THE EFFECT OF PGEI, PGF2 AND PGI2 ON CEREBRAL BLOOD FLOW (CBF) AND OXYGEN METABOLISM (CRMO2) OF THE NEWBORN (NB) PIGLET, WITH AND WITHOUT INDOMETHACIN (Id) PRE-TREATMENT

Abstract

A role for PCs in the regulation of CBF of the NB has been ascribed only through indirect evidence. We evaluated the effects of incremental doses of PGE1 (doses: 5, 10−7, 10−6, 10−5 g/kg), PGF2@ and PGI2 (doses: 0, 10−8, 10−7, 10−6 g/kg) q 20 min, with and without Id pre-treatraent, on CBF ( radiolabelled raicrosphere technique) and CRMO2 of 1-3 day old awake piglets. Total CBF is presented. Similar changes were seen for the eyes and 13 brain regions. Blood gases, aortic pressure and cardiac output remained stable. PGE1 doses of 10−7 g/kg decreased CBF by 10 %, and 10−5 g/kg increased CBF by 39.5 % (n=6). PGF2@ (10−8 g/kg) (n=8), a potent adult cerebral vasoconstrictor, and PGI2 (10−7 g/kg) (n=6) increased CBF, (P < 0.05 and P < 0.01, respectively). Id (3 mg/kg IV, 5 mins post baseline CBF determination) decreased CBF by 38 % (P < 0.02; n=6). Only PGI2 (10−8 and 10−7 g/kg) reversed (partially) the CBF decrease induced by Id (P < 0.04; n = 6). CBF did not change in 7 controls. CRMO2 correlated with CBF in all groups (r = 0.69-0.87, P < 0.0001), except for PGI2. The findings imply that: 1) Ontogenic changes in receptor binding or population, and/or post-receptor events may explain the opposite CBF responses to PGF2@ in the NB and adult; 2) In the presence of elevated perinatal PG plasma levels, the NB is devoid of local cerebrovascular constrictor PG, possibly contributing to its narrow CBF autoregulatory range.