title: The effects of topical and intravenous JM-1232(-) on cerebral pial microvessels of rabbits.
abstract: 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 (CO2) 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 CO2 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 CO2 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 CO2 responsiveness. At least from the perspective of vascular reactivity, JM-1232(-) thus appears safe for neurosurgical patients.
authors: Department of Anesthesiology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo Yamanashi, 409-3898 Japan.
authors: Kodai
authors: K
authors: Ikemoto
authors: Surgical Center, University of Yamanashi Hospital, University of Yamanashi, 1110 Shimokato, Chuo Yamanashi, 409-3898 Japan.
authors: Tadahiko
authors: T
authors: Ishiyama
authors: Department of Anesthesiology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo Yamanashi, 409-3898 Japan.
authors: Noriyuki
authors: N
authors: Shintani
authors: Department of Anesthesiology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo Yamanashi, 409-3898 Japan.
authors: Nobumasa
authors: N
authors: Asano
authors: Department of Outcomes Research, The Cleveland Clinic, Ohio, USA.
authors: Daniel I
authors: DI
authors: Sessler
authors: Department of Anesthesiology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo Yamanashi, 409-3898 Japan.
authors: Takashi
authors: T
authors: Matsukawa
mesh_terms: D061605:Administration, Intravenous; D000287:Administration, Topical; D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006935:Hypercapnia / Q000503:physiopathology; D016857:Hypocapnia / Q000503:physiopathology; D054833:Isoindoles / Q000008:administration & dosage* / Q000494:pharmacology*; D010841:Pia Mater / Q000098:blood supply* / Q000187:drug effects*; D010879:Piperazines / Q000008:administration & dosage* / Q000494:pharmacology*; D011817:Rabbits; D014699:Venules / Q000187:drug effects* / Q000502:physiology
chemical_list: C534223:3-(2-(4-methyl-1-piperazinyl)-2-oxoethyl)-2-phenyl-3,5,6,7-tetrahydrocyclopenta(f)isoindol-1(2H)-one; D054833:Isoindoles; D010879:Piperazines
keywords: Anesthesia; Cerebral microcirculation; Cranial window; JM-1232(-); Sevoflurane