The influence of tocolytic drugs on cardiac function, large arteries, and resistance vessels

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.