effects of hypercapnia on the ventilatory response to nicotine in thirty anesthetized mongrel dogs. Ventilatory (VE) and occlusion pressure (P0.2) changes were assessed before and after intravenous injection of nicotine at concentrations of 1, 4, 16 and 64 micrograms/kg in four different groups of five dogs each. An end-tidal CO2 (PETCO2) was set at 40 mm Hg or 60 mm Hg by inspiration of 7% CO2 in oxygen through a non-rebreathing valve. With PETCO2 maintained at 40 mm Hg, P0.2 had increased 1 min after nicotine injection from 1 to 16 micrograms/kg in a dose-dependent manner, and a subsequent decrease in P0.2 below the initial value was observed at around 4 min. Injection of 64 micrograms/kg of nicotine produced a marked increase in P0.2 and subsequent apnea. With PETCO2 at 60 mm Hg, the time course of P0.2 was qualitatively similar to that observed with PETCO2 at 40 mm Hg, except that the change in P0.2 was larger in the former case than in the latter, for a given nicotine dose. The ratio of the difference in maximal P0.2 observed with PETCO2 of 40 mm Hg and that at 60 mm Hg to the difference between PETCO2 values (delta PO2/delta PETCO2) increased with nicotine dose from 1 to 4 micrograms/kg and, with a further increase in nicotine dose, the maximal delta P0.2/delta PETCO2 plateaued, while delta P0.2/delta PETCO2 obtained from the minimal PO2 values decreased in a nicotine dose-dependent fashion. These results suggest that hypercapnia enhances both stimulative and subsequent depressive ventilatory responses to nicotine.