Effects of prostaglandins and indomethacin on cerebral blood flow and cerebral oxygen consumption of conscious newborn piglets

Abstract

The effects of the prostaglandins (PG) PGE1, PGE2, PGF2 alpha and PGI2, and of indomethacin on cerebral blood flow (CBF) and cerebral metabolic rate for O2 (CMRO2) were studied in 60 1- to 3-day-old conscious piglets. Effects of PGs in indomethacin-treated animals were also measured. CBF was measured by radiolabelled microspheres prior to and 45 s after intracarotid bolus injections of 0.1-10 micrograms/kg PGE1 and 0.01-1 micrograms/kg PGE2, PGF2 alpha and PGI2. PGE1 decreased CBF by 30% at the dose of 0.1 micrograms/kg and increased it by 39.5% (n = 6) at the higher dose of 10 micrograms/kg. PGE2 (n = 6) increased CBF at all doses administered. PGF2 alpha (0.01 micrograms/kg, n = 8), which is a potent cerebral vasoconstrictor in adults, and PGI2 (0.1 micrograms/kg, n = 6) significantly increased CBF in newborn piglets (p less than 0.05). CMRO2 correlated with CBF in all groups of animals, except for those injected with PGI2. Indomethacin (3 mg/kg i.v.) decreased CBF by 39% (p less than 0.01, n = 6). This effect was partially reversed by PGI2, but not by PGE1 and PGF2 alpha. Sagittal venous blood and arterial-sagittal venous blood differences in concentrations of PGF2 alpha, but not of PGE and 6-keto-PGF1 alpha, correlated weakly but positively (r = 0.4, p less than 0.05) with CBF in indomethacin-treated piglets. These data indicate that PGs exert significant effects on cerebral circulation in the newborn. Primary PGs are principally cerebral vasodilators and are devoid of vasoconstrictive effects in the newborn, except for PGE1 which produces vasoconstriction at low dose (0.1 micrograms/kg). Thus, we speculate that a relative deficiency in cerebral vasoconstrictor effect of PGs may contribute to the reduced upper limit of the CBF autoregulatory range of the newborn.