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Non-specific inhibition of prostaglandin (PG) synthesis reduces elevated pulmonary artery pressure (PAP) in animal models of newborn sepsis. We hypothesized that Tx was the PG which mediated the septic pulmonary hypertension, and investigated the effects of selective inhibition of Tx synthetase during Group B Streptococcal (GBS) sepsis in piglets.4 piglets were anesthetized, intubated, ventilated and instrumented. Plasma Tx and prostacycl in (PC) metabol i tes were determined by RIA. Pulmonary hypertension was induced by continuous infusion of GBS. After induction of sepsis, PAP rose from 13+2 (SEM) to 4255 mmHg, and cardiac output (CO) dropped from 104F6 to 52+6. BP remained unchanged. Concurrently, TxB levels rose from 45ik264 to 3370t610 pg/ml (p<0.05) and 6 keto ~G F~~ levels rose from 323+55 to 13225569.While GBS infusion continued, a thromboxane synthetase inhibitor, dazemgrel (Dz)(UK 38485) was then administered at 1 mg/kg. In response to treatment, PAP decreased rapidly to 16+1 mmHg, BP and CO remained stable. TxB2 levels dropped to 1960+3C0 and 6 keto PGF (a prostacycl in metabol i te) levels increased to 2090+363!~ Conclusions: I.GBS elevated PAP in piglets while raising both TxB, and PC metabol ites. 2.Dz selectively reduced TxB, and shunted pg production towards PC. 3.Dz preferentially dimikished PAP during GBS sepsis. 4.Selective inh~bi tion of specific prostaglandins may benefit septic infants with elevated PAP. DILATOR PROSTAGLANDIN L.EVELS AND INDOMETHACIN RESPON- SIVENESS. Cathy Hammerman, William Zaia, StuartBerger, Elene Strates and Abdul ~ldousany.(Spon. by K.S. Lee) Univ. of Chicago, Dept. of Pediatrics, Chicago, IL Ductal patency in the premature is associated with increased concentrations of dilator prostaglandins. lndomethacin is a general inhibitor of prostaglandin synthesis; therefore, it is more likely to be successful if levels of dilator prostaglandins are elevated than If not. Both 6 keto PGF , a stable metabolite of prostacyclin, and PGE have been demonlvrated to be increased in conjunction with pate$t ductus arteriosus. Plasma levels of these prostaglandins were measured by radioimmunoassay in ten prematures with PDA. Four of the ten infants studied had elevated 6 keto PGF levels (>500 pg/ml). All of these had a complete disappeara$e of their PDA murmur at 48 hours post therapy. Six infants had 6 keto PGF levels within normal limits. Of these, four had no response tbaindmethacin and were surgically ligated, and two had transient decreases in the intensity of their murmurs with subsequent recurrence i n general, varied z'keto PGF 40 hdur response PGE2 la hesanedirectionas 153 None 52 did 6 keto PGF how-160 None

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