Heymans Institute of Pharmacology, Department of Clinical Pharmacology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
Eur J Clin Pharmacol. 2011 Jun;67(6):573-80. doi: 10.1007/s00228-011-1040-5. Epub 2011 Apr 15.
Beta-2 adrenoceptor agonistic drugs like ritodrine have been the reference tocolytic drugs, but are associated with cardiovascular side-effects. Atosiban, a newer drug, is a competitive antagonist of oxytocin and has been claimed to have fewer cardiovascular side effects. Until now, there has mainly been a subjective reporting of adverse reactions and few objective cardiovascular data. Evaluation of the acute effects of therapeutic doses of ritodrine and atosiban compared with placebo on cardiac function, large artery properties, blood pressure, and resistance vessels.
A double-blind, randomized trial was carried out in 20 non-pregnant female volunteers. Hemodynamic measurements were made under standardized conditions during kinetic steady state. Cardiac output was measured with echocardiography, large artery properties with an echo-tracking device. The effect on the microcirculation was estimated using the total peripheral resistance index (TPRI).
Atosiban did not differ from placebo. With ritodrine, cardiac function increased by 79% compared with placebo because of a rise in heart rate (91%). TPRI decreased by 48%. Ritodrine increased the distensibility of the common carotid artery by 62% and the compliance by 83%, independent of blood pressure. Compliance of the common femoral artery increased independently of pressure by 33% and the distensibility by 59%. Aortic pulse wave velocity was not influenced by either medication.
The present study shows potential beneficial vascular effects of ritodrine that are counterbalanced by the cardiac effects. Atosiban has no clinically relevant cardiovascular effects and may be a good alternative for ritodrine in pregnant women at risk of cardiovascular complications.
β-2 肾上腺素能激动剂药物，如利托君，一直是参考的保胎药物，但与心血管副作用相关。阿托西班是一种新型药物，是催产素的竞争性拮抗剂，据称其心血管副作用较少。到目前为止，主要是对不良反应进行主观报告，很少有客观的心血管数据。评价治疗剂量的利托君和阿托西班与安慰剂相比对心脏功能、大动脉特性、血压和阻力血管的急性影响。
在 20 名非妊娠女性志愿者中进行了一项双盲、随机试验。在动力学稳态下，在标准化条件下进行血流动力学测量。使用超声心动图测量心输出量，使用回声跟踪设备测量大动脉特性。使用总外周阻力指数（TPRI）估计微循环的影响。
阿托西班与安慰剂无差异。利托君使心脏功能增加 79%，与安慰剂相比，这是由于心率（91%）升高所致。TPRI 降低了 48%。利托君使颈总动脉的顺应性增加了 62%，弹性增加了 83%，与血压无关。股总动脉的顺应性独立于压力增加了 33%，弹性增加了 59%。两种药物均不影响主动脉脉搏波速度。
本研究显示利托君具有潜在的有益的血管作用，但被心脏作用所抵消。阿托西班对心血管无临床相关影响，可能是妊娠高危心血管并发症妇女利托君的良好替代药物。
