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The effects of nifedipine and ivabradine on the functionality of the early rat embryonic heart. Are these drugs a risk in early human pregnancy?
Author(s) -
Ritchie Helen E.,
Telenius Carolina,
Gustaffson Elin,
Webster William S.
Publication year - 2019
Publication title -
birth defects research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.845
H-Index - 17
ISSN - 2472-1727
DOI - 10.1002/bdr2.1457
Subject(s) - nifedipine , ivabradine , embryonic heart , bradycardia , heart rate , calcium channel blocker , medicine , asystole , endocrinology , anesthesia , calcium , embryonic stem cell , biology , blood pressure , biochemistry , gene
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 μM) caused asystole at high concentrations (8/10 embryos at 1.8 μM and 3/10 embryos at 0.9 μM) and markedly increased embryonic heart rate (EHR) in all surviving embryos but likely reduced blood flow due to weak contractions. Ivabradine (1.5 μM) 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.