Increased Constriction of the Ductus Arteriosus by Dexamethasone, Indomethacin, and Rofecoxib in Fetal Rats

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Background To find a better treatment for patent ductus arteriosus (PDA) in premature infants, the present study investigated the synergism of clinical doses of dexamethasone, indomethacin, and rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on the fetal ductus arteriosus (DA) in rats. Methods and Results Dexamethasone (0.3mg/kg), indomethacin (0.3mg/kg), and rofecoxib (0.3mg/kg), alone or in combination, were administered to preterm (d19) and near-term (d21) fetal rats. The ratio of the inner diameter of the DA to that of the main pulmonary artery (PA) (DA/PA) was studied at 2, 4 and 8h after drug administration, using a rapid whole-body freezing method. In near-term rats, the combined administration of dexamethasone and indomethacin caused severe constriction, with a DA/PA ratio of 0.52±0.08 at 8h, whereas the DA/PA ratios were 0.83±0.03 and 0.90±0.02 with dexamethasone and indomethacin, respectively. Combined administration of dexamethasone and rofecoxib also caused severe constriction, with a DA/PA ratio of 0.64±0.07 at 8h, compared with the DA/PA ratio of 0.92±0.03 with rofecoxib alone. Conclusions Combined therapy may be an option in the medical management of PDA in premature infants before considering surgical treatment.
社団法人日本循環器学会の論文
2005-02-20