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Theriogenology2012; 78(3); 502-509; doi: 10.1016/j.theriogenology.2012.02.030

Ex vivo influence of carbetocin on equine myometrial muscles and comparison with oxytocin.

Abstract: To determine the intercyclic effect of oxytocin and carbetocin on equine myometrial tissue, the effect of the drugs was evaluated through pharmacokinetic and pharmacodynamic studies. The complete pharmacokinetic profile for oxytocin was unknown and had to be established. To do so, 25 IU of oxytocin were administered intravenously to six cycling mares and blood samples were collected before and 2, 4, 8, and 15 min after administration. The half-life of oxytocin was determined to be 5.89 min, the clearance rate 11.67 L/min, mean residence time (MRT) 7.78 min. The effective plasma concentration was estimated to be 0.25 ng/mL. This was similar to the concentration achieved for the organ bath study where the concentration that produced 50% of the maximum effect (EC(50)) was calculated at 0.45 ng/mL. To determine the intercyclic effect of oxytocin and carbetocin uterine myometrial samples were collected from slaughtered mares in estrus, diestrus, and anestrus. The samples were mounted in organ baths and exposed to four ascending, cumulative doses of oxytocin and carbetocin. Area under the curve and amplitude, maximum response (E(max)), and concentration that produced 50% of the maximum effect were studied for each agonist and statistically evaluated. The effect of oxytocin on equine myometrial tissue was higher during diestrus, and surprisingly anestrus, than during estrus, whereas the effect of carbetocin was the same independent of the stage of estrous cycle. A significant difference was found for estrous and anestrous samples when oxytocin was used but not when carbetocin was used.
Publication Date: 2012-04-24 PubMed ID: 22538009DOI: 10.1016/j.theriogenology.2012.02.030Google Scholar: Lookup
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  • Comparative Study
  • Journal Article

Summary

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The research article attempts to investigate the impact of oxytocin and carbetocin on the muscle tissue of a female equine uterus (myometrium) during different stages of the estrous cycle. It examines the pharmacokinetics of oxytocin and sees how oxytocin and carbetocin influence the myometrium in cycles of estrus, diestrus, and anestrus.

Methodology

The research team employed pharmacokinetic and pharmacodynamic studies to discern the effects of oxytocin and carbetocin on the myometrial tissue of horses. First, they had to establish a pharmacokinetic profile for oxytocin because none existed.

  • They did this by intravenously injecting 25 IU of oxytocin into six cycling female horses (mares).
  • Blood samples were collected at intervals of 0 (before injection), 2, 4, 8, and 15 minutes post-injection.
  • The half-life, clearance rates, and mean residence time of oxytocin were computed.

Results of the Pharmacokinetic Study

  • The half-life of oxytocin was determined to be approximately 5.89 minutes.
  • Oxytocin displayed a clearance rate of nearly 11.67L/min and a mean residence time (the average time the drug stays in the body) of roughly 7.78 minutes.
  • An effective plasma concentration of 0.25ng/mL was observed, further mirrored in the organ bath study, which recorded that 50% of the maximum effect was achieved at a concentration of 0.45ng/mL.

Post Pharmacokinetic Findings

The research team then analyzed the effects of oxytocin and carbetocin on myometrial tissue acquired from slaughtered mares in three different stages of the estrous cycle: estrus, diestrus, and anestrus.

  • The tissue samples were placed in organ baths and subjected to increasing doses of oxytocin and carbetocin.
  • The area under the curve and amplitude, maximum response, and concentration that delivered 50% of the maximum effect were studied for each hormone.
  • The results were then statistically evaluated.

Summary of the Findings

Researchers observed that:

  • The impact of oxytocin on equine myometrial tissue was higher during the diestrus and anestrus phases than during the estrus phase.
  • The effect of carbetocin remained consistent, regardless of the stage of the estrous cycle.
  • A significant difference was observed in the samples from the estrus and anestrus stages when oxytocin was applied, but there was no significant difference when carbetocin was employed.

This study provides insights into the intercyclic effects of the hormones oxytocin and carbetocin on equine myometrium, which could potentially assist in improving reproductive health management practices amongst equine populations.

Cite This Article

APA
Steckler D, Naidoo V, Gerber D, Kähn W. (2012). Ex vivo influence of carbetocin on equine myometrial muscles and comparison with oxytocin. Theriogenology, 78(3), 502-509. https://doi.org/10.1016/j.theriogenology.2012.02.030

Publication

ISSN: 1879-3231
NlmUniqueID: 0421510
Country: United States
Language: English
Volume: 78
Issue: 3
Pages: 502-509

Researcher Affiliations

Steckler, D
  • Section of Reproduction, Faculty of Veterinary Science, Onderstepoort, South Africa. daniela-steckler@gmx.de
Naidoo, V
    Gerber, D
      Kähn, W

        MeSH Terms

        • Anestrus / physiology
        • Animals
        • Diestrus / physiology
        • Estrus / physiology
        • Female
        • Half-Life
        • Horses / physiology
        • Injections, Intravenous / veterinary
        • Metabolic Clearance Rate
        • Myometrium / drug effects
        • Oxytocics / pharmacokinetics
        • Oxytocics / pharmacology
        • Oxytocin / administration & dosage
        • Oxytocin / analogs & derivatives
        • Oxytocin / pharmacokinetics
        • Oxytocin / pharmacology

        Citations

        This article has been cited 5 times.
        1. Tyrnenopoulou P, Fthenakis GC. Clinical Aspects of Bacterial Distribution and Antibiotic Resistance in the Reproductive System of Equids. Antibiotics (Basel) 2023 Mar 28;12(4).
          doi: 10.3390/antibiotics12040664pubmed: 37107026google scholar: lookup
        2. Marcet-Rius M, Bienboire-Frosini C, Lezama-García K, Domínguez-Oliva A, Olmos-Hernández A, Mora-Medina P, Hernández-Ávalos I, Casas-Alvarado A, Gazzano A. Clinical Experiences and Mechanism of Action with the Use of Oxytocin Injection at Parturition in Domestic Animals: Effect on the Myometrium and Fetuses. Animals (Basel) 2023 Feb 20;13(4).
          doi: 10.3390/ani13040768pubmed: 36830555google scholar: lookup
        3. Chen X, He Z, Li X, Song J, Huang M, Shi X, Li X, Li J, Xu G, Zheng J. Cuticle deposition duration in the uterus is correlated with eggshell cuticle quality in White Leghorn laying hens. Sci Rep 2021 Nov 11;11(1):22100.
          doi: 10.1038/s41598-021-01718-0pubmed: 34764400google scholar: lookup
        4. Elfers CT, Blevins JE, Lawson EA, Pittner R, Silva D, Kiselyov A, Roth CL. Robust Reductions of Body Weight and Food Intake by an Oxytocin Analog in Rats. Front Physiol 2021;12:726411.
          doi: 10.3389/fphys.2021.726411pubmed: 34646154google scholar: lookup
        5. Canisso IF, Segabinazzi LGTM, Fedorka CE. Persistent Breeding-Induced Endometritis in Mares - a Multifaceted Challenge: From Clinical Aspects to Immunopathogenesis and Pathobiology. Int J Mol Sci 2020 Feb 20;21(4).
          doi: 10.3390/ijms21041432pubmed: 32093296google scholar: lookup