Investigation of Effects of Gadolinium‐Based Contrast Agents on Uterine Contractility Using Isolated Rat Myometrium

Abstract

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

Bulk synthesis of conductive non-metallic carbon nanospheres and a 3D printed carrier device for scanning electron microscope calibration

“…The Shapiro-Wilk test was used to test the normality, whereas the homogeneity of variances were measured by the Levene's test. [31][32][33] Considering the small sample size, a residual plot was used to measure the feasibility of the model. Then, a two-way analysis of variance (ANOVA) was employed to analyze possible differences between the microsphere diameters under various accelerating voltages (15 kV, 20 kV and 25 kV) and magnications (8000×, 10 000×, 15 000× and 20 000×), which were selected as the independent variables.…”

Editorial for “Investigation of Effects ofGadolinium‐BasedContrast Agents on Uterine Contractility Using Isolated Rat Myometrium”

“…In this context, Dinç et al performed an extensive in vitro study on the effect of different GBCA on the myometrium of nonpregnant and pregnant rats. 6 Myometiral strips in Krebs solution, in the presence or absence of oxytocin, were exposed to either linear-ionic (gadotexic acid, gadoversetamide), macrocyclicionic (gadoterate meglumine), or macrocyclic-nonionic GBCA (gadoteridol, gadobutrol). Their contractions were investigated over time using an isometric force-displacement transducer.…”

“…In this context, the myometrium of the uterus is of high interest as contractions can cause significant discomfort and, during pregnancy, jeopardize the survival of the fetus. In this context, Dinç et al performed an extensive in vitro study on the effect of different GBCA on the myometrium of nonpregnant and pregnant rats 6 . Myometiral strips in Krebs solution, in the presence or absence of oxytocin, were exposed to either linear‐ionic (gadotexic acid, gadoversetamide), macrocyclic‐ionic (gadoterate meglumine), or macrocyclic‐nonionic GBCA (gadoteridol, gadobutrol).…”