Hyponatraemia reversibly affects human myometrial contractility. An in vitro pilot study

BackgroundIn a previous study we found a significant correlation between dystocia and hyponatraemia that developed during labour. The present study examined a possible causal relationship. In vitro studies often use area under the curve (AUC) determined by frequency and force of contractions as a measure of myometrial contractility. However, a phase portrait plot of isometric contraction, obtained by plotting the first derivate of contraction against force of contraction, could indicate that bi-or multiphasic contractions might be less effective compared to the smooth contractions.Material and methodsMyometrial biopsies were obtained from 17 women undergoing elective caesarean section at term. Each biopsy was divided into 8 strips and mounted isometrically in a force transducer. Seven biopsies were used in the first part of the study when half of the strips were immersed in the hyponatraemic study solution S containing Na+ 120 mmol/L and observed for 1 hour, followed by 1 hour in normonatraemic control solution C containing Na+ 136 mmol/L, then again in S for 1 hour, and finally 1 hour in C. The other half of the strips were studied in reverse order, C-S-C-S. The remaining ten biopsies were included in the second part of the study. Response to increasing doses of oxytocin (OT) in solutions S and C was studied. In the first part of the study we calculated AUC, and created phase portrait plots of two different contractions from the same strip, one smooth and one biphasic. In both parts of the study we registered frequency and force of contractions, and described appearance of the contractions.ResultsFirst part of the study: Mean (median) contractions per hour in C: 8.7 (7.6), in S 14,3 (13). Mean (SD) difference between groups 5.6 (4.2), p = 0.018. Force of contractions in C: 11.8 (10.2) mN, in S: 10.8 (9.2) mN, p = 0.09, AUC increased in S; p = 0.018. Bi-/multiphasic contractions increased from 8% in C to 18% in S, p = 0.001. All changes were reversible in C. Second part of the study: Frequency after OT 1.65 x 10−9 M in C:3.4 (2.9), in S: 3.8 (3.2), difference between groups: p = 0.48. After OT 1.65 x 10−7 M in C: 7.8 (8.9), increase from previous OT administration: p = 0.09, in S: 8.7 (9.0), p = 0.04, difference between groups, p = 0.32. Only at the highest dose of OT dose was there an increase in force of contraction in S, p = 0.05, difference between groups, p = 0.33. Initial response to OT was more frequently bi/multiphasic in S, reaching significance at the highest dose of OT(1.65 x 10−7 M), p = 0.015. when almost all contractions were bi/multiphasic.ConclusionHyponatraemia reversibly increased frequency of contractions and appearance of bi-or multiphasic contractions, that could reduce myometrial contractility. This could explain the correlation of hyponatraemia and instrumental delivery previously observed. Contractions in the hyponatraemic solution more frequently showed initial multiphasic contractions when OT was added in increasing doses. Longer lasting labours carry the risk both of hyponatraemia and OT administration, and their negative interaction could be significant. Further studies should address this possibility.研究背景：既往研究发现，分娩期发生的低钠血症与难产之间存在显著相关性。本研究旨在探讨二者间可能存在的因果关系。体外研究常以宫缩频率与宫缩压力计算所得的曲线下面积（area under the curve, AUC）作为子宫肌收缩力的评价指标。不过，将宫缩的一阶导数与宫缩压力进行作图所得到的等长收缩相图，可提示双相或多相宫缩的收缩效果可能弱于平滑单相宫缩。材料与方法：本研究纳入17例足月择期剖宫产产妇，获取其子宫肌活检组织。每份活检组织均被切分为8条肌条，通过等长方式固定于张力换能器上。本研究第一部分使用7份活检组织：将半数肌条置于含钠离子浓度120 mmol/L的低钠血症研究溶液S中孵育1小时，随后换用含钠离子浓度136 mmol/L的正常钠浓度对照溶液C孵育1小时，再次更换为溶液S孵育1小时，最后更换为溶液C孵育1小时；剩余半数肌条则以相反顺序（C-S-C-S）进行孵育观测。剩余10份活检组织用于本研究第二部分，观察肌条在溶液S与溶液C中对递增剂量催产素（oxytocin, OT）的反应。第一部分研究中，我们计算了曲线下面积，并绘制了同一条肌条上两种不同宫缩（平滑单相宫缩与双相宫缩）的相图。两部分研究均记录宫缩频率与宫缩压力，并描述宫缩形态。研究结果：第一部分研究：对照组（溶液C）中每小时宫缩次数的均值（中位数）为8.7（7.6），低钠组（溶液S）为14.3（13）；组间均值差为5.6（标准差4.2），p=0.018。对照组宫缩压力均值为11.8（10.2）mN，低钠组为10.8（9.2）mN，p=0.09；低钠组曲线下面积显著升高，p=0.018。双相/多相宫缩占比从对照组的8%升至低钠组的18%，p=0.001。上述所有变化在更换为溶液C后均可逆转。第二部分研究：在1.65×10⁻⁹ M催产素处理后，对照组宫缩频率的均值（中位数）为3.4（2.9），低钠组为3.8（3.2），组间比较p=0.48。在1.65×10⁻⁷ M催产素处理后，对照组宫缩频率为7.8（8.9），较此前催产素给药后有所升高，p=0.09；低钠组为8.7（9.0），p=0.04，组间比较p=0.32。仅在最高剂量催产素处理时，低钠组宫缩压力出现显著升高，p=0.05，组间比较p=0.33。低钠组中，初始催产素应答更易表现为双相/多相宫缩，在最高剂量催产素（1.65×10⁻⁷ M）处理时差异具有统计学意义（p=0.015），此时几乎所有宫缩均为双相/多相宫缩。研究结论：低钠血症可可逆性升高宫缩频率，并增加双相/多相宫缩的发生比例，而这类宫缩可能会降低子宫肌收缩效能。这或可解释既往观察到的低钠血症与器械助产之间的相关性。在递增剂量催产素给药时，低钠溶液环境下的宫缩更易出现初始多相宫缩。产程延长同时存在低钠血症发生与催产素使用的风险，二者的负面交互作用可能具有临床意义，有待进一步研究验证。