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

Abstract

We studied the effects of hypercapnia on the ventilatory response to nicotine in thirty anesthetized mongrel dogs. Ventilatory (V̇ E) and occlusion pressure (P 0.2) changes were assessed before and after intravenous injection of nicotine at concentrations of 1, 4, 16 and 64 μg/kg in four different groups of five dogs each. An end-tidal CO 2 ( Pet co2) was set at 40 mm Hg or 60 mm Hg by inspiration of 7% CO 2 in oxygen through a non-rebreathing valve. With Pet CO2 maintained at 40 mm Hg, P 0.2 had increased 1 min after nicotine injection from 1 to 16 μg/kg in a dose-dependent manner, and a subsequent decrease in P 0.2 below the initial value was observed at around 4 min. Injection of 64 μg/kg of nicotine produced a marked increase in P 0.2 and subsequent apnea. With Pet CO2 at 60 mm Hg, the time course of P 0.2 was qualitatively similar to that observed with Pet CO2 at 40 mm Hg, except that the change in P 0.2 was larger in the former case than in the latter, for a given nicotine dose. The ratio of the difference in maximal P 0.2 observed with Pet CO2 of 40 mm Hg and that at 60 mm Hg to the difference between Pet CO2 values ( ΔP O2/Δ Pet CO2 ) increased with nicotine dose from 1 to 4 μg/kg and, with a further increase in nicotine dose, the maximal Δ P 0.2/Δ Pet CO2 plateaued, while Δ P 0.2/Δ Pet CO2 obtained from the minimal P O2 values decreased in a nicotine dose-dependent fashion. These results suggest that hypercapnia enhances both stimulative and subsequent depressive ventilatory responses to nicotine.