Sildenafil citrate and uteroplacental perfusion in fetal growth restriction

Marzieh Vahid Dastjerdi, Sayedehafagh Hosseini, Leila Bayani, Marzieh Vahid Dastjerdi, Sayedehafagh Hosseini, Leila Bayani

Abstract

Background: To determine whether the phosphodiesterase type 5 inhibitor, Sildenafil citrate, affects uteroplacental perfusion.

Materials and methods: Based on a randomized double-blinded and placebo-controlled trial, forty one pregnant women with documented intrauterine growth retardation at 24-37 weeks of gestation were evaluated for the effect of a single dose of Sildenafil citrate on uteroplacental circulation as determined by Doppler ultrasound study of the umbilical and middle cerebral arteries. Statistical analysis included χ(2)-test to compare proportions, and independent-samples t-test and paired student's t-test to compare continuous variables.

Results: Sildenafil group fetuses demonstrated a significant decrease in systolic/diastolic ratios (0.60 [SD 0.40] [95% Cl 0.37-0.84], P=0.000), and pulsatility index (0.12 [SD 0.15] [95% Cl 0.02-0.22], P=0.019) for the umbilical artery and a significant increase in middle cerebral artery pulsatility index (MCA PI) (0.51 [SD 0.60] [95% Cl 0.16-0.85], P=0.008).

Conclusion: Doppler velocimetry index values reflect decreased placental bed vascular resistance after Sildenafil. Sildenafil citrate can improve fetoplacental perfusion in pregnancies complicated by intrauterine growth restriction. It could be a potential therapeutic strategy to improve uteroplacental blood flow in pregnancies with fetal growth restriction (FGR).

Keywords: Cerebroplacental ratio; Doppler flow velocimetry; fetal growth restriction; pulsatility index; resistance index; systolic/diastolic ratio.

Conflict of interest statement

Conflict of Interest: None declared

References

    1. Gagnon R. Placental insufficiency and its consequences. Eur J Obstet Gynecol Reprod Biol. 2003;110:S99–107.
    1. Gilbert JS, Verzwyvelt J, Colson D, Arany M, Karumanchi SA, Granger JP. Recombinant vascular endothelial growth factor 121 infusion lowers blood pressure and improves renal function in rats with placental ischemia-induced hypertension. Hypertension. 2010;55:380–5.
    1. Johnson MR, Anim-Nyame N, Johnson P, Sooranna SR, Steer PJ. Does endothelial cell activation occur with intrauterine growth restriction? BJOG. 2002;109:836–9.
    1. Schiessl B, Kainer F, Oberhoffer R, Jundt K, Friese K. Doppler sonography of the uterine and the cubital arteries in normal pregnancies, preeclampsia and intrauterine growth restriction: evidence for a systemic vessel involvement. J Perinat Med. 2006;34:139–44.
    1. Soregaroli M, Valcamonico A, Scalvi L, Danti L, Frusca T. Late normalisation of uterine artery velocimetry in high risk pregnancy. Euro J Obstet Gynecol Reprod Biol. 2001;95:42–5.
    1. Rosselli M, Keller RJ, Dubey RK. Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. Hum Reprod Update. 1998;4:3–24.
    1. Ramsay B, Sooranna SR, Johnson MR. Nitric oxide synthase activities in human myometrium and villous trophoblast throughout pregnancy. Obstet Gynecol. 1996;87:249–53.
    1. Bewley S, Chard T, Grudzinskas G, Campbell S. The relationship of uterine and umbilical Doppler resistance to fetal and placental protein synthesis in the second trimester. Placenta. 1993;14:663–70.
    1. Nanetti L, Giannubilo SR, Raffaelli F, Curzi CM, Vignini A, Moroni C, et al. Nitric oxide and peroxynitrite platelet levels in women with small-for-gestational-age fetuses. BJOG. 2008;115:14–21.
    1. Miller SL, Loose JM, Jenkin G, Wallace EM. The effects of sildenafil citrate (Viagra) on uterine blood flow and well being in the intrauterine growth-restricted fetus. Am J Obstet Gynecology. 2009;200(102):e1–7.
    1. Wareing M, Myers JE, O’Hara M, Kenny LC, Taggart MJ, Skillern L, et al. Phosphodiesterase-5 inhibitors and omental and placental small artery function in normal pregnancy and pre-eclampsia. Eur J Obstet Gynecology Reprod Biol. 2006;127:41–9.
    1. Ballard SA, Gingell CJ, Tang K, Turner LA, Price ME, Naylor AM. Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. J Urol. 1998;159:2164–71.
    1. Zoma WD, Baker RS, Friedman A, Clark KE. Sildenafil citrate (Viagra) increases uterine blood flow and potentiates estrogen-induced vasodilation. Am J Obstet Gynecol. 2004;190:1291–7.
    1. Jerzak M, Kniotek M, Mrozek J, Górski A. Sildenafil increases successful pregnancies after recurrent miscarriage. Fertil Steril. 2008;90:1848–53.
    1. Jerzak M, Kniotek M, Mrozek J, Górski A, Baranowski W. Sildenafil citrate decreased natural killer cell activity and enhanced chance of successful pregnancy in women with a history of recurrent miscarriage. Fertil Steril. 2008;90:1848–53.
    1. Shekerdemian LS, Ravn HB, Penny DJ. Intravenous sildenafil lowers pulmonary vascular resistance in a model of neonatal pulmonary hypertension. Am J Respir Crit Care Med. 2002;165:1098–102.
    1. Sánchez-Aparicio P, Mota-Rojas D, Nava-Ocampo AA, Trujillo-Ortega ME, Alfaro-Rodríguez A, Arch E, et al. Effects of sildenafil on the fetal growth of guinea pigs and their ability to survive induced intrapartum asphyxia. Am J Obstet Gynecol. 2008;198(127):e1–6.
    1. Lacassie HJ, Germain AM, Valdés G, Fernández MS, Allamand F, López H. Management of Eisenmenger syndrome in pregnancy with sildenafil and L-arginine. Obstet Gynecol. 2004;103:1118–20.
    1. Wareing M, Myers JE, O’Hara M, Baker PN. Sildenafil citrate (Viagra) enhances vasodilatation in fetal growth restriction. J Clin Endocrinol Metab. 2005;90:2550–5.
    1. Bower S, Kingdom J, Campbell S. Objective and subjective assessment of abnormal uterine artery Doppler flow velocity waveforms. Ultrasound Obstet Gynecol. 1998;12:260–4.
    1. Hernandez-Andrade E, Figueroa-Diesel H, Jansson T, Rangel-Nava H, Gratacos E. Changes in regional fetal cerebral blood flow perfusion in relation to hemodynamic deterioration in severely growth-restricted fetuses. Ultrasound Obstet Gynecol. 2008;32:71–6.
    1. Baschat AA, Gembruch U, Reiss I, Gortner L, Weiner CP, Harman CR. Relationship between arterial and venous Doppler and perinatal outcome in fetal growth restriction. Ultrasound Obstet Gynecol. 2000;16:407–13.
    1. Resnik R. Intrauterine growth restriction. Obstet Gynecol. 2002;99:490–6.
    1. Samangaya RA, Mires G, Shennan A, Skillern L, Howe D, McLeod A, et al. A randomised, double-blinded, placebo-controlled study of the phosphodiesterase type 5 inhibitor sildenafil for the treatment of preeclampsia. Hypertens Pregnancy. 2009;28:369–82.
    1. Boyce EG, Umland EM. Sildenafil citrate: A therapeutic update. Clin Ther. 2001;23:2–23.

Source: PubMed

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