title: Impaired cerebral autoregulation in the newborn lamb during recovery from severe, prolonged hypoxia, combined with carotid artery and jugular vein ligation.
abstract: OBJECTIVE
  To study the effect of severe prolonged hypoxia combined with ligation of the carotid artery and jugular vein (simulating pre-extracorporeal membrane oxygenation [ECMO] events) on cerebral autoregulation in the newborn lamb.
  
  
  METHODS
  Animal studies, using the newborn lamb, with comparison of two randomized treatment groups.
  
  
  METHODS
  Newborn lambs of mixed breed, 1 to 7 days of age, were used for the study. Two groups of animals were studied: a normoxic control group (n = 7) and a hypoxic group (n = 8).
  
  
  METHODS
  Work was conducted in the research laboratories of the Department of Anesthesiology, Critical Care Medicine at The Johns Hopkins Medical Institutions, Baltimore, MD.
  
  
  METHODS
  Animals were anesthetized (pentobarbital), intubated, and mechanically ventilated. We examined the effect of prolonged severe hypoxia combined with carotid artery and jugular vein ligation on cerebral autoregulation during recovery from this insult. Control animals were maintained in a normoxic state (3 hrs) without carotid artery or jugular vein ligation. Hypoxic animals with carotid artery and jugular vein ligation were exposed to a 2-hr period of hypoxia (arterial oxygen saturation 44 +/- 14%; PaO2 30 +/- 3 torr [4 +/- 0.4 kPa]) followed by a 1-hr normoxic recovery period. Cerebral autoregulation was evaluated at the end of the 1-hr recovery period in hypoxic animals, and after 3 hrs of normoxia in control animals. Cerebral perfusion pressure was decreased by increasing intracranial pressure, with infusion of artificial cerebrospinal fluid into an intracranial pressure catheter in the lateral ventricle of the brain.
  
  
  METHODS
  Studies were taken at four ranges of cerebral perfusion pressure: > 55 mm Hg; 55 to 40 mm Hg; 39 to 26 mm Hg; and < or = 25 mm Hg. Cerebral blood flow was measured using the radiolabeled microsphere technique. Cerebral oxygen consumption, fractional oxygen extraction, and oxygen transport values were calculated at each study period.
  
  
  RESULTS
  Two hours of severe hypoxia increased cerebral blood flow by 110%, whereas cerebral oxygen consumption was unchanged. In hypoxic animals, cerebral autoregulation was altered, with both cerebral blood flow and cerebral oxygen consumption decreasing at a cerebral perfusion pressure of 39 to 26 mm Hg compared with unchanged cerebral blood flow or cerebral oxygen consumption at a cerebral perfusion pressure of < or = 25 mm Hg in control animals. At the point of loss of autoregulation, significant right-to-left hemispheric cerebral blood flow changes occurred in hypoxic animals. In hypoxic animals, cerebellar cerebral blood flow changes were similar to those changes in the total cerebrum, while brain stem and caudate decreased cerebral blood flow only at a cerebral perfusion pressure of < or = 25 mm Hg.
  
  
  CONCLUSIONS
  These findings indicate that cerebral autoregulation is disrupted during the recovery phase from an insult caused by prolonged, severe hypoxia with carotid artery and jugular vein ligation. This insult results in significant differences in right and left hemispheric cerebral blood flow rates when cerebral autoregulation is lost. If these results can be extrapolated to the human state, they may help to explain the role of pre-ECMO hypoxia combined with vessel ligation as a risk factor in cerebral injury in ECMO patients.
authors.affiliation: Department of Pediatrics, George Washington University School of Medicine, Washington, DC.
authors.forename: B L
authors.initials: BL
authors.lastname: Short
authors.forename: L K
authors.initials: LK
authors.lastname: Walker
authors.forename: R J
authors.initials: RJ
authors.lastname: Traystman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001783:Blood Flow Velocity; D001784:Blood Gas Analysis; D002339:Carotid Arteries / Q000601:surgery*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D015199:Extracorporeal Membrane Oxygenation / Q000009:adverse effects*; D006439:Hemodynamics / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D002534:Hypoxia, Brain / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D007427:Intracranial Pressure / Q000502:physiology; D007601:Jugular Veins / Q000601:surgery*; D008026:Ligation; D010101:Oxygen Consumption / Q000502:physiology; D012720:Severity of Illness Index; D012756:Sheep; D013997:Time Factors