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A Role for Adrenergic Receptors in the Uterotonic Effects of Ergometrine in Isolated Human TermNonlaboring Myometrium
背景与目的
麦角新碱是预防和处理产后出血的一种子宫收缩药。尽管麦角新碱被长期使用，但它的作用机制仍未被充分阐明。这项研究的目的是调查肾上腺素受体在麦角新碱作用于人类子宫肌层的机制中的作用。该研究调查了α-肾上腺素受体拮抗作用能逆转麦角新碱收缩子宫的假说。
方 法
获取择期剖宫产孕妇子宫肌层样品。然后将样品切成条并置于器官浴室中。麦角因子浓度 - 效应曲线（10-15至10-5 M）生成后，条状单独增加了麦角新碱的浓度（10-15至10-7M）和麦角新碱（10-7-10-5M），在酚妥拉明（10-7M），哌拉西定（10-7M），普萘洛尔（10-6M）和育亨宾（10-6M）中的出现。通过测量的振幅（g），频率（收缩/ 10min）和运动指数（g×收缩/ 10min）使用线性混合效应模型分析增加的麦角新碱的作用及药物联合的作用。
结 果
从33名产妇中获得样品并完成了157项实验。在麦角碱存在情况下，运动指数（增加0.342g×计数/ 10min /μM;95％置信区间[CI] 0.253-0.431，P <0.001），振幅（0.078 g /μM; 95％CI 0.0344-0.121，P = 5e-04）和频率（0.051计数/ 10分钟/μM; 95％CI 0.038-0.063，P <0.001）明显增加。 α-肾上腺素能拮抗剂酚妥拉明和更具选择性的α1-肾上腺素能拮抗剂哌唑嗪能够抑制麦角新碱介导的运动指数，幅度和频率（分别为-1.63 g×计数/ 10 min /μM和-16.70 g×计数/ 10min /μM）的增加。
结 论
这些结果为α-肾上腺素能信号机制在麦角碱对离体子宫平滑肌作用中的角色提供了新的证据。提示麦角碱的作用机制有助于进一步开发子宫收缩药。
原始文献摘要
Rebecca A. Fanning, MD, FCAI, MSc, Florike Sheehan, BSc,Claire Leyden, MSc,et al . A Role for Adrenergic Receptors in the Uterotonic Effects of Ergometrine in Isolated Human Term Nonlaboring Myometrium. Anesth Analg. 2017.3
BACKGROUND: postpartum hemorrhage. Despite its long-standing use, the mechanism by which it acts in humans has never been elucidated fully. The objective of this study was to investigate the role of adrenoreceptors in ergometrine’s mechanism of action in human myometrium. The study examined the hypothesis that α-adrenoreceptor antagonism would result in the reversal of the uterotonic effects of ergometrine.
METHODS: Myometrial samples were obtained from women undergoing elective cesarean delivery. The samples were then dissected into strips and mounted in organ bath chambers. After the generation of an ergometrine concentration–response curve (10–15 to 10–5 M), strips were treated with increasing concentrations of ergometrine (10–15 to 10–7 M) alone and ergometrine (10–7 to 10–5 M) in the presence of phentolamine (10–7 M), prazosin (10–7 M), propranolol (10–6M), or yohimbine (10–6 M). The effects of adding ergometrine and the effect of drug combinations were analyzed using linear mixed effects models with measures of amplitude (g), frequency (contractions/10 min), and motility index (g×contractions/10 min).
RESULTS:A total of 157 experiments were completed on samples obtained from 33 women.There was a significant increase in the motility index (adding 0.342 g × counts/10 min/μM;
95% confidence interval [CI] 0.253–0.431, P < .001), amplitude (0.078 g/μM; 95% CI 0.0344–0.121, P = 5e-04), and frequency (0.051 counts/10 min/μM; 95% CI 0.038–0.063, P < .001) in the presence of ergometrine. The α-adrenergic antagonist phentolamine and the more selectiveα1-adrenergic antagonist prazosin inhibited the ergometrine mediated increase in motility index, amplitude, and frequency (−1.63 g × counts/10 min/μM and −16.70 g × counts/10min/μM for motility index, respectively).
CONCLUSIONS: These results provide novel evidence for a role for α-adrenergic signaling mechanisms in the action of ergometrine on human myometrial smooth muscle in the in vitro setting.Information that sheds light on the mechanism of action of ergometrine may have implications for the development of further uterotonic agents.
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