Halothane decreases the rate of production of cerebrospinal fluid. Possible role of vasopressin V1 receptors.

Abstract

Circulating vasoactive hormones (e.g., vasopressin) play an important role in the regulation of blood flow to the choroid plexus and the rate of cerebrospinal fluid (CSF) production. We tested the hypothesis that halothane decreases CSF production through a vasopressin-related mechanism and examined the related changes in blood flow to the choroid plexus. Using ventriculocisternal perfusion, CSF production was measured in chloralose anesthetized, normothermic rabbits whose lungs were mechanically ventilated. Rabbits received either 0.5 minimum alveolar concentration (MAC; end-tidal) of halothane (added to a preestablished chloralose anesthetic), 0.5 MAC of halothane in the presence of a vasopressin V1 antagonist (iv), or the V1 antagonist alone. In addition, we examined animals in which no intervention was made (time control) and animals subjected to a 25% decrease in mean blood pressure produced by hemorrhage, with and without the V1-antagonist. In a separate series of rabbits, regional and total blood flows to the brain and the choroid plexus were measured using radioactive microspheres. These studies were carried out under similar conditions, except that the effects of end-tidal 0.25, 0.5, and 1 MAC of halothane were examined in each rabbit (each added to a preestablished chloralose anesthetic). Under control conditions, blood flow to the choroid plexus averaged 351 +/- 198 ml.min-1.100 g-1 (mean +/- SD) and CSF production averaged 10.1 +/- 1.9 microliters.min.-1. Halothane (0.25, 0.5, and 1 MAC) did not alter choroid plexus blood flow but decreased CSF production by 28 +/- 6% at 0.5 MAC (P < .05). In contrast, 1 MAC of halothane increased total blood flow to the brain by 20 +/- 25% (P < .05). The V1 antagonist, which did not affect production of CSF when given alone, prevented the decrease in CSF production in response to halothane. Hemorrhage decreased blood flow to the choroid plexus but not to the brain, and the V1 antagonist attenuated the decrease in the rate of CSF production by hemorrhage (34 +/- 11% vs. 48 +/- 18%, P < .05). Halothane decreases CSF production with no net change in the blood flow to the choroid plexus. Decrease in CSF production appears to be mediated through a vasopressin-related mechanism and not to the blood pressure decrease seen during halothane anesthesia.