The effects of topical and intravenous JM-1232(-) on cerebral pial microvessels of rabbits

BACKGROUND: JM-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 (CO(2)) reactivity is preserved. METHODS: Closed 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 CO(2) reactivity of cerebral pial vessels under JM-1232(-) (n = 6) or sevoflurane anesthesia (n = 6). RESULTS: Topical 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 CO(2) partial pressure. Slopes of linear regression and correlation coefficients in arterioles and venules were comparable for JM-1232(-) anesthesia and sevoflurane anesthesia. CONCLUSIONS: Topical 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 CO(2) responsiveness. At least from the perspective of vascular reactivity, JM-1232(-) thus appears safe for neurosurgical patients.