PMID- 30653849
OWN - NLM
STAT- MEDLINE
DCOM- 20200106
LR  - 20200106
IS  - 2472-1727 (Electronic)
VI  - 111
IP  - 5
DP  - 2019 Mar 15
TI  - The effects of nifedipine and ivabradine on the functionality of the early rat 
      embryonic heart. Are these drugs a risk in early human pregnancy?
PG  - 281-288
LID - 10.1002/bdr2.1457 [doi]
AB  - BACKGROUND: When the human heart begins its earliest contractions from day 21, it 
      lacks a functional autonomic nerve supply. Instead, contractions are generated by 
      regular calcium transients later augmented by the funny current (I(f) ) produced 
      by sinoatrial-like cells. This study examined effects of blocking these currents 
      in the early rat embryonic heart. METHODS: Rat embryos were incubated in vitro 
      with either the calcium channel blocker nifedipine and/or the funny current (I(f) 
      ) blocker ivabradine for 1 hr to examine the effects of these drugs on the 
      activity of the embryonic heart. RESULTS: On gestational day (GD) 10, nifedipine 
      (0.45-1.8 muM) caused asystole at high concentrations (8/10 embryos at 1.8 muM and 
      3/10 embryos at 0.9 muM) and markedly increased embryonic heart rate (EHR) in all 
      surviving embryos but likely reduced blood flow due to weak contractions. 
      Ivabradine (1.5 muM) caused a 29% reduction in EHR in GD 10 embryos and a greater 
      than 50% reduction in EHR for GD 11-14 embryos. Combined exposure to both 
      nifedipine and ivabradine resulted in an additive effect. The increased EHR due 
      to nifedipine was reduced by the ivabradine. CONCLUSION: The results suggest that 
      exposure to nifedipine in human pregnancy 3-4 weeks postfertilization may cause a 
      direct effect on the embryonic heart resulting in reduced blood flow leading to 
      abnormal heart and/or blood vessel development and/or embryonic death. Accidental 
      exposure to ivabradine in the organogenic period would be expected to cause 
      embryonic bradycardia, hypoxia, malformations, and embryonic death. This drug is 
      currently contraindicated in pregnancy.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Ritchie, Helen E
AU  - Ritchie HE
AUID- ORCID: 0000-0001-9794-5702
AD  - Discipline of Biomedical Sciences, Sydney School of Medical Science, The 
      University of Sydney, Sydney, New South Wales, Australia.
FAU - Telenius, Carolina
AU  - Telenius C
AD  - Discipline of Anatomy and Histology, Sydney School of Medical Science, The 
      University of Sydney, Sydney, New South Wales, Australia.
FAU - Gustaffson, Elin
AU  - Gustaffson E
AD  - Discipline of Anatomy and Histology, Sydney School of Medical Science, The 
      University of Sydney, Sydney, New South Wales, Australia.
FAU - Webster, William S
AU  - Webster WS
AD  - Discipline of Anatomy and Histology, Sydney School of Medical Science, The 
      University of Sydney, Sydney, New South Wales, Australia.
LA  - eng
PT  - Journal Article
DEP - 20190117
PL  - United States
TA  - Birth Defects Res
JT  - Birth defects research
JID - 101701004
RN  - 3H48L0LPZQ (Ivabradine)
RN  - I9ZF7L6G2L (Nifedipine)
SB  - IM
MH  - Animals
MH  - Female
MH  - Heart/*drug effects/embryology
MH  - Heart Arrest/metabolism
MH  - Heart Rate/drug effects
MH  - Humans
MH  - Ivabradine/*adverse effects/pharmacology
MH  - Nifedipine/*adverse effects/pharmacology
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Risk Factors
OTO - NOTNLM
OT  - early pregnancy
OT  - embryonic death
OT  - embryonic heart rate
OT  - ivabradine
OT  - nifedipine
EDAT- 2019/01/18 06:00
MHDA- 2020/01/07 06:00
CRDT- 2019/01/18 06:00
PHST- 2018/10/30 00:00 [received]
PHST- 2018/12/10 00:00 [revised]
PHST- 2018/12/28 00:00 [accepted]
PHST- 2019/01/18 06:00 [pubmed]
PHST- 2020/01/07 06:00 [medline]
PHST- 2019/01/18 06:00 [entrez]
AID - 10.1002/bdr2.1457 [doi]
PST - ppublish
SO  - Birth Defects Res. 2019 Mar 15;111(5):281-288. doi: 10.1002/bdr2.1457. Epub 2019 
      Jan 17.