{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T10:33:53Z","timestamp":1777718033156,"version":"3.51.4"},"reference-count":51,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T00:00:00Z","timestamp":1602806400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Toxicol"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction:<\/jats:title>\n                    <jats:p>Corrected QT (QTc) interval is an essential proarrhythmic risk biomarker, but recent data have identified limitations to its use. The J to T-peak (JTp) interval is an alternative biomarker for evaluating drug-induced proarrhythmic risk. The aim of this study was to evaluate pharmacological effects using spatial magnitude leads and DII electrocardiogram (ECG) leads and common ECG confounders (ie, stress and body temperature changes) on covariate adjusted QT (QTca), covariate adjusted JTp (JTpca), and covariate adjusted T-peak to T-end (Tpeca) intervals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Beagle dogs were exposed to body hyper- (42 \u00b0C) or hypothermic (33 \u00b0C) conditions or were administered epinephrine to assess confounding effects on heart rate corrected QTca, JTpca, and Tpeca intervals. Dofetilide (0.1, 0.3, 1.0 mg\/kg), ranolazine (100, 140, 200 mg\/kg), and verapamil (7, 15, 30, 43