Endotoxin-induced abortion in early pregnant gilts and its prevention by flunixin meglumine.
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The objective of the study was to examine the effect of endotoxin on early pregnancy in gilts and to test the potential of flunixin meglumine (FM), a cyclooxygenase inhibitor, to counteract abortifacient action of the endotoxin. Ten gilts at 30 days gestation were used in the experiment. Eight were injected with lipopolysaccharide (LPS) of Salmonella typhimurium, while 2 were treated with 500 micrograms cloprostenol (CP). Six of the LPS-injected gilts were treated with a total of 4 mg/kg body weight FM in 2 different dose regimens. Clinical observations were recorded and plasma levels of 15-keto-13, 14-dihydro-PGF2 alpha, progesterone and estrone sulfate (ES) were determined with radioimmunoassay. LPS induced typical signs of endotoxemia and a monophasic fever in all LPS-treated gilts. No antipyretic effect of FM was observed. The CP-treated gilts aborted within 34 h as did the gilts treated by LPS only. Of the 6 LPS + FM-treated gilts, 1 aborted within 34 h, while 5 maintained gestation. These were aborted about a week later by CP and the aborted fetuses anatomically examined. Two of the litters were lost (devoured by the dams), 2 showed no signs of earlier death and 1 showed extensive fetal death. The PGF2 alpha metabolite concentrations increased at least 10 fold immediately after the LPS injection. Progesterone plasma concentration decreased rapidly. A 5-10 fold increase in the plasma metabolite levels accompanied all abortions. CP caused no immediate change in the PGF2 alpha metabolite levels, but the abortion-related response was similar to that in LPS-injected gilts. In the FM-treated gilts, the LPS-induced PGF2 alpha metabolite response was rudimentary and the progesterone decrease temporary in nonaborting gilts. The elevated concentrations of ES decreased within 48 h in gilts aborting at 30 days gestation, while in nonaborting gilts a slow, graduate decrease of ES occurred within 3-5 days of the LPS injection. These results indicate that FM apparently suppressed LPS-induced prostaglandin synthesis and thus prevented luteolysis and abortion in early pregnant gilts.