THE INFLUENCE OF INDOMETHACIN ON THE AUTOREGULATORY ABILITY OF THE CEREBRAL VASCULAR BED IN THE NEWBORN LAMB

Prevention of hyperperfusion of the brain in the perinatal period has been thought to be an important mechanism by which indomethacin reduce s the risk for severe periventricular-intraventricular hemorrhage. The present study investigated whether an indomethacin-induced enhancemen t of the upper limit of cerebral vascular autoregulatory ability in th e neonate contributed to this reduction in cerebral blood flow. In sev en anesthetized newborn lambs, we measured temporal blood flow velocit y (TMFV) in the carotid artery over a wide range of mean aortic blood pressures (MABP) before and 30 min after an i.v. dose of 1 mg/kg indom ethacin. TMFV in the carotid artery was used as an estimate for change s in cerebral blood flow. Stepwise changes in MABP of approximately 10 mm Hg were achieved by progressive balloon occlusion of the thoracic aorta or by progressive bleeding. Multiple linear regression analysis of TMFV versus MABP, indomethacin, and the possible interactive effect s confirmed that, at MABP values up to 86 mm Hg, indomethacin lowered TMFV of the carotid artery. Above 86 mm Hg, indomethacin reduced the s lope of the TMFV-MABP relationship, indicating an improvement of the a utoregulatory ability of the cerebral vascular bed. There was a signif icant interanimal variability. Thus, indomethacin may reduce the risk for PIVH by limiting cerebral blood flow, especially during increased cerebral perfusion pressures, which often occur after birth asphyxia.