Central hemodynamic effects of an oxytocin receptor antagonist (atosiban) in the isolated, perfused rat heart.
OBJECTIVE
Atosiban is a selective oxytocin receptor antagonist capable of inhibiting oxytocin-induced contractility of the uterus. Trials of this agent in intact animals and women as a tocolytic agent for preterm labor have shown atosiban to be devoid of cardiac effects. This is in contrast to other tocolytic agents, which have profound hemodynamic effects. We conducted this study to determine the cardiac effect of atosiban in the isolated, perfused rat heart model.


METHODS
Hearts were excised from 60 female Sprague-Dawley rats and attached to a Langendorff apparatus. Left ventricular systolic pressure, heart rate, and contractility were measured. Hearts from half of the animals were exposed serially to 300 micrograms/min, 600 micrograms/min, and 1200 micrograms/min of atosiban. The remaining hearts formed the control group and were exposed to aerated Krebs solution.


RESULTS
There were no significant differences between hearts exposed to atosiban and hearts within the control group for heart rate, left ventricular systolic pressure, and contractility. P values ranged from .12 to .73.


CONCLUSIONS
Using a classic physiologic model to study cardiac performance and drug effects, we were unable to detect any central hemodynamic effects of atosiban. This is in contrast to oxytocin, which we previously studied and found negative chronotropic and positive ionotropic effects.
Thorp
J M
JM
Department of OB/GYN, University of North Carolina, Chapel Hill 27599-7570, USA. thorp@med.unc.edu
Mayer
D
D
Kuller
J A
JA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors*; D015149:Tocolytic Agents / Q000494:pharmacology*; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000494:pharmacology; D017725:Ventricular Pressure / Q000187:drug effects
D018045:Receptors, Oxytocin; D015149:Tocolytic Agents; C047046:atosiban; D014668:Vasotocin