title: The effects of Y-27632 on pial microvessels during global brain ischemia and reperfusion in rabbits.
abstract: Global brain ischemia-reperfusion during propofol anesthesia provokes persistent cerebral pial constriction. Constriction is likely mediated by Rho-kinase. Cerebral vasoconstriction possibly exacerbates ischemic brain injury. Because Y-27632 is a potent Rho-kinase inhibitor, it should be necessary to evaluate its effects on cerebral pial vessels during ischemia-reperfusion period. We therefore tested the hypotheses that Y-27632 dilates cerebral pial arterioles after the ischemia-reperfusion injury, and evaluated the time-course of cerebral pial arteriolar status after the ischemia-reperfusion.
  
  
  
  Japanese white rabbits were anesthetized with propofol, and a closed cranial window inserted over the left hemisphere. Global brain ischemia was produced by clamping the brachiocephalic, left common carotid, and left subclavian arteries for 15 min. Rabbits were assigned to cranial window perfusion with: (1) artificial cerebrospinal fluid (Control group, n = 7); (2) topical infusion of Y-27632 10-6mol · L-1for 30 min before the initiation of global brain ischemia (Pre group, n = 7); (3) topical infusion of Y-27632 10-6mol · L-1starting 30 min before ischemia and continuing throughout the study period (Continuous group, n = 7); and, (4) topical infusion of Y-27632 10-6mol · L-1starting 10 min after the ischemia and continuing until the end of the study (Post group, n = 7). Cerebral pial arterial and venule diameters were recorded 30 min before ischemia, just before arterial clamping, 10 min after clamping, and 5, 10, 20, 40, 60, 80, 100, and 120 min after unclamping.
  
  
  
  Mean arterial blood pressure and blood glucose concentration increased significantly after global brain ischemia except in the Continuous group. In the Pre and Continuous groups, topical application of Y-27632 produced dilation of large (mean 18-19%) and small (mean; 25-29%) pial arteries, without apparent effect on venules. Compared with the Control and Pre groups, arterioles were significantly dilated during the reperfusion period in the Continuous and Post groups (mean at 120 min: 5-8% in large arterioles and 11-12% in small arterioles).
  
  
  
  Y-27632 dilated cerebral pial arterioles during reperfusion. Y-27632 may enhance recovery from ischemia by preventing arteriolar vasoconstriction during reperfusion.
authors.affiliation: Surgical Center, University of Yamanashi Hospital, 1110 Shimokato, Chuo, 409-3898, Yamanashi, Japan. nshin0701@yahoo.co.jp.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Shintani
authors.affiliation: Surgical Center, University of Yamanashi Hospital, 1110 Shimokato, Chuo, 409-3898, Yamanashi, Japan.
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Ishiyama
authors.affiliation: Department of Anesthesiology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, 409-3898, Yamanashi, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kotoda
authors.affiliation: Department of Anesthesiology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, 409-3898, Yamanashi, Japan.
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Asano
authors.affiliation: Department of Outcomes Research, Cleveland Clinic, Anesthesiology Institute, Cleveland, OH, USA.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Sessler
authors.affiliation: Department of Anesthesiology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, 409-3898, Yamanashi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsukawa
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000097:blood* / Q000150:complications; D055806:Microvessels / Q000187:drug effects*; D010841:Pia Mater / Q000098:blood supply*; D015742:Propofol / Q000009:adverse effects; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000150:complications / Q000517:prevention & control*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000577:Amides; D001786:Blood Glucose; D011725:Pyridines; C108830:Y 27632; D015742:Propofol
keywords: Cranial window; Global brain ischemia-reperfusion; Y-27632