Relaxant effect of Levosimendan on human uterine contractility in vitro

Jun 15, 2010American journal of obstetrics and gynecology

Levosimendan's relaxing effect on human uterine muscle contractions in the lab

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Abstract

Levosimendan produced a 45.34% mean maximal inhibition of spontaneous uterine contractions in vitro.

Levosimendan inhibited both spontaneous and oxytocin-induced contractions of human uterine tissue.
The mean maximal inhibition for spontaneous contractions was 45.34% and for oxytocin-induced contractions was 41.88%.
Prior exposure to the K-ATP antagonist glibenclamide significantly reduced the inhibitory effect of levosimendan.
With glibenclamide, the mean maximal inhibition dropped to 19.04% for spontaneous contractions and 16.53% for oxytocin-induced contractions.
These results suggest levosimendan may influence uterine contractility through its effects on calcium sensitivity and potassium channels.

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OBJECTIVE: Levosimendan, a compound that exerts effects on calcium sensitivity and intracellular free calcium, in addition to opening ATP-sensitive K-channels, is widely used in the treatment of heart failure. Because of its dual mechanism of action, we hypothesized that it would modulate human uterine contractility.

STUDY DESIGN: Biopsies of human myometrium were obtained at elective cesarean section (n = 16). Dissected myometrial strips suspended under isometric conditions, undergoing spontaneous and oxytocin-induced contractions, were exposed to cumulative additions of levosimendan in the concentration range of 1 nmol/L to 100 mmol/L. In separate experiments, the effects of prior exposure to the K-ATP antagonist glibenclmide (100 mmol) on the effects of levosimendan on myometrial contractility were evaluated. Simultaneous controls were performed for all experiments.

RESULTS: Levosimendan exerted an inhibitory effect on spontaneous and agonist induced contractions, when compared with control strips. The mean maximal inhibition (MMI) values were as follows: 45.34% +/- 5.92% for spontaneous contractions (n = 6; P < .05), and 41.88% +/- 5.40% for oxytocin-induced contractions (n = 6; P < .05). The inhibitory effect of levosimendan was significantly antagonized by glibenclamide, resulting in the mean maximal inhibition for levosimendan reduced to 19.04% +/- 3.61% for spontaneous contractions (n = 6; P < .05), and 16.53% +/- 4.08% for oxytocin induced contractions (n = 6; P < .05).

CONCLUSION: Levosimendan exerted a potent relaxant effect on spontaneous and agonist-induced human uterine contractility in vitro. This effect was reduced in the presence of K-ATP blockade. Because of the putative role of levosimendan in inflammatory conditions, the findings here may have implications for its future use as therapy for preterm labor.

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Relaxant effect of Levosimendan on human uterine contractility in vitro

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