title: Effects of xenon and hypothermia on cerebrovascular pressure reactivity in newborn global hypoxic-ischemic pig model.
abstract: Autoregulation of cerebral perfusion is impaired in hypoxic-ischemic encephalopathy. We investigated whether cerebrovascular pressure reactivity (PRx), an element of cerebral autoregulation that is calculated as a moving correlation coefficient between averages of intracranial and mean arterial blood pressure (MABP) with values between -1 and +1, is impaired during and after a hypoxic-ischemic insult (HI) in newborn pigs. Associations between end-tidal CO2, seizures, neuropathology, and PRx were investigated. The effect of hypothermia (HT) and Xenon (Xe) on PRx was studied. Pigs were randomized to Sham, and after HI to normothermia (NT), HT, Xe or xenon hypothermia (XeHT). We defined PRx >0.2 as peak and negative PRx as preserved. Neuropathology scores after 72 hours of survival was grouped as 'severe' or 'mild.' Secondary PRx peak during recovery, predictive of severe neuropathology and associated with insult severity (P=0.05), was delayed in HT (11.5 hours) than in NT (6.5 hours) groups. Seizures were associated with impaired PRx in NT pigs (P=0.0002), but not in the HT/XeHT pigs. PRx was preserved during normocapnia and impaired during hypocapnia. Xenon abolished the secondary PRx peak, increased (mean (95% confidence interval (CI)) MABP (6.5 (3.8, 9.4) mm Hg) and cerebral perfusion pressure (5.9 (2.9, 8.9) mm Hg) and preserved the PRx (regression coefficient, -0.098 (95% CI (-0.18, -0.01)), independent of the insult severity.
authors.affiliation: Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Elavazhagan
authors.initials: E
authors.lastname: Chakkarapani
authors.forename: John
authors.initials: J
authors.lastname: Dingley
authors.forename: Kristian
authors.initials: K
authors.lastname: Aquilina
authors.forename: Damjan
authors.initials: D
authors.lastname: Osredkar
authors.forename: Xun
authors.initials: X
authors.lastname: Liu
authors.forename: Marianne
authors.initials: M
authors.lastname: Thoresen
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D062186:Arterial Pressure / Q000187:drug effects* / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D003627:Data Interpretation, Statistical; D007035:Hypothermia / Q000503:physiopathology*; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology / Q000517:prevention & control*; D007427:Intracranial Pressure / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D012044:Regression Analysis; D034421:Sus scrofa; D014978:Xenon / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D014978:Xenon
references.citation: Stroke. 2008 Apr;39(4):1307-13
references.pmid: 18309163
references.citation: BMJ. 2010 Feb 09;340:c363
references.pmid: 20144981
references.citation: AJR Am J Roentgenol. 1980 Aug;135(2):239-51
references.pmid: 6773321
references.citation: Pediatr Res. 1996 Jan;39(1):48-54
references.pmid: 8825385
references.citation: Pediatr Res. 1996 May;39(5):791-7
references.pmid: 8726230
references.citation: Neurosurgery. 1997 Jul;41(1):11-7; discussion 17-9
references.pmid: 9218290
references.citation: Anesthesiology. 2007 Jun;106(6):1128-33
references.pmid: 17525587
references.citation: Brain Pathol. 1992 Jul;2(3):223-8
references.pmid: 1343837
references.citation: Pediatr Res. 1999 Sep;46(3):274-80
references.pmid: 10473041
references.citation: Pediatr Res. 1990 Jun;27(6):561-5
references.pmid: 2356099
references.citation: Ann Neurol. 2010 Sep;68(3):330-41
references.pmid: 20658563
references.citation: Anesth Analg. 2009 Aug;109(2):451-60
references.pmid: 19608817
references.citation: Theriogenology. 2000 Aug;54(3):371-88
references.pmid: 11051321
references.citation: Pediatr Res. 1994 Dec;36(6):699-706
references.pmid: 7898977
references.citation: Acta Anaesthesiol Scand. 2013 May;57(5):646-53
references.pmid: 23316707
references.citation: Pediatr Res. 1986 Jun;20(6):516-9
references.pmid: 3714361
references.citation: Br J Anaesth. 2000 Feb;84(2):221-5
references.pmid: 10743456
references.citation: Anaesthesia. 2002 Oct;57(10):960-6
references.pmid: 12358954
references.citation: Anesth Analg. 1990 Jul;71(1):49-54
references.pmid: 2363528
references.citation: Neurosurg Focus. 2008 Oct;25(4):E2
references.pmid: 18828700
references.citation: Pediatr Res. 1996 Nov;40(5):738-48
references.pmid: 8910940
references.citation: Ann Neurol. 2003 Jan;53(1):65-72
references.pmid: 12509849
references.citation: Eur J Pediatr. 2006 Sep;165(9):598-604
references.pmid: 16691409
references.citation: Acta Neurochir Suppl. 2005;95:43-9
references.pmid: 16463818
references.citation: Acta Neurochir Suppl. 1998;71:74-7
references.pmid: 9779149
references.citation: Br J Anaesth. 2008 May;100(5):667-75
references.pmid: 18344553
references.citation: J Perinatol. 2011 Nov;31(11):722-9
references.pmid: 21372795
references.citation: J Cereb Blood Flow Metab. 1985 Mar;5(1):126-32
references.pmid: 3972917
references.citation: Dev Med Child Neurol. 1997 Nov;39(11):718-25
references.pmid: 9393884
references.citation: Am J Physiol. 1998 May;274(5):H1495-501
references.pmid: 9612355
references.citation: Acta Paediatr. 1995 Dec;84(12):1414-20
references.pmid: 8645961
references.citation: Acta Paediatr Scand. 1987 May;76(3):394-400
references.pmid: 3604659
references.citation: Stroke. 1991 Feb;22(2):182-9
references.pmid: 1900644
references.citation: Pediatr Res. 1995 May;37(5):667-70
references.pmid: 7603788
references.citation: J Neurosurg Anesthesiol. 1997 Apr;9(2):188-93
references.pmid: 9100192
references.citation: Cerebrovasc Brain Metab Rev. 1990 Summer;2(2):161-92
references.pmid: 2201348
references.citation: Stroke. 2003 Oct;34(10):2404-9
references.pmid: 12947157
references.citation: Pediatrics. 2009 Dec;124(6):e1205-12
references.pmid: 19948619
references.citation: Pediatrics. 2013 Mar;131(3):e950-4
references.pmid: 23420921
references.citation: Arch Dis Child Fetal Neonatal Ed. 1994 Sep;71(2):F103-6
references.pmid: 7979461