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

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 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 mu M 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

Automated summary

This study investigated the effects of selected GBCAs on rat myometrial contractility and found that these contrast agents can modulate myometrial contractions at clinically relevant concentrations, potentially explaining the known side effects of these agents.