American Journal of Obstetrics & Gynecology
Volume 200, Issue 1 , Pages 102.e1-102.e7 , January 2009

The effects of sildenafil citrate (Viagra) on uterine blood flow and well being in the intrauterine growth-restricted fetus

  • Suzanne L. Miller, PhD

      Affiliations

    • Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, VIC, Australia
    • Department of Physiology, Monash University, Clayton, VIC, Australia
    • Corresponding Author InformationReprints: Suzanne L. Miller, PhD, Department of Physiology, Building 13F, Monash University, Clayton 3800, VIC, Australia
    • ,
  • Jan M. Loose, BSc

      Affiliations

    • Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, VIC, Australia
    • ,
  • Graham Jenkin, PhD

      Affiliations

    • Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, VIC, Australia
    • ,
  • Euan M. Wallace, MD

      Affiliations

    • Department of Obstetrics and Gynecology Monash Institute of Medical Research, Monash University, Clayton, VIC, Australia

Received 18 April 2008 ,Revised 19 June 2008 ,Accepted 8 August 2008.

References 

  1. Marlow N. Paediatric implications—neonatal complications. In:  Kingdom J,  Baker P editor. Intrauterine growth restriction: aetiology and management. London: Springer; 2000;p. 337–349
  2. Gagnon R. Placental insufficiency and its consequences. Eur J Obstet Gynecol Reprod Biol. 2003;110:S99–S107
  3. van Wassenaer A. Neurodevelopmental consequences of being born SGA. Pediatr Endocrinol Rev. 2005;2:372–377
  4. Baschat AA. Doppler application in the delivery timing of the preterm growth-restricted fetus: another step in the right direction. Ultrasound Obstet Gynecol. 2004;23:111–118
  5. Roberts JM, Taylor RN, Musci TJ, Rodgers GM, Hubel CA, McLaughlin MK. Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol. 1989;161:1200–1204
  6. Johnson MR, Anim-Nyame N, Johnson P, Sooranna SR, Steer PJ. Does endothelial cell activation occur with intrauterine growth restriction?. BJOG. 2002;109:836–839
  7. Pinheiro da Costa BE, Scocco C, Poli de Figueiredo CE, Guimaraes JA. Increased serum phosphodiesterase activity in women with pre-eclampsia. BJOG. 2006;113:577–579
  8. Briganti A, Salonia A, Deho F, Zanni G, Barbieri L, Rigatti P, et al. Clinical update on phosphodiesterase type-5 inhibitors for erectile dysfunction. World J Urol. 2005;23:374–384
  9. Wareing M, Myers JE, O'Hara M, et al. Effects of a phosphodiesterase-5 (PDE5) inhibitor on endothelium-dependent relaxation of myometrial small arteries. Am J Obstet Gynecol. 2004;190:1283–1290
  10. Wareing M, Myers JE, O'Hara M, et al. Phosphodiesterase-5 inhibitors and omental and placental small artery function in normal pregnancy and pre-eclampsia. Eur J Obstet Gynecol Reprod Biol. 2006;127:41–49
  11. Supramaniam VG, Jenkin G, Loose J, Wallace EM, Miller SL. Chronic fetal hypoxia increases activin A concentrations in the late-pregnant sheep. BJOG. 2006;113:102–109
  12. Oyama K, Padbury J, Chappell B, Martinez A, Stein H, Humme J. Single umbilical artery ligation-induced fetal growth retardation: effect on postnatal adaptation. Am J Physiol. 1992;263:E575–E583
  13. Resnik R. Intrauterine growth restriction. Obstet Gynecol. 2002;99:490–496
  14. Miller SL, Chai M, Loose J, et al. The effects of maternal betamethasone administration on the intrauterine growth-restricted fetus. Endocrinology. 2007;148:1288–1295
