107 Intrauterine infusions of Flunixin Meglumine on gestational day 30 resulted in pregnancy loss in beef cows

Abstract The physiological mechanisms underlying late embryonic/early fetal mortality in beef cows are largely unknown. Our lab, as well as others, have documented that cows undergoing late embryonic mortality have significantly decreased circulating concentrations of prostaglandin F2a metabolite (PGFM) and increased concentrations of prostaglandin E2 metabolite (PGEM) during gestational d 30 to 38, coinciding with the time of active placentation. Thus, the overall objective of this study was to analyze the physiological effect of inhibiting local prostaglandin synthesis during late embryonic development in beef cows. To determine the appropriate dosage and drug required for the sufficient knockdown of uterine-derived prostaglandins, three pilot studies were conducted. In pilot study one and two, indomethacin was administered intravenously or intrauterine into cyclic cows at a dose of 80 mg/d (n = 4) or, 160 mg/d (n = 4), directly into the jugular of pregnant cows at a dose of 270 mg/d (n = 1) or directly into the uterine artery of pregnant cows at a dose 360 mg/d (n = 2). Administration of indomethacin did not significantly knockdown PGFM or PGEM (P > 0.05). However, in pilot study three, a 720 mg/d dose of flunixin meglumine (FM; Banamine, Merck Animal Health, NJ) infused intrauterine into cyclic beef cows (n = 5) resulted in a treatment by day interaction (P < 0.001) in which luteolysis in treatment cows was inhibited as well as the synthesis of both prostaglandin F2a and prostaglandin E2. Following this validation, the next study was performed using multiparous beef cows that were subjected to a 7-d CO-Synch + CIDR synchronization protocol with insemination occurring on d 0. Pregnancy was confirmed by the presence of a fetal heartbeat on d 28 via ultrasonography and subsequent blood collections every 8 h via venipuncture (n = 9). Intrauterine infusions began on d 29 and occurred every 8 h via infusette catheter consisting of either 240 mg of FM diluted in 10 mL of flush media (ABT; FMTrt; n = 6), or 10 mL of flush media (CON; n = 3). Both infusion solutions were corrected to a pH of 7.4. Serum concentrations of PGFM were measured with a validated commercial ELISA (Cayman Chemical, MI). Though all cows were confirmed pregnant on d 28, concentrations of PGFM were significantly greater on d 28 (P < 0.01) and d 29 (P < 0.05) in the FMTrt cows than the CON cows. There was a significant decline in circulating PGFM within the FMTrt cows (P < 0.05) post infusion on d 29. After two infusions, CON cows had significantly greater PGFM concentrations compared with the FMTrt group (P < 0.01). By d 30, after three infusions, all FMTrt cows had terminated their pregnancies; however, CON cows maintained their pregnancies. Perhaps, these data indicate the importance of prostaglandins during this critical period of pregnancy. Further research is required to fully understand the physiological contribution that prostaglandins elicit in regard to pregnancy.