PMID- 24323366
OWN - NLM
STAT- MEDLINE
DCOM- 20141006
LR  - 20220409
IS  - 1542-9741 (Electronic)
IS  - 1542-9733 (Linking)
VI  - 98
IP  - 5
DP  - 2013 Oct
TI  - The effect on rat embryonic heart rate of Na+, K+, and Ca2+ channel blockers, and 
      the human teratogen phenytoin, changes with gestational age.
PG  - 416-27
LID - 10.1002/bdrb.21084 [doi]
AB  - In this study, we compared the effects of four ion channel blockers on rat 
      embryonic heart function during the organogenic period from gestational day (GD) 
      10 to 15, to determine the changes in dependence on ion channels during rat 
      cardiac development. Rat embryos in culture were exposed to either the human 
      ether-a-go-go-related gene potassium channel blocker, dofetilide (400 nM); the 
      sodium channel blocker, lidocaine (250 muM); the L-type calcium channel blocker, 
      nifedipine (1.8 muM); or the multichannel blocker, phenytoin (200 muM). Lidocaine 
      slowed the heart rate (HR) with the effect becoming more severe with increasing 
      GD. Dofetilide slowed the embryonic HR and caused arrhythmias with the most 
      severe effect on GD 11 to 13. Nifedipine primarily caused a negative inotropic 
      effect except on GD 10 when it stopped the heart in most embryos. Phenytoin 
      stopped the heart of most GD 10 to 12 embryos while on GD 13 to 15 phenytoin 
      slowed the heart. The results demonstrate that as the rat heart develops during 
      the organogenic period its functional dependence on ion channels changes 
      markedly. These changes are important for understanding drug effects on the 
      embryo during pregnancy and the methodology used provides a simple procedure for 
      assessing drug effects on the developing heart.
CI  - (c) 2013 Wiley Periodicals, Inc.
FAU - Nilsson, Mats F
AU  - Nilsson MF
AD  - Drug Safety and Toxicology, Department of Pharmaceutical Biosciences, Uppsala 
      University, Uppsala, Sweden.
FAU - Ritchie, Helen
AU  - Ritchie H
FAU - Webster, William S
AU  - Webster WS
LA  - eng
PT  - Journal Article
DEP - 20131209
PL  - United States
TA  - Birth Defects Res B Dev Reprod Toxicol
JT  - Birth defects research. Part B, Developmental and reproductive toxicology
JID - 101155115
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Phenethylamines)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Sodium Channel Blockers)
RN  - 0 (Sulfonamides)
RN  - 6158TKW0C5 (Phenytoin)
RN  - 98PI200987 (Lidocaine)
RN  - I9ZF7L6G2L (Nifedipine)
RN  - R4Z9X1N2ND (dofetilide)
SB  - IM
MH  - Animals
MH  - Calcium Channel Blockers/*toxicity
MH  - Female
MH  - Gestational Age
MH  - Heart Rate, Fetal/*drug effects
MH  - Lidocaine/toxicity
MH  - Nifedipine/toxicity
MH  - Phenethylamines/toxicity
MH  - Phenytoin/*toxicity
MH  - Potassium Channel Blockers/*toxicity
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sodium Channel Blockers/*toxicity
MH  - Sulfonamides/toxicity
OTO - NOTNLM
OT  - embryo/fetal physiology
OT  - in vitro screens
OT  - pharmaceuticals
OT  - teratogenicity
EDAT- 2013/12/11 06:00
MHDA- 2014/10/07 06:00
CRDT- 2013/12/11 06:00
PHST- 2013/09/05 00:00 [received]
PHST- 2013/10/28 00:00 [revised]
PHST- 2013/10/28 00:00 [accepted]
PHST- 2013/12/11 06:00 [entrez]
PHST- 2013/12/11 06:00 [pubmed]
PHST- 2014/10/07 06:00 [medline]
AID - 10.1002/bdrb.21084 [doi]
PST - ppublish
SO  - Birth Defects Res B Dev Reprod Toxicol. 2013 Oct;98(5):416-27. doi: 
      10.1002/bdrb.21084. Epub 2013 Dec 9.