Effect of Propofol on Carotid Body Chemosensitivity and Cholinergic Chemotransduction

Abstract

Propofol decreases the acute hypoxic ventilatory response in humans and depresses in vivo carotid body chemosensitivity. The mechanisms behind this impaired oxygen sensing and signaling are not understood. Cholinergic transmission is involved in oxygen signaling, and because general anesthetics such as propofol have affinity to neuronal nicotinic acetylcholine receptors, the authors hypothesized that propofol depresses carotid body chemosensitivity and cholinergic signaling. An isolated rabbit carotid body preparation was used. Chemoreceptor activity was recorded from the whole carotid sinus nerve. The effect of propofol on carotid body chemosensitivity was tested at three different degrees of PO2 reduction. Nicotine-induced chemoreceptor response was evaluated using bolus doses of nicotine given before and after propofol 10-500 microM. The contribution of the gamma-aminobutyric acid A receptor complex was tested by addition of gamma-aminobutyric acid A receptor antagonists. Propofol reduced carotid body chemosensitivity; the magnitude of depression was dependent on the reduction in PO2. Furthermore, propofol caused a concentration-dependent (10-500 microM) depression of nicotine-induced chemoreceptor response, with a 50% inhibitory concentration (propofol) of 40 microM. Bicuculline in combination with propofol did not have any additional effect, whereas addition of picrotoxin gave a slightly more pronounced inhibition. It is concluded that propofol impairs carotid body chemosensitivity, the magnitude of depression being dependent on the severity of PO2 reduction, and that propofol causes a concentration-dependent block of cholinergic chemotransduction via the carotid sinus nerve, whereas it seems unlikely that an activation of the gamma-aminobutyric acid A receptor complex is involved in this interaction.