{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T01:25:15Z","timestamp":1759541115727},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,11,29]],"date-time":"2011-11-29T00:00:00Z","timestamp":1322524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research Pt B"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>We previously showed dimethadione (DMO), the N\u2010demethylated 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\u2010induced 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Different ultrasound modes (B\u2010mode, M\u2010mode, and Pulse\u2010wave Doppler) using four high\u2010resolution ultrasound transducer heads of varying frequency (25\u201340 MHz) were tested on gestational day (GD) 14, 15, 16, 17, and 21. Having identified the optimal conditions, pregnant Sprague\u2013Dawley rats were administered six 300 mg\/kg doses of DMO every 12 hr beginning at 19:00hr on GD 8 to generate conceptuses with a high incidence of VSD.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>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\u2010treated 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>The ultrasound biomicroscope is an effective tool for the real\u2010time 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\u2010term or possible permanent changes cardiac function.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdrb.20339","type":"journal-article","created":{"date-parts":[[2011,12,1]],"date-time":"2011-12-01T11:23:41Z","timestamp":1322738621000},"page":"35-46","source":"Crossref","is-referenced-by-count":8,"title":["Noninvasive High\u2010Resolution Ultrasound Reveals Structural and Functional Deficits in Dimethadione\u2010Exposed Fetal Rat Hearts In Utero"],"prefix":"10.1002","volume":"95","author":[{"given":"Elizabeth","family":"Purssell","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Queen's University  Kingston Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea D.","family":"Weston","sequence":"additional","affiliation":[{"name":"Department of Developmental and Reproductive Toxicology Pfizer Research and Development  Eastern Point Road Groton Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason J.","family":"Thomson","sequence":"additional","affiliation":[{"name":"Department of Developmental and Reproductive Toxicology Pfizer Research and Development  Eastern Point Road Groton Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terri A.","family":"Swanson","sequence":"additional","affiliation":[{"name":"Pfizer Research and Development  Eastern Point Road Groton Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel A.","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences St. George's University of London  London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terence R.S.","family":"Ozolin\u0161","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Queen's University  Kingston Ontario Canada"},{"name":"Department of Developmental and Reproductive Toxicology Pfizer Research and Development  Eastern Point Road Groton Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,11,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2002.28999.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/euje.2000.0050"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420480403"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001362"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0300-483X(78)90040-9"},{"key":"e_1_2_6_7_1","first-page":"147","volume-title":"Developmental and Reproductive Toxicology\u2014A practical approach","author":"DeSesso J.","year":"2006"},{"key":"e_1_2_6_8_1","first-page":"257","article-title":"Successful closure of ventricular septal 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