Abstract
BackgroundJM-1232(-) is a novel anesthetic agent which acts through gamma-aminobutyric acid receptors. Cerebral pial vascular effects of JM-1232(-) are unknown. We thus evaluated topical and intravenous effects of JM-1232(-) on cerebral pial microvessels in rabbits, and the extent to which carbon dioxide (CO2) reactivity is preserved.MethodsClosed cranial windows were used to visualize cerebral pial circulation in 29 Japanese white rabbits. In the first experiment, the cranial window was superfused with increasing concentrations of JM-1232(-): 10-11, 10-9, 10-7, 10-5 mol/L, n = 8 per concentration. In the second experiment, we examined the effects of an intravenous bolus of 1 mg/kg bolus of JM-1232(-), followed by the continuous infusion at 0.3 mg/kg/minute on cerebral pial vascular alteration (n = 9). In the third, we examined CO2 reactivity of cerebral pial vessels under JM-1232(-) (n = 6) or sevoflurane anesthesia (n = 6).ResultsTopical application of JM-1232(-) did not change pial venular diameter, and constricted arterials only at the highest concentration. Intravenous administration of JM-1232(-) produced cerebral pial constriction which gradually diminished over time. Under intravenous administration of JM-1232(-) and inhaled sevoflurane, diameters of vessels increased in parallel with CO2 partial pressure. Slopes of linear regression and correlation coefficients in arterioles and venules were comparable for JM-1232(-) anesthesia and sevoflurane anesthesia.ConclusionsTopical application of JM-1232(-) had little effect on cerebral pial vessels. Intravenous administration produced vasoconstriction of cerebral pial arterioles and venules, however those changes were clinically unimportant. In addition, JM-1232(-) did not impair CO2 responsiveness. At least from the perspective of vascular reactivity, JM-1232(-) thus appears safe for neurosurgical patients.
Highlights
JM-1232(-) is a novel anesthetic agent which acts through gamma-aminobutyric acid receptors
We evaluated the effect of JM-1232(-) on carbon dioxide (CO2) reactivity of cerebral pial vessels
The window was flushed with artificial cerebrospinal fluid (aCSF) for 30 minutes before administration of the concentration, and the superfusion rate was set at 30 mL/h, In the second set of experiment (n = 9), we examined the effects of intravenous administration of JM-1232(-) on cerebral pial vasculature
Summary
The Ethics Committee on Animal Research, University of Yamanashi, Yamanashi, Japan, approved this study. Control values for cerebral pial arteriolar and venular diameters and various laboratory data including MAP, heart rate (HR), rectal temperature, arterial blood gas tensions and pH, plasma electrolytes, glucose and lactate concentration were recorded. The window was flushed with aCSF for 30 minutes before administration of the concentration, and the superfusion rate was set at 30 mL/h, In the second set of experiment (n = 9), we examined the effects of intravenous administration of JM-1232(-) on cerebral pial vasculature. MAP, HR, rectal temperature, arterial blood pH, PaCO2, arterial oxygen tension (PaO2), and plasma concentrations of Na+, K+, glucose and lactate in each experimental group, topical concentration-dependent effects of JM-1232(-), and CO2 responses of cerebral pial vessels were compared using analysis of variance (ANOVA) and post hoc Tukey tests. Values are represented as means ± SDs; A P value less than 0.05 was considered statistically significant
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