{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T14:18:58Z","timestamp":1773065938967,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2001,10,19]],"date-time":"2001-10-19T00:00:00Z","timestamp":1003449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Teratology"],"published-print":{"date-parts":[[2001,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>As a class effect, potent I<jats:sub>Kr<\/jats:sub>\u2010blockers have been shown to induce stage\u2010specific external malformations. The aim of this study was to investigate whether I<jats:sub>Kr<\/jats:sub>\u2010blockers also induce stage\u2010specific visceral and skeletal defects and to further elucidate a proposed arrhythmia\u2013hypoxia hypothesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Single oral doses of the selective I<jats:sub>Kr<\/jats:sub>\u2010blocker almokalant (ALM) 25\u2013150 \u03bcmol\/kg, 7\u201314 dams\/group, were given to Sprague\u2010Dawley rats on gestation days (GD) 10\u201314, and the fetuses were examined for malformations on GD 21. One group was pretreated with the spin\u2010trapping agent, \u03b1\u2010phenyl\u2010N\u2010t\u2010butylnitrone (PBN), given intraperitoneally 1 hr before ALM on GD 11.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cardiac ventricular septum defects and vascular malformations were observed after dosing on GD 10\u201311 and, to a lesser degree, on GD 12\u201313. Urogenital defects, absence\/malposition of the postcaval lung lobe, and attenuated diaphragm were observed mainly on GD 10\u201311. Skeletal examination showed a high incidence of vertebral abnormalities on thoracic level on GD 10, on lower thoracic to caudal level on GD 11, and sternebral defects were observed all days. On GD 13 brachy\u2010, oligo\u2010, and syndactyly of the forepaw were induced, and of the hindpaw on GD 14. PBN reduced the incidence of both visceral and skeletal defects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The stage specificity of observed visceral and skeletal defects correlates well with what has been reported in the literature after temporary interruption of oxygen supply during the same stages of development. The protective effect by PBN present further evidence that the teratogenicity of potent I<jats:sub>Kr<\/jats:sub>\u2010blockers is related to induction of hypoxia\u2013 reoxygenation injury due to embryonic cardiac arrhythmia. Teratology 64:292\u2013300, 2001. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/tera.1084","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T21:20:09Z","timestamp":1030310409000},"page":"292-300","source":"Crossref","is-referenced-by-count":32,"title":["Stage\u2010specific skeletal and visceral defects of the I<sub>Kr<\/sub>\u2010blocker almokalant: Further evidence for teratogenicity via a hypoxia\u2010related mechanism"],"prefix":"10.1002","volume":"64","author":[{"given":"Anna\u2010Carin","family":"Sk\u00f6ld","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Wellfelt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bengt R.","family":"Danielsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2001,11,26]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/28.3.337"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1026"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002040050139"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.1051270303"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.132.3419.89-a"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.73.5.857"},{"key":"e_1_2_1_8_1","first-page":"45","volume-title":"Developmental toxicology preclinical and clinical data in retrospect","author":"Danielsson BR","year":"1993"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-60447-8_4"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.78.1.15"},{"key":"e_1_2_1_11_1","unstructured":"DegenhardtK.1958.Analysis of intra\u2010uterine malformations of the vertebral column induced by oxygen deficiency in rabbits. 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