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The proposed teratogenic mechanism is blockade of the human ether\u2010\u00e1\u2010go\u2010go\u2010related (hERG)\/I<jats:sub>Kr<\/jats:sub>current in the embryonic heart causing bradycardia and arrhythmia resulting in altered cardiac blood flow and\/or embryonic hypoxia. To test this hypothesis, we examined the effect of three macrolide antibiotics on the function of the rat embryonic heart. Gestational day 13 rat embryos in vitro were exposed to erythromycin (25\u2013500\u00a0\u03bcM), clarithromycin (25\u2013500\u00a0\u03bcM), or azithromycin (100\u00a0\u03bcM to 1\u00a0mM) for 3 hr. The effect on the embryonic heart was monitored every hour. The results showed that erythromycin and clarithromycin caused a concentration\u2010dependent bradycardia. Twenty\u2010five micromolar was a no\u2010effect concentration for erythromycin and was close to a no\u2010effect concentration for clarithromycin. Azithromycin only caused significant bradycardia at 1\u00a0mM. Additional studies were performed with the embryos cultured at 40\u00b0C instead of 38\u00b0C, to mimic fever. The increased temperature increased the number of arrhythmias but did not worsen the drug\u2010induced bradycardia. The results support the concept that erythromycin and clarithromycin can adversely affect the embryonic heart but only at concentrations well outside expected embryonic exposure in the human<\/jats:p>","DOI":"10.1002\/bdrb.21107","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T21:33:38Z","timestamp":1397856818000},"page":"189-198","source":"Crossref","is-referenced-by-count":18,"title":["Effects of Macrolide Antibiotics on Rat Embryonic Heart Function In Vitro"],"prefix":"10.1002","volume":"101","author":[{"given":"Mats F.","family":"Nilsson","sequence":"first","affiliation":[{"name":"Drug Safety and Toxicology Department of Pharmaceutical Biosciences Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William S.","family":"Webster","sequence":"additional","affiliation":[{"name":"Drug Safety and Toxicology Department of Pharmaceutical Biosciences Uppsala University Uppsala Sweden"},{"name":"Department of Anatomy and Histology School of Medical Sciences University of Sydney Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,4,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.21003"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.20270"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/28.3.337"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2004.04.025"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2000.106556"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.60.12.1169"},{"issue":"1","key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7883\/yoken.65.1","article-title":"Chlamydial infections in term and preterm neonates","volume":"65","author":"Bekler C","year":"2012","journal-title":"Jpn J Infect Dis"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/sti.2006.022665"},{"key":"e_1_2_6_10_1","unstructured":"CDC.2010.Sexually transmitted diseases treatment guidelines 2010. 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