CEREBROVASCULAR PROSTANOID PRODUCTION IN NEONATAL GROUP B STREPTOCOCCAL MENINGITIS. † 1777

Abstract

Group B Streptococcal (GBS) meningitis impairs cerebral blood flow (CBF) autoregulation in newborn piglets. We determined whether the early impairment could be related to increased prostaglandin (PG) production and if dexamethasone and ibuprofen alter PG production in the early phase (1st 6 hrs) of GBS meningitis. Net cerebrovascular PG production (calculated as total CBF× (sagittal-arterial plasma PG concentration) of 6-keto-PGF1α (stable metabolite of prostacyclin), TXB2(thromboxane B2) and PGE2 were measured in 4 groups of piglets given either 1) saline 0.5 ml intracerebroventrically (icv, control grp, n=9), 2) GBS alone (109 cfu/0.5 ml GBS icv, n=7), or 3) GBS icv plus dexamethasone (DEX) 1 mg/kg intraarterial, ia, n=8) or 4) GBS icv plus ibuprofen (IBU) 30 mg/kg ia,n=7) during periods of normotension (MABP= 50-90 mmHg), hypotension (MABP 90mmHg). MABP was randomly adjusted by balloon tipped catheters in the aortic root and descending aorta. CBF was measured by radioactive microsphere technique and PG's were measured by radioimmunoassay. Results show that within each treatment group there was a decrease in cerebrovascular production of 6 keto-PGF1α, TXB2 and PGE2 (p < 0.05) during hypotension possibly due to relative depletion in tissue oxygen for cyclo-oxygenation of arachidonate. However, between treatment groups (Control, GBS alone, GBS+DEX, and GBS+IBU) PG production did not change with BP adjustments except for increased PGE2 during cerebral hypertension(mean±SD, PGE2=250±25 ng/min/100 g brain tissue) compared to hypotension in GBS alone (PGE2=325±30 ng/min/100 g brain, p< 0.05). Irrespective of MABP, cerebral PG production is highest for PGE2, followed by 6-keto PGF1α with no production of TXB2. Since cerebral PG production is minimally influenced by GBS with or without DEX or IBU over a wide range of cerebral perfusion pressures, we suggest that vasoactive mediators other than PG's may mediate CBF impairment in early meningitis. Thus, treatment directed to PG's may not prevent CBF impairment in neonatal GBS meningitis.