THE ROLE OF PROSTANOIDS IN NEONATAL CEREBRAL BLOOD-FLOW AUTOREGULATION

The regulatory role of prostanoids in acute cerebrovascular adaptation s in newborns was determined using awake neonatal piglets (ages 0-5 da ys, n = 60). Cerebral blood flow (CBF) was measured by radiolabelled m icrospheres before and 45 s after intracarotid injections of PGE1 (0.1 -10 mug/kg, n = 6), PGE2 (0.01-2 mug/kg, n = 6), PGF2alpha (0.01 mug/k g, n = 8) and PGI2 (0.1 mug/kg, n = 6). CBF increased with PGE1 (10 mu g/kg) by 39.5% and with all doses of PGE2 (p < 0.01) compared to zero dose. PGF2alpha, a known adult vasoconstrictor increased total CBF fro m 97 +/- 8 to 130 +/- 14 ml/min per kg. PGI2 also increased CBF by 27% (p < 0.01). When CBF and prostanoid levels were measured with balloon catheters placed at the aortic root and the descending aorta and were inflated to adjust arterial blood pressure (BP) from 17 to 117 mmHg, sagital sinus concentrations of prostanoids inversely correlated with total CBF (for PGS, tau = -0.52 to -0.66, p < 0.001; for TXB2, tau = - 0.91 to 0.99, p < 0.0001). During hypotension (MABP < 50 mmHg) PGE, PG F2(2alpha), 6-keto-PGF1alpha and TXB2 increased by 311 +/-56, 330 +/- 50, 301 +/- 44 and 658 +/- 44%, respectively. Net cerebrovascular prod uction [total CBF x (sagittal sinus-arterial plasma prostanoid concent ration)] of PGE, PGF2alpha, and 6-ketoPGF1alpha and TXB2 increased dur ing hypotension compared to normotension (BP = 50-90 mmHg). At MABP = 91-117 mmHg, net production of prostanoids increased by 142-31%. Howev er, TXB2 production was only observed with hypotension and not with hy pertension. Non-linear polynomial function analysis of CBF and MABP sh ow that total and regional CBF were constant at MABP = 50-90 mmHg and varied directly with BP below and above this range (tau = 0.42-0.51, p < 0.05). Treatment with ibuprofen (30 mg/kg), a cyclo-oxygenase inhib itor, abolished the flow-pressure correlations and widened the autoreg ulatory curve. Data indicate that prostanoids are vasorelaxants in the newborn with negligible vasoconstrictor function at high systemic pre ssures. These lead to shifts in the autoregulatory curve resulting in narrowing of range of neonatal autoregulation. Cyclo-oxygenase inhibit ion increased the range of CBF autoregulation suggesting a possible lo cus for future clinical pharmacologic interventions.