IMPAIRED CEREBRAL AUTOREGULATION IN THE NEWBORN LAMB DURING RECOVERY FROM SEVERE, PROLONGED HYPOXIA, COMBINED WITH CAROTID-ARTERY AND JUGULAR-VEIN LIGATION

Objective: To study the effect of severe prolonged hypoxia combined wi th ligation of the carotid artery and jugular vein (simulating pre-ext racorporeal membrane oxygenation [ECMO] events) on cerebral autoregula tion in the newborn lamb. Design: Animal studies, using the newborn la mb, with comparison of two randomized treatment groups. Subjects: Newb orn 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) Setting: Work was conducted in the researc h laboratories of the Department of Anesthesiology, Critical Care Medi cine at The Johns Hopkins Medical Institutions, Baltimore, MD. Interve ntions: Animals were anesthetized (pentobarbital), intubated, and mech anically ventilated. We examined the effect of prolonged severe hypoxi a combined with carotid artery and jugular vein ligation on cerebral a utoregulation during recovery from this insult. Control animals were m aintained in a normoxic state (3 hrs) without carotid artery or jugula r vein ligation. Hypoxic animals with carotid artery and jugular vein ligation were exposed to a 2-hr period of hypoxia (arterial oxygen sat uration 44 +/- 14%; Pao(2) 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 artifi cial cerebrospinal fluid into an intracranial pressure catheter in the lateral ventricle of the brain. Measurements: Studies were taken at f our ranges of cerebral perfusion pressure: > 55 mm Hg; 55 to 40 mm Hg; 39 to 26 mm Hg; and less than or equal to 25 mm Hg. Cerebral blood fl ow was measured using the radiolabeled microsphere technique. Cerebral oxygen consumption, fractional oxygen extraction, and oxygen transpor t values were calculated at each study period. Main Results: Two hours of severe hypoxia increased cerebral blood flow by 110%, whereas cere bral oxygen consumption was unchanged. In hypoxic animals, cerebral au toregulation was altered, with both cerebral blood flow and cerebral o xygen consumption decreasing at a cerebral perfusion pressure of 39 to 26 mm Hg compared with unchanged cerebral blood flow or cerebral oxyg en consumption at a cerebral perfusion pressure of less than or equal to 25 mm Hg in control animals. At the point of loss of autoregulation , significant right-to-left hemispheric cerebral blood flow changes oc curred in hypoxic animals. In hypoxic animals, cerebellar cerebral blo od flow changes were similar to those changes in the total cerebrum, w hile brain stem and caudate decreased cerebral blood flow only at a ce rebral perfusion pressure of less than or equal to 25 mm Hg. Conclusio ns: These findings indicate that cerebral autoregulation is disrupted during the recovery phase from an insult caused by prolonged, severe h ypoxia with carotid artery and jugular vein ligation. This insult resu lts in significant differences in right and left hemispheric cerebral blood flow rates when cerebral autoregulation is lost. If these result s 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 fact or in cerebral injury in ECMO patients.