PMID- 22127902
OWN - NLM
STAT- MEDLINE
DCOM- 20140519
LR  - 20161125
IS  - 1542-9741 (Electronic)
IS  - 1542-9733 (Linking)
VI  - 95
IP  - 1
DP  - 2012 Feb
TI  - Noninvasive high-resolution ultrasound reveals structural and functional deficits 
      in dimethadione-exposed fetal rat hearts in utero.
PG  - 35-46
LID - 10.1002/bdrb.20339 [doi]
AB  - BACKGROUND: We previously showed dimethadione (DMO), the N-demethylated 
      metabolite of the anticonvulsant trimethadione, induces ventricular septation 
      defects (VSD) and other heart anomalies in rat (Weston et al., 2011). Because of 
      the relationship between cardiac structure and function, we hypothesized that 
      DMO-induced structural defects of the heart are associated with in utero 
      functional deficits. To test the hypothesis, the goals were (1) define the 
      parameters for ultrasound in the rat conceptus, and; (2) use ultrasound to 
      identify structural and functional deficits following DMO treatment. METHODS: 
      Different ultrasound modes (B-mode, M-mode, and Pulse-wave Doppler) using four 
      high-resolution ultrasound transducer heads of varying frequency (25-40 MHz) were 
      tested on gestational day (GD) 14, 15, 16, 17, and 21. Having identified the 
      optimal conditions, pregnant Sprague-Dawley rats were administered six 300 mg/kg 
      doses of DMO every 12 hr beginning at 19:00 hr on GD 8 to generate conceptuses 
      with a high incidence of VSD. RESULTS: The three ultrasound modalities were used 
      to identify VSD and several novel and rare structural heart anomalies (cardiac 
      effusions and bifurcated septum) in live rat fetuses. DMO-treated hearts had an 
      array of functional deficits including a decrease in mean heart rate, ejection 
      fraction, and cardiac output and increased incidence of bradycardia and 
      dysrhythmia. CONCLUSIONS: The ultrasound biomicroscope is an effective tool for 
      the real-time characterization of the structure and function of embryo/fetal rat 
      hearts. DMO causes significant deficits to in utero heart function for up to ten 
      days (GD 21) following its final administration, suggesting long-term or possible 
      permanent changes cardiac function.
CI  - (c) 2011 Wiley-Liss, Inc.
FAU - Purssell, Elizabeth
AU  - Purssell E
AD  - Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, 
      Canada.
FAU - Weston, Andrea D
AU  - Weston AD
FAU - Thomson, Jason J
AU  - Thomson JJ
FAU - Swanson, Terri A
AU  - Swanson TA
FAU - Brown, Nigel A
AU  - Brown NA
FAU - Ozolins, Terence R S
AU  - Ozolins TR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111129
PL  - United States
TA  - Birth Defects Res B Dev Reprod Toxicol
JT  - Birth defects research. Part B, Developmental and reproductive toxicology
JID - 101155115
RN  - ALU9NPM703 (Dimethadione)
RN  - CYS9AKD70P (Isoflurane)
SB  - IM
MH  - Animals
MH  - Dimethadione/*adverse effects
MH  - Female
MH  - Fetus/*drug effects/*physiopathology
MH  - Heart/drug effects/*embryology/*physiopathology
MH  - Heart Function Tests
MH  - Heart Rate/drug effects
MH  - Heart Septal Defects, Ventricular/diagnostic imaging
MH  - Isoflurane/adverse effects
MH  - Myocardial Contraction/drug effects
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Ultrasonics
MH  - Ultrasonography
OTO - NOTNLM
OT  - cardiac defects
OT  - cardiac function
OT  - dimethadione
OT  - teratogens
OT  - ultrasound
OT  - ventricular septation defect
EDAT- 2011/12/01 06:00
MHDA- 2014/05/20 06:00
CRDT- 2011/12/01 06:00
PHST- 2011/07/21 00:00 [received]
PHST- 2011/09/09 00:00 [revised]
PHST- 2011/09/12 00:00 [accepted]
PHST- 2011/12/01 06:00 [entrez]
PHST- 2011/12/01 06:00 [pubmed]
PHST- 2014/05/20 06:00 [medline]
AID - 10.1002/bdrb.20339 [doi]
PST - ppublish
SO  - Birth Defects Res B Dev Reprod Toxicol. 2012 Feb;95(1):35-46. doi: 
      10.1002/bdrb.20339. Epub 2011 Nov 29.