Relaxant effect of Levosimendan on human uterine contractility in vitro

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.