PMID- 23845595
OWN - NLM
STAT- MEDLINE
DCOM- 20131126
LR  - 20141120
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 272
IP  - 2
DP  - 2013 Oct 15
TI  - Comparative effects of sodium channel blockers in short term rat whole embryo 
      culture.
PG  - 306-12
LID - S0041-008X(13)00296-2 [pii]
LID - 10.1016/j.taap.2013.06.023 [doi]
AB  - This study was undertaken to examine the effect on the rat embryonic heart of two 
      experimental drugs (AZA and AZB) which are known to block the sodium channel 
      Nav1.5, the hERG potassium channel and the l-type calcium channel. The sodium 
      channel blockers bupivacaine, lidocaine, and the l-type calcium channel blocker 
      nifedipine were used as reference substances. The experimental model was the 
      gestational day (GD) 13 rat embryo cultured in vitro. In this model the embryonic 
      heart activity can be directly observed, recorded and analyzed using computer 
      assisted image analysis as it responds to the addition of test drugs. The effect 
      on the heart was studied for a range of concentrations and for a duration up to 
      3h. The results showed that AZA and AZB caused a concentration-dependent 
      bradycardia of the embryonic heart and at high concentrations heart block. These 
      effects were reversible on washout. In terms of potency to cause bradycardia the 
      compounds were ranked AZB>bupivacaine>AZA>lidocaine>nifedipine. Comparison with 
      results from previous studies with more specific ion channel blockers suggests 
      that the primary effect of AZA and AZB was sodium channel blockage. The study 
      shows that the short-term rat whole embryo culture (WEC) is a suitable system to 
      detect substances hazardous to the embryonic heart.
CI  - (c) 2013.
FAU - Nilsson, Mats F
AU  - Nilsson MF
AD  - Department of Pharmaceutical Biosciences, Uppsala University, Sweden. Electronic 
      address: Mats.Nilsson@farmbio.uu.se.
FAU - Skold, Anna-Carin
AU  - Skold AC
FAU - Ericson, Ann-Christin
AU  - Ericson AC
FAU - Annas, Anita
AU  - Annas A
FAU - Villar, Rodrigo Palma
AU  - Villar RP
FAU - Cebers, Gvido
AU  - Cebers G
FAU - Hellmold, Heike
AU  - Hellmold H
FAU - Gustafson, Anne-Lee
AU  - Gustafson AL
FAU - Webster, William S
AU  - Webster WS
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20130708
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Drugs, Investigational)
RN  - 0 (NAV1.5 Voltage-Gated Sodium Channel)
RN  - 0 (Sodium Channel Blockers)
SB  - IM
MH  - Animals
MH  - Bradycardia/*chemically induced/embryology
MH  - Calcium Channel Blockers/administration & dosage/toxicity
MH  - Dose-Response Relationship, Drug
MH  - Drugs, Investigational/administration & dosage/*toxicity
MH  - Heart/*drug effects/*embryology
MH  - Heart Block/*chemically induced/embryology
MH  - Heart Rate/drug effects
MH  - Image Processing, Computer-Assisted
MH  - NAV1.5 Voltage-Gated Sodium Channel/metabolism
MH  - Organ Culture Techniques
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sodium Channel Blockers/administration & dosage/*toxicity
MH  - Time Factors
OTO - NOTNLM
OT  - Cardiac function
OT  - Drugs during pregnancy
OT  - Embryonic physiology
OT  - Hazard identification
OT  - Sodium channel blocker
EDAT- 2013/07/13 06:00
MHDA- 2013/12/16 06:00
CRDT- 2013/07/13 06:00
PHST- 2012/11/09 00:00 [received]
PHST- 2013/06/16 00:00 [revised]
PHST- 2013/06/21 00:00 [accepted]
PHST- 2013/07/13 06:00 [entrez]
PHST- 2013/07/13 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - S0041-008X(13)00296-2 [pii]
AID - 10.1016/j.taap.2013.06.023 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2013 Oct 15;272(2):306-12. doi: 
      10.1016/j.taap.2013.06.023. Epub 2013 Jul 8.