Effects of thrombin on myometrial contractions in vitro and in vivo

OBJECTIVE: A previous report from our laboratory demonstrated that thrombin stimulates myometrial contractions by activating the phosphatidylinositol signaling pathway in a dose-dependent fashion. The studies described in thi s report sought to determine whether thrombin and blood stimulate myometria l contractions both in vivo and in vitro and whether these uterotonic effec ts could be suppressed or prevented with thrombin inhibitors. STUDY DESIGN: In vitro contraction studies were performed with proestrus an d estrus rat myometrial tissue. In vivo contraction studies were performed with nonpregnant and timed-pregnant Sprague-Dawley rats. RESULTS: Pretreatment of thrombin with hirudin suppressed the uterotonic ef fects of thrombin in vitro. Fresh whole blood stimulated myometrial contrac tions in a dose-dependent fashion in vitro, and thrombin inhibitors decreas ed the myometrial response seen with blood alone. Thrombin increased the fr equency, intensity, and tone of myometrial contractions in vivo in a dose-r elated manner. In pregnant animals increasing doses of whole blood increase d the frequency and tone of myometrial contractions. In both pregnant and n onpregnant animals whole blood significantly stimulated myometrial contract ions, whereas heparinization of the blood significantly suppressed this in vivo uterotonic effect. CONCLUSION: Thrombin is a potent uterotonic agent both in vitro and in vivo ; furthermore, the uterotonic effects of blood appeared to be related to th rombin production during coagulation. These studies provide a possible mech anistic explanation for the observed increase in myometrial contractions in the presence of intrauterine bleeding and may also provide an insight into preterm labor associated with vaginal bleeding.