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 with ligation of the carotid artery and jugular vein (simulating pre-extracorporeal membrane oxygenation [ECMO] events) on cerebral autoregulation in the newborn lamb. Design: Animal studies, using the newborn lamb, with comparison of two randomized treatment groups. Subjects: 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) Setting: Work was conducted in the research laboratories of the Department of Anesthesiology, Critical Care Medicine at The Johns Hopkins Medical Institutions, Baltimore, MD. Interventions: 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%; 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 artificial cerebrospinal fluid into an intracranial pressure catheter in the lateral ventricle of the brain. Measurements: Studies were taken at four 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 flow was measured using the radiolabeled microsphere technique. Cerebral oxygen consumption, fractional oxygen extraction, and oxygen transport values were calculated at each study period. Main 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 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 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 less than or equal to 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.