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The effect of drugs with ion channel-blocking activity on the early embryonic rat heart.
Birth Defects Res B Dev Reprod Toxicol. 2010 Oct; 89(5):429-40.BD

Abstract

This study investigated the effects of a range of pharmaceutical drugs with ion channel-blocking activity on the heart of gestation day 13 rat embryos in vitro. The general hypothesis was that the blockade of the I(Kr)/hERG channel, that is highly important for the normal functioning of the embryonic rat heart, would cause bradycardia and arrhythmia. Concomitant blockade of other channels was expected to modify the effects of hERG blockade. Fourteen drugs with varying degrees of specificity and affinity toward potassium, sodium, and calcium channels were tested over a range of concentrations. The rat embryos were maintained for 2 hr in culture, 1 hr to acclimatize, and 1 hr to test the effect of the drug. All the drugs caused a concentration-dependent bradycardia except nifedipine, which primarily caused a negative inotropic effect eventually stopping the heart. A number of drugs induced arrhythmias and these appeared to be related to either sodium channel blockade, which resulted in a double atrial beat for each ventricular beat, or I(Kr)/hERG blockade, which caused irregular atrial and ventricular beats. However, it is difficult to make a precise prediction of the effect of a drug on the embryonic heart just by looking at the polypharmacological action on ion channels. The results indicate that the use of the tested drugs during pregnancy could potentially damage the embryo by causing periods of hypoxia. In general, the effects on the embryonic heart were only seen at concentrations greater than those likely to occur with normal therapeutic dosing.

Authors+Show Affiliations

Department of Anatomy and Histology, Sydney Medical School, University of Sydney, Sydney, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20973055

Citation

Abela, Dominique, et al. "The Effect of Drugs With Ion Channel-blocking Activity On the Early Embryonic Rat Heart." Birth Defects Research. Part B, Developmental and Reproductive Toxicology, vol. 89, no. 5, 2010, pp. 429-40.
Abela D, Ritchie H, Ababneh D, et al. The effect of drugs with ion channel-blocking activity on the early embryonic rat heart. Birth Defects Res B Dev Reprod Toxicol. 2010;89(5):429-40.
Abela, D., Ritchie, H., Ababneh, D., Gavin, C., Nilsson, M. F., Khan, M. K., Carlsson, K., & Webster, W. S. (2010). The effect of drugs with ion channel-blocking activity on the early embryonic rat heart. Birth Defects Research. Part B, Developmental and Reproductive Toxicology, 89(5), 429-40. https://doi.org/10.1002/bdrb.20270
Abela D, et al. The Effect of Drugs With Ion Channel-blocking Activity On the Early Embryonic Rat Heart. Birth Defects Res B Dev Reprod Toxicol. 2010;89(5):429-40. PubMed PMID: 20973055.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of drugs with ion channel-blocking activity on the early embryonic rat heart. AU - Abela,Dominique, AU - Ritchie,Helen, AU - Ababneh,Deena, AU - Gavin,Caroline, AU - Nilsson,Mats F, AU - Khan,Muhammad Khalid, AU - Carlsson,Kristin, AU - Webster,William S, PY - 2010/10/26/entrez PY - 2010/10/26/pubmed PY - 2011/2/11/medline SP - 429 EP - 40 JF - Birth defects research. Part B, Developmental and reproductive toxicology JO - Birth Defects Res. B Dev. Reprod. Toxicol. VL - 89 IS - 5 N2 - This study investigated the effects of a range of pharmaceutical drugs with ion channel-blocking activity on the heart of gestation day 13 rat embryos in vitro. The general hypothesis was that the blockade of the I(Kr)/hERG channel, that is highly important for the normal functioning of the embryonic rat heart, would cause bradycardia and arrhythmia. Concomitant blockade of other channels was expected to modify the effects of hERG blockade. Fourteen drugs with varying degrees of specificity and affinity toward potassium, sodium, and calcium channels were tested over a range of concentrations. The rat embryos were maintained for 2 hr in culture, 1 hr to acclimatize, and 1 hr to test the effect of the drug. All the drugs caused a concentration-dependent bradycardia except nifedipine, which primarily caused a negative inotropic effect eventually stopping the heart. A number of drugs induced arrhythmias and these appeared to be related to either sodium channel blockade, which resulted in a double atrial beat for each ventricular beat, or I(Kr)/hERG blockade, which caused irregular atrial and ventricular beats. However, it is difficult to make a precise prediction of the effect of a drug on the embryonic heart just by looking at the polypharmacological action on ion channels. The results indicate that the use of the tested drugs during pregnancy could potentially damage the embryo by causing periods of hypoxia. In general, the effects on the embryonic heart were only seen at concentrations greater than those likely to occur with normal therapeutic dosing. SN - 1542-9741 UR - https://www.unboundmedicine.com/medline/citation/20973055/The_effect_of_drugs_with_ion_channel_blocking_activity_on_the_early_embryonic_rat_heart_ L2 - https://doi.org/10.1002/bdrb.20270 DB - PRIME DP - Unbound Medicine ER -