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Theriogenology2016; 85(9); 1562-1567; doi: 10.1016/j.theriogenology.2016.01.009

The effect of isosorbide dinitrate on uterine and ovarian blood flow in cycling and early pregnant mares: A pilot study.

Abstract: Poor uterine perfusion has been proposed as a cause of infertility in mares. The objective of this study was to investigate the effect of isosorbide dinitrate (ISDN), a nitric oxide donor, on uterine and ovarian blood flow resistance during diestrus and early pregnancy in mares. Six Trotter mares, aged 7 to 14 years, were examined daily during the first 11 days of three diestrous periods, and five of those mares were also examined during the first 11 days of two pregnancies. Six mares randomly received a placebo, a low dose (30 mg, ISDN30), or a high dose of ISDN (60 mg, ISDN60) through three nonconsecutive cycles. The treatments were administered orally, every 12 hours from Day 1 to 11 of the cycle (Day 0 = ovulation). Five of the 6 mares received a placebo or 60 mg of ISDN orally every 12 hours from Day 1 to 11 of pregnancy. The mares were short cycled on Day 12 of each trial. Transrectal color Doppler was used to determine blood flow resistance semiquantitatively and expressed as pulsatility index. Mean pulsatility index of both uterine arteries combined and of the dominant (ipsilateral to the CL) ovarian artery was lower (treatment effects: P ≤ 0.01; time effects: P ≤ 0.002) in mares receiving 30 mg or 60 mg of ISDN compared with placebo-treated mares. Blood flow resistance in the dominant ovarian artery was lower in ISDN-treated pregnant mares than in placebo-treated pregnant and cycling mares (treatment effect: P = 0.04; time effect: P = 0.003). Isosorbide dinitrate increases uterine and ovarian perfusion in cycling mares and ovarian perfusion in early pregnant mares. Further studies are needed to investigate these effects in relation to fertility of the mare.
Publication Date: 2016-01-14 PubMed ID: 26879997DOI: 10.1016/j.theriogenology.2016.01.009Google Scholar: Lookup
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Summary

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This study investigates how isosorbide dinitrate (ISDN), a nitric oxide donor, affects ovarian and uterine blood flow in mares during diestrus and early pregnancy, with the findings suggesting that ISDN enhances blood flow, potentially influencing fertility.

About the Study

  • The main point of the research was to examine the impact of isosorbide dinitrate (ISDN) on the uterine and ovarian blood flow in mares during diestrus (a period of sexual inactivity between two periods of heat or estrus) and early pregnancy.
  • The study was prompted by the theory that inadequate uterine blood flow could be a cause of infertility in mares.
  • This pilot study was conducted on six Trotter mares, aged between seven and 14 years. Five of these mares were also observed during the initial days (11 days) of two pregnancies.

The Experiment

  • Every mare randomly received either a placebo, a low dosage (30mg), or a high dose (60mg) of ISDN across three non-consecutive cycles. The treatments were given orally every 12 hours, starting from the first day until the eleventh day of the cycle, with the zeroth day being the day of ovulation.
  • Five mares, out of the original six, were either given a placebo or a 60mg dose of ISDN orally during the same timings, but from the first day to the eleventh day of their pregnancy.
  • A technique known as transrectal color Doppler was utilized to semiquantitatively measure blood flow resistance, which was then expressed as a pulsatility index.

Findings

  • The results indicated that the mean pulsatility index of both integrated uterine arteries and the dominant ovarian artery (on the same side as the corpus luteum) was lower in mares that received either 30mg or 60mg ISDN compared to those that were treated with a placebo.
  • The blood flow resistance in the dominant ovarian artery was lower in pregnant mares treated with ISDN than in both placebo-treated pregnant mares and mares during diestrus.
  • In conclusion, the study found that ISDN increases uterine and ovarian blood flow in mares during diestrus and enhances ovarian perfusion in early pregnancy. The researchers believe these findings could potentially relate to the mare’s fertility, but further studies are needed for definitive conclusions.

Cite This Article

APA
Zoller D, Lüttgenau J, Steffen S, Bollwein H. (2016). The effect of isosorbide dinitrate on uterine and ovarian blood flow in cycling and early pregnant mares: A pilot study. Theriogenology, 85(9), 1562-1567. https://doi.org/10.1016/j.theriogenology.2016.01.009

Publication

ISSN: 1879-3231
NlmUniqueID: 0421510
Country: United States
Language: English
Volume: 85
Issue: 9
Pages: 1562-1567
PII: S0093-691X(16)00010-8

Researcher Affiliations

Zoller, D
  • Vetsuisse Faculty, Clinic of Reproductive Medicine, University of Zurich, Zurich, Switzerland. Electronic address: dzoller@vetclinics.uzh.ch.
Lüttgenau, J
  • Vetsuisse Faculty, Clinic of Reproductive Medicine, University of Zurich, Zurich, Switzerland.
Steffen, S
  • Vetsuisse Faculty, Clinic of Reproductive Medicine, University of Zurich, Zurich, Switzerland.
Bollwein, H
  • Vetsuisse Faculty, Clinic of Reproductive Medicine, University of Zurich, Zurich, Switzerland.

MeSH Terms

  • Animals
  • Blood Flow Velocity / drug effects
  • Female
  • Hemodynamics
  • Horses / physiology
  • Isosorbide Dinitrate / administration & dosage
  • Isosorbide Dinitrate / therapeutic use
  • Ovary / blood supply
  • Ovary / drug effects
  • Pilot Projects
  • Pregnancy
  • Uterus / blood supply
  • Uterus / drug effects
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / therapeutic use

Citations

This article has been cited 2 times.
  1. Hashem NM, El-Sherbiny HR, Fathi M, Abdelnaby EA. Nanodelivery System for Ovsynch Protocol Improves Ovarian Response, Ovarian Blood Flow Doppler Velocities, and Hormonal Profile of Goats.. Animals (Basel) 2022 Jun 3;12(11).
    doi: 10.3390/ani12111442pubmed: 35681906google scholar: lookup
  2. Islam W, Kimura S, Islam R, Harada A, Ono K, Fang J, Niidome T, Sawa T, Maeda H. EPR-Effect Enhancers Strongly Potentiate Tumor-Targeted Delivery of Nanomedicines to Advanced Cancers: Further Extension to Enhancement of the Therapeutic Effect.. J Pers Med 2021 May 28;11(6).
    doi: 10.3390/jpm11060487pubmed: 34071552google scholar: lookup