Theresa Tacy

Publication Details

  • Combined treatment with a nonselective nitric oxide synthase inhibitor (L-NMMA) and indomethacin increases ductus constriction in extremely premature newborns PEDIATRIC RESEARCH Keller, R. L., Tacy, T. A., Fields, S., Ofenstein, J. P., Aranda, J. V., Clyman, R. I. 2005; 58 (6): 1216-1221

    Abstract:

    Studies in premature animals suggest that 1) prolonged tight constriction of the ductus arteriosus is necessary for permanent anatomic closure and 2) endogenous nitric oxide (NO) and prostaglandins both play a role in ductus patency. We hypothesized that combination therapy with an NO synthase (NOS) inhibitor [N(G)-monomethyl-L-arginine (L-NMMA)] and indomethacin would produce tighter ductus constriction than indomethacin alone. Therefore, we conducted a phase I and II study of combined treatment with indomethacin and L-NMMA in newborns born at <28 weeks' gestation who had persistent ductus flow by Doppler after an initial three-dose prophylactic indomethacin course (0.2, 0.1, 0.1 mg/kg/24 h). Twelve infants were treated with the combined treatment protocol [three additional indomethacin doses (0.1 mg/kg/24 h) plus a 72-hour L-NMMA infusion]. Thirty-eight newborns received three additional indomethacin doses (without L-NMMA) and served as a comparison group. Ninety-two percent (11/12) of the combined treatment group had tight ductus constriction with elimination of Doppler flow. In contrast, only 42% (16/38) of the comparison group had a similar degree of constriction. L-NMMA infusions were limited in dose and duration by acute side effects. Doses of 10-20 mg/kg/h increased serum creatinine and systemic blood pressure. At 5 mg/kg/h, serum creatinine was stable but systemic hypertension still limited L-NMMA dose. We conclude that combined inhibition of NO and prostaglandin synthesis increased the degree of ductus constriction in newborns born at <28 weeks' gestation. However, the combined administration of L-NMMA and indomethacin was limited by acute side effects in this treatment protocol.

    View details for DOI 10.1203/01.pdr.0000183659.20335.12

    View details for Web of Science ID 000233416500014

    View details for PubMedID 16306196

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