4.6 Article

Effects of sildenafil on the fetal growth of guinea pigs and their ability to survive induced intrapartum asphyxia

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DOI: 10.1016/j.ajog.2007.06.068

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fetal body weight; fetal organ maturity; fetal structures; guinea pigs; preclinical drug evaluations

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OBJECTIVE: Our goal was to determine whether sildenafil increased fetal weight and favored fetal tolerance to induced asphyxia at birth in guinea pigs. STUDY DESIGN: Twenty guinea pigs were randomly allocated to placebo (n = 10) or sildenafil 50 mu g/kg (n = 5) or 500 mu g/ kg (n = 5), starting from day 35 of gestation to delivery. Fetuses were delivered by cesarean section. Fetal asphyxia was induced by clamping the umbilical cord at birth for 5 minutes. RESULTS: Sildenafil protected the pups against induced asphyxia at birth in a dose-dependent manner (eg, partial pressure (tension) of carbon dioxide levels were 75.9 +/- 19.3, 66.9 +/- 18.8, and 54.8 +/- 13.0 in the control and low- and high-dose sildenafil groups, respectively). The high-dose sildenafil group of piglets gained 1.5 times more body weight. CONCLUSION: In guinea pigs, low doses of sildenafil administered from day 35 to the end of gestation favored fetal tolerability to induced intrapartum asphyxia. High doses of sildenafil increased fetal weight.

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