EFFECT OF METOPROLOL ON CHICK EMBRYONIC HEART FUNCTION AND DEVELOPMENT

Introduction:
Metoprolol is frequently used cardiovascular drug. With increasing average age of pregnant women we  face the need of drug treatment during pregnancy more frequently and the effect of beta 1 selective blocker metoprolol on human foetus is not clearly established yet. 
Methods:
ED4 and ED8 ex ovo chick embryos were studied using viodeomicroscopy and the ultrasound biomicroscopy with 40 MHz probe after intraamniotic injection of 200 µl (200 µg) of metoprolol or 200 µl of normal saline for a period of 30 minutes.
Embryotoxicity was  tested  in ovo after administration of various doses either metoprolol or normal saline between ED3-ED8. Wet and dry weight of embryo and embryonic heart was measured on day 9.
Results:

Acute effect. In ED4 embryos  the mean heart rate (MHR) decreased from 144 bpm to 98 bpm after metoprolol injection. In the control group the MHR of 156 bpm decreased to 146 bpm. In ED 8 embryos the  MHR decreased from 198 bpm to 15 bpm after metoprolol injection. The MHR in controls decreased from 185 bpm to 122 bpm . Cardiac arrhythmias were significantly more frequent in metoprolol group.
Embryotoxic  effect. No mortality was observed in embryos injected by lower doses of metoprolol or normal saline (2,20 µl). 17% mortality was documented in embryos injected by 200 µl(µg) compare to controls with mortality of 8%. No external anomalies or heart anomalies were noticed in metoprolol group. Wet and dry weight was not significantly different.
Conclusion:
ED8 embryos were more sensitive to negative chronotropic effect of metoprolol with significantly more frequent arrhythmias.  Minimal increase in embryolethality was noticed in high doses of metoprolol. According to our animal data metoprolol in usual doses appears to be relatively safe in pregnancy.