The effects of caffeine on the preterm sheep ductus arteriosus

Caffeine and other methyl xanthines are widely used in the neonatal period. A recent, randomized, placebo-controlled, multicenter trial found that infants who were randomly assigned to caffeine treatment had less need for pharmacologic and/or surgical closure of a patent ductus arteriosus (PDA). We hypothesized that the decreased need for pharmacologic and surgical closure of the PDA after caffeine treatment might be due to a direct effect of caffeine on ductus contractility. We examined preterm fetal lamb ductus arteriosus (from 24 fetuses, 105 +/- 4 d of gestation, term = 147 d), in vitro to determine the direct effects of caffeine on the isometric tension of the ductus arteriosus. Caffeine (0.003-0.3 mM) had no direct effect on ductus arteriosus tension, nor did it affect the contractile response of the ductus arteriosus to increasing oxygen concentrations. Caffeine's lack of effect was observed in both the presence and absence of indomethacin and NG-nitro-L-arginine methyl ester (L-NAME) (inhibitors of prostaglandin and nitric oxide production). In conclusion, we found no evidence of a direct effect of therapeutic caffeine concentrations on ductus contractility.