Background
Despite concerns about safety, gadolinium‐based contrast agents (GBCAs) are still used for abdominal and pelvic imaging during pregnancy. Researchers have mainly focused on teratogenicity, while very little is known about their possible direct effects on uterine contractility, yet free gadolinium potentially impacts contractility through interaction with calcium channels.
Purpose
To investigate possible effects of selected GBCAs (namely gadoteridol, gadoversetamide, gadobutrol, gadoterate meglumine, and gadoxetic acid) on the contractility of rat myometrium.
Study Type
In vitro organ bath study.
Animal Model
Myometria were isolated from adult (10–12 weeks old) Sprague Dawley rats, both pregnant (N = 8) and nonpregnant (N = 36).
Field Strength/Sequence
NA.
Assessment
Myometrial strips were suspended in tissue bath containing physiological saline and isometric contractions were recorded. GBCAs were added to the tissue bath cumulatively, and their effects on contractility parameters (quantified by amplitude, frequency, and area under contractility curve [AUC]) were evaluated by 10‐minute intervals.
Statistical Tests
Normality data, checked by Shapiro–Wilk test, were transformed by arcsine when needed. One‐ or two‐way analysis of variance was performed, where appropriate, followed by Student–Newman–Keuls test. A P value of <0.05 was considered statistically significant.
Results
All of the assayed GBCAs elicited some alterations in the myometrial contractility in a concentration‐dependent manner. Gadoterate meglumine, gadoxetic acid, and gadoversetamide caused a concentration‐dependent significant attenuation in AUC (oxytocin‐induced, from 100% during control period to 45.1 ± 9.0% (nonpregnant) and 59.9 ± 8.5% (pregnant), for 90 μM gadoterate meglumine; respectively), and frequency of the spontaneous and oxytocin‐induced contractions. Gadobutrol and gadoteridol at highest dose significantly attenuated mean AUC and frequency of oxytocin‐induced contractions of nonpregnant myometrium.
Data Conclusion
Results from this in vitro study indicate that GBCAs elicit modulation of myometrial contractions at clinically relevant concentrations. These effects may account, at least partially, for the known potential side effects (rare cases of miscarriages and elective abortion) of these agents.
Level of Evidence
1
Technical Efficacy
Stage 5
Background/Aims: To determine whether spontaneous and stimulated contractile activity of myometrium in epileptic rats is different from healthy ones and whether anti-epileptic drugs (AEDs) have any direct influence on myometrial contractility.
Methods: Myometrial strips from nonpregnant and pregnant adult epileptic WAG/Rij and Wistar rats were suspended in organ bath containing physiological salt solution (37°C and pH 7.4, aerated with 95% oxygen-5% CO2), and isometric contractions were recorded. Effects of cumulative concentrations of selected AEDs including phenytoin, levetiracetam and valproic acid alone and in combination on oxytocin-induced contractions was examined.
Contractile parameters assessed included the area under curve (AUC), amplitude and frequency of contractions, evaluated by 10-minute periods. Data were analyzed using one-way ANOVA and Tukey HSD test.
Results: Spontaneous myometrial contractility and responses to oxytocin showed species difference. Compared with that of control Wistar rats, spontaneous contractions of myometrium from non-pregnant epileptic WAG/Rij rats was significantly higher and significantly lower in pregnant preparations. Upon stimulation with oxytocin WAG/Rij myometrium showed significantly lower contractile response compared with preparations from healthy control Wistars (p<0.01). Phenytoin and valproate caused concentration-dependent significant attenuation (P< 0.05) of spontaneous and oxytocin-induced contractions of myometrium from WAG/Rij and Wistar rats, both non-pregnant and pregnant.
Conclusion: Myometrial smooth muscle from epileptic rats showed different spontaneous and oxytocin-induced contractility and AEDs showed contractile modulatory actions, phenytoin being the most and levetiracetam the least effective. Although in vitro, our findings may be of clinical implications with regard to obstetric complications in epileptics and use of AEDs during pregnancy, and warrants further investigations.
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