Effects of nitrous oxide on human regional cerebral blood flow and isolated pial arteries.

Background: Results from previous studies on the effect of nitrous oxide (N2O) on the cerebral circulation are conflicting. Early reports claim N2O to have no effect whereas recent findings demonstrate a cerebral cortical vasodilatation during N2O inhalation, but the regional cerebral blood flow (CBF) in the subcortical structures is unknown. Methods: Regional CBF was measured three-dimensionally with single photon emission computer-aided tomography after injection of xenon 133 in 8 spontaneously breathing men (mean age 29.6 yr) during normocapnia and hypocapnia with and without inhalation of 50% N2O. 8 isolated human pial arterial segments were mounted in organ baths. The segments were contracted with prostaglandin F-2 alpha and subjected to 30% oxygen and 5.6% carbon dioxide in nitrogen or N2O. Results: Normocapnic young men had a global CBF of 55 +/- 4 ml . 100 g(-1) . min(-1). Decreasing end-tidal CO2 tension by 1.3 kPa (9.3 mmHg) reduced CBF uniformly, with a decrease in global CBF to 45 +/- 2 ml . 100 g(-1) . min(-1) (P < 0.0001). During normocapnia, inhalation of 50% N2O increased mean CBF to 67 +/- 7 ml . 100 g(-1) . min(-1) (P < 0.0001). Inhalation of 5096 N2O during hypocapnia increased mean CBF to 63 +/- 5 ml . 100 g(-1) . min(-1) (P < 0.0001). During N2O inhalation there was no significant difference in mean CBF between normo- and hypocapnia. However, during hypocapnia, but not during normocapnia, N2O inhalation significantly changed the distribution of regional CBF (P < 0.0001). Compared with hypocapnia without N2O, flow increased through the frontal (143%), parietal (140%) and temporal (133%) regions as well as through insula (151%), basal ganglia (145%) and thalamus (133%). In isolated human pial arteries, addition of N2O changed neither basal tension, nor the contraction elicited by prostaglandin F-2 alpha. Conclusions: Inhalation of 50% N2O increased global CBF mainly by augmenting flow in frontal brain structures. In contrast, changes in carbon dioxide without N2O affected CBF uniformly in the brain. The uneven change in distribution of the CBF when N2O was added during hypocapnia, the reduced carbon dioxide response, and the lack of effect of N2O on isolated human pial arteries suggest that N2O may increase metabolism in selected brain areas.