Anesth Pain Med.  2020 Oct;15(4):451-458. 10.17085/apm.20036.

Clinically relevant concentrations of dexmedetomidine may reduce oxytocin-induced myometrium contractions in pregnant rats

• Kim DJ
• Ki YJ
• Jang BH
• Kim S
• Kim SH
• Jung KT

• KMID: 2508407
• DOI: http://doi.org/10.17085/apm.20036

Abstract

Background
Recently, there have been some trials to use dexmedetomidine in the obstetric field but concerns regarding the drug include changes in uterine contractions after labor. We aimed to evaluate the effects of dexmedetomidine on the myometrial contractions of pregnant rats.
Methods
In a pilot study, the contraction of the myometrial strips of pregnant Sprague-Dawley rats in an organ bath with oxytocin at 1 mU/ml was assessed by adding dexmedetomidine from 10-6 to 10-2 M accumulatively every 20 min, and active tension and the number of contractions were evaluated. Then, changes in myometrial contractions were evaluated from high doses of dexmedetomidine (1.0 × 10−4 to 1.2 × 10−3 M). The effective concentrations (EC) for changes in uterine contractions were calculated using a probit model.
Results
Active tension and the number of contractions were significantly decreased at 10-3 M and 10-4 M dexmedetomidine, respectively (P < 0.05). A complete loss of contractions was seen at 10-2 M. Dexmedetomidine (1.0 × 10−4 to 1.2 × 10−3 M) decreased active tension and the number of contractions in a concentration-dependent manner. The EC95 of dexmedetomidine for inhibiting active tension and the number of contractions was 5.16 × 10-2 M and 2.55 × 10-5 M, respectively.
Conclusions
Active tension of the myometrium showed a significant decrease at concentrations of dexmedetomidine higher than 10-3 M. Thus, clinical concentrations of dexmedetomidine may inhibit uterine contractions. Further research is needed for the safe use of dexmedetomidine in the obstetrics field.

Keyword

Adrenergic alpha-agonists; Alpha 2 adrenergic receptors; Contraction; Dexmedetomidine; Rat; Relaxation; Smooth muscle; Uterus

Figure

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  Fig. 1. A pilot study on the changes in myometrial contractions caused by dexmedetomidine. There was no significant effect of dexmedetomidine concentrations from 10-6 to 10-5 M on myometrial contractions. Active tension and the number of contractions were significantly decreased by dexmedetomidine concentrations of 10-3 M and 10-4 M, respectively. Both active tension and the number of contractions disappeared at 10-2 M. The box plot represents active tension. Data are expressed as median (1Q, 3Q). The black dots represent the number of contractions. Data are expressed as mean. *P < 0.05 compared to the control active tension. †P < 0.05 compared to the control number of contractions.

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  Fig. 2. Probability of inhibiting active tension of the myometrium of a pregnant rat according to the concentration of dexmedetomidine (M). The horizontal bars represent the concentration of dexmedetomidine calculated to inhibit the active tension of myometrial stirps with 50% and 95% probabilities (EC50 and EC95), respectively, and a 95% confidence interval. EC: effective concentration.

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  Fig. 3. Probability of inhibiting the number of myometrial contractions of a pregnant rat according to the concentration of dexmedetomidine (M). The horizontal bars represent the concentration of dexmedetomidine calculated to inhibit the number of myometrial strip contractions with 50% and 95% probabilities (EC50 and EC95), respectively, and a 95% confidence interval. EC: effective concentration.

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