Effect of dual tocolysis with fenoterol and atosiban in human myometrium
-
Bernhard Stoiber
,
Christian Haslinger
Abstract
Objectives
To measure the tocolytic effect of the combination of the oxytocin receptor antagonist atosiban with the β-mimetic agent fenoterol on human myometrium of pregnant women.
Methods
An in vitro study of contractility in human myometrium at the Laboratory of the Department of Obstetrics, University Hospital of Zürich, Switzerland, was performed. Thirty-six human myometrial biopsies were obtained during elective caesarean sections of singleton pregnancies at term. Tissue samples were exposed to atosiban, fenoterol and the combination of atosiban with fenoterol. Contractility was measured as area under the curve during 30 min of spontaneous contractions. The effect of treatment was expressed as the percentage of change from basal activity during 30 min of exposure. Differences were calculated using a paired Wilcoxon signed-rank test. An additive effect of dual tocolysis was assumed when no significant difference was detected between the observed and expected inhibition of dual tocolysis. When inhibition was greater or lower than expected, the dual combination was characterised as “synergistic” or “antagonistic”, respectively.
Results
Atosiban and fenoterol alone suppressed contractions by a median of 43.2% and 29.8%, respectively. The combination of atosiban plus fenoterol was measured at a level of 67.3% inhibition. There was no significant difference in the expected (63.2%) and observed inhibition effect of dual tocolysis (P=0.945).
Conclusion
This study demonstrated an additive effect of dual tocolysis of atosiban and fenoterol on human myometrium in vitro, but no synergistic or antagonistic effect.
Acknowledgments
The authors would like to thank Prof. Dr. Pharm. Ursula von Mandach for her support during the in vitro experiments and Alexandra Dolder for her precision in the laboratory. We also thank JoEllen Welter for her critical reading of the manuscript.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This study was financially supported by “Theodor und Ida Herzog-Egli Stiftung” and by “Anna Feddersen-Wagner-Fonds”.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet 2012;379:2162–72.10.1097/01.aoa.0000432360.25014.c3Search in Google Scholar
2. Lawn JE, Kerber K, Enweronu-Laryea C, Cousens S. 3.6 Million neonatal deaths – what is progressing and what is not? Semin Perinatol 2010;34:371–86.10.1053/j.semperi.2010.09.011Search in Google Scholar
3. Langhoff-Roos J, Kesmodel U, Jacobsson B, Rasmussen S, Vogel I. Spontaneous preterm delivery in primiparous women at low risk in Denmark: population based study. Br Med J 2006;332:937–9.10.1136/bmj.38751.524132.2FSearch in Google Scholar
4. Gyetvai K, Hannah ME, Hodnett ED, Ohlsson A. Tocolytics for preterm labor: a systematic review. Obstet Gynecol 1999;94: 869–77.10.1097/00006250-199911001-00043Search in Google Scholar
5. Caritis S. Adverse effects of tocolytic therapy. BJOG 2005;112(Suppl 1):74–8.10.1111/j.1471-0528.2005.00590.xSearch in Google Scholar
6. Doret M, Mellier G, Gaucherand P, Saade GR, Benchaib M, Frutoso J, et al. The in vitro effect of dual combinations of ritodrine, nicardipine and atosiban on contractility of pregnant rat myometrium. BJOG 2003;110:731–4.10.1111/j.1471-0528.2003.02443.xSearch in Google Scholar
7. Wachter R, Brenneisen R, Hamburger M, Mennet M, Schnelle M, Worel AM, et al. Leaf press juice from Bryophyllum pinnatum (Lamarck) Oken induces myometrial relaxation. Phytomedicine 2011;19:74–82.10.1016/j.phymed.2011.06.032Search in Google Scholar
8. Gwehenberger B, Rist L, Huch R, von Mandach U. Effect of Bryophyllum pinnatum versus fenoterol on uterine contractility. Eur J Obstet Gynecol Reprod Biol 2004;113:164–71.10.1016/S0301-2115(03)00370-1Search in Google Scholar
9. Goodwin TM, Valenzuela GJ, Silver H, Creasy G. Dose ranging study of the oxytocin antagonist atosiban in the treatment of preterm labor. Atosiban Study Group. Obstet Gynecol 1996;88:331–6.10.1016/0029-7844(96)00200-1Search in Google Scholar
10. von Mandach U, Boni R, Danko J, Huch R, Huch A. Pharmacokinetics of fenoterol in pregnant women. Arzneimittelforschung 1995;45:186–9.Search in Google Scholar
11. Kuc P, Laudanski P, Pierzynski P, Laudanski T. The effect of combined tocolysis on in vitro uterine contractility in preterm labour. Adv Med Sci 2011;56:88–94.10.2478/v10039-011-0019-xSearch in Google Scholar PubMed
12. Arrowsmith S, Neilson J, Wray S. The combination tocolytic effect of MgSO4 and an oxytocin receptor antagonist in myometrium from singleton and twin pregnancies. Am J Obstet Gynecol 2016;215:e1–9.10.1016/j.ajog.2016.08.015Search in Google Scholar
13. Buscher U, Chen FC, Riesenkampff E, von Dehn D, David M, Dudenhausen JW. Effects of oxytocin receptor antagonist atosiban on pregnant myometrium in vitro. Obstet Gynecol 2001;98:117–21.Search in Google Scholar
14. Carvajal JA, Zambrano MJ, Theodor NM, Moreno LE, Olguin TR, Vanhauwaert PS, et al. The synergic in vitro tocolytic effect of nifedipine plus ritodrine on human myometrial contractility. Reprod Sci 2017;24:635–40.10.1177/1933719116667221Search in Google Scholar
15. Romero R, Mazor M, Munoz H, Gomez R, Galasso M, Sherer DM. The preterm labor syndrome. Ann N Y Acad Sci 1994;734: 414–29.10.1111/j.1749-6632.1994.tb21771.xSearch in Google Scholar
16. Anotayanonth S, Subhedar NV, Garner P, Neilson JP, Harigopal S. Betamimetics for inhibiting preterm labour. Cochrane Database Syst Rev 2004;4:CD004352.10.1002/14651858.CD004352.pub2Search in Google Scholar
17. Goodwin TM, Valenzuela G, Silver H, Hayashi R, Creasy GW, Lane R. Treatment of preterm labor with the oxytocin antagonist atosiban. Am J Perinatol 1996;13:143–6.10.1055/s-2007-994312Search in Google Scholar
18. Vogel JP, Nardin JM, Dowswell T, West HM, Oladapo OT. Combination of tocolytic agents for inhibiting preterm labour. Cochrane Database Syst Rev 2014;7:Cd006169.10.1002/14651858.CD006169.pub2Search in Google Scholar
19. Ng QJ, Abdul Rahman MF, Lim ML, Chee JJ, Tan KH. Single versus combination tocolytic regimen in the prevention of preterm births in women: a prospective cohort study. J Perinat Med 2015;43:423–8.10.1515/jpm-2014-0216Search in Google Scholar
20. Gallagher LA, Gautieri RF. Influence of a combination of ritodrine and nifedipine on the isolated rat uterus. Res Commun Chem Pathol Pharmacol 1992;75:3–18.Search in Google Scholar
21. Saade GR, Taskin O, Belfort MA, Erturan B, Moise KJ Jr. In vitro comparison of four tocolytic agents, alone and in combination. Obstet Gynecol 1994;84:374–8.Search in Google Scholar
22. Doret M, Mellier G, Benchaib M, Piacenza JM, Gharib C, Pasquier JC. In vitro study of tocolytic effect of rofecoxib, a specific cyclo-oxygenase 2 inhibitor. Comparison and combination with other tocolytic agents. BJOG 2002;109:983–8.10.1111/j.1471-0528.2002.01518.xSearch in Google Scholar
23. Juni P, Nartey L, Reichenbach S, Sterchi R, Dieppe PA, Egger M. Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet 2004;364:2021–9.10.1016/S0140-6736(04)17514-4Search in Google Scholar
24. Rasmussen BB, Larsen LS, Senderovitz T. Pharmacokinetic interaction studies of atosiban with labetalol or betamethasone in healthy female volunteers. BJOG 2005;112:1492–9.10.1111/j.1471-0528.2005.00735.xSearch in Google Scholar PubMed
25. Yulia A, Johnson MR. Myometrial oxytocin receptor expression and intracellular pathways. Minerva Ginecol 2014;66: 267–80.Search in Google Scholar
©2019 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorial
- Ultrasound Doppler waveform assessment: the story continues
- Review
- Association between increased antenatal vaginal pH and preterm birth rate: a systematic review
- Mini Review
- Update on uterine tachysystole
- Research Articles – Obstetrics
- First trimester prediction of gestational diabetes mellitus using plasma biomarkers: a case-control study
- Emergency peripartal hysterectomy – a single-center analysis of the last 13 years at a tertiary perinatal care unit
- Efficacy and safety of misoprostol vaginal insert vs. oral misoprostol for induction of labor
- Vitamin A and β-carotene in pregnant and breastfeeding post-bariatric women in an urban population
- Effect of dual tocolysis with fenoterol and atosiban in human myometrium
- Antecedents of red cell transfusion in a large contemporary obstetric cohort
- Effect of n-3 long-chain polyunsaturated fatty acids supplementation in healthy mothers on DHA and EPA profiles in maternal and umbilical blood: a randomized controlled trial
- Research Articles – Fetus
- Effect of psychotropic drugs on fetal behavior in the third trimester of pregnancy
- Prognostic value of the aortic isthmus Doppler assessment on late onset fetal growth restriction
- Doppler evaluation of the fetal pulmonary artery pressure
- Mechanisms of death in structurally normal stillbirths
- The diagnostic value of a detailed first trimester anomaly scan in fetuses with increased nuchal translucency thickness
- Research Articles – Newborn
- Small for gestational age and extremely low birth weight infant outcomes
- Does heart rate variability improve prediction of failed extubation in preterm infants?
Articles in the same Issue
- Frontmatter
- Editorial
- Ultrasound Doppler waveform assessment: the story continues
- Review
- Association between increased antenatal vaginal pH and preterm birth rate: a systematic review
- Mini Review
- Update on uterine tachysystole
- Research Articles – Obstetrics
- First trimester prediction of gestational diabetes mellitus using plasma biomarkers: a case-control study
- Emergency peripartal hysterectomy – a single-center analysis of the last 13 years at a tertiary perinatal care unit
- Efficacy and safety of misoprostol vaginal insert vs. oral misoprostol for induction of labor
- Vitamin A and β-carotene in pregnant and breastfeeding post-bariatric women in an urban population
- Effect of dual tocolysis with fenoterol and atosiban in human myometrium
- Antecedents of red cell transfusion in a large contemporary obstetric cohort
- Effect of n-3 long-chain polyunsaturated fatty acids supplementation in healthy mothers on DHA and EPA profiles in maternal and umbilical blood: a randomized controlled trial
- Research Articles – Fetus
- Effect of psychotropic drugs on fetal behavior in the third trimester of pregnancy
- Prognostic value of the aortic isthmus Doppler assessment on late onset fetal growth restriction
- Doppler evaluation of the fetal pulmonary artery pressure
- Mechanisms of death in structurally normal stillbirths
- The diagnostic value of a detailed first trimester anomaly scan in fetuses with increased nuchal translucency thickness
- Research Articles – Newborn
- Small for gestational age and extremely low birth weight infant outcomes
- Does heart rate variability improve prediction of failed extubation in preterm infants?