  15. Miller SL, Jenkin G, Walker DW. Effect of nitric oxide synthase inhibition on the uterine vasculature of the late-pregnant ewe. Am J Obstet Gynecol. 1999;180:1138–1145
  16. Noori S, Friedlich P, Wong P, Garingo A, Seri I. Cardiovascular effects of sildenafil in neonates and infants with congenital diaphragmatic hernia and pulmonary hypertension. Neonatology. 2007;91:92–100
  17. Leibovitch L, Matok I, Paret G. Therapeutic applications of sildenafil citrate in the management of paediatric pulmonary hypertension. Drugs. 2007;67:57–73
  18. Villanueva-Garcia D, Mota-Rojas D, Hernandez-Gonzalez R, et al. A systematic review of experimental and clinical studies of sildenafil citrate for intrauterine growth restriction and pre-term labour. J Obstet Gynaecol. 2007;27:255–259
  19. Nagdyman N, Fleck T, Bitterling B, et al. Influence of intravenous sildenafil on cerebral oxygenation measured by near-infrared spectroscopy in infants after cardiac surgery. Pediatr Res. 2006;59:462–465
  20. Coppage KH, Sun X, Baker RS, Clark KE. Expression of phosphodiesterase 5 in maternal and fetal sheep. Am J Obstet Gynecol. 2005;193:1005–1010
  21. Zoma WD, Baker RS, Clark KE. Effects of combined use of sildenafil citrate (Viagra) and 17beta-estradiol on ovine coronary and uterine hemodynamics. Am J Obstet Gynecol. 2004;190:1291–1297
  22. Refuerzo JS, Sokol RJ, Aranda JV, et al. Sildenafil citrate and fetal outcome in pregnant rats. Fetal Diagn Ther. 2006;21:259–263
  23. Khan RN, Hamoud H, Warren A, Wong LF, Arulkumaran S. Relaxant action of sildenafil citrate (Viagra) on human myometrium of pregnancy. Am J Obstet Gynecol. 2004;191:315–321
  24. Wareing M, Myers JE, O'Hara M, Baker PN. Sildenafil citrate (Viagra) enhances vasodilatation in fetal growth restriction. J Clin Endocrinol Metab. 2005;90:2550–2555
  25. Lumbers ER. Effects of drugs on uteroplacental blood flow and the health of the foetus. Clin Exp Pharmacol Physiol. 1997;24:864–868
  26. Greiss FC, Marston EL. The uterine vascular bed: effect of estrogens during ovine pregnancy. Am J Obstet Gynecol. 1965;93:720–722
  27. Lin CS, Lin G, Xin ZC, Lue TF. Expression, distribution and regulation of phosphodiesterase 5. Curr Pharm Des. 2006;12:3439–3457
  28. Boyce EG, Umland EM. Sildenafil citrate: a therapeutic update. Clin Ther. 2001;23:2–23
  29. Hanson KA, Ziegler JW, Rybalkin SD, Miller JW, Abman SH, Clarke WR. Chronic pulmonary hypertension increases fetal lung cGMP phosphodiesterase activity. Am J Physiol. 1998;275:L931–L941
  30. Supramaniam VG, Jenkin G, Wallace EM, O'Connor AE, de Kretser DM, Miller SL. Effect of graded hypoxia on activin A, prostaglandin E2 and cortisol levels in the late-pregnant sheep. Reprod Fertil Dev. 2004;16:625–632
  31. Giussani DA, Unno N, Jenkins SL, et al. Dynamics of cardiovascular responses to repeated partial umbilical cord compression in late-gestation sheep fetus. Am J Physiol. 1997;273:H2351–H2360

 This study was supported in part by a program grant from the National Health and Medical Research Council of Australia (to G.J. and E.M.W.).

 Cite this article as: Miller SL, Loose JM, Jenkin G, et al. The effects of sildenafil citrate (Viagra) on uterine blood flow and well being in the intrauterine growth-restricted fetus. Am J Obstet Gynecol 2009;200:102.e1-102.e7.

PII: S0002-9378(08)00931-9

doi: 10.1016/j.ajog.2008.08.029

American Journal of Obstetrics & Gynecology
Volume 200, Issue 1 , Pages 102.e1-102.e7 , January 2009

Article Tools

* Image Usage & Resolution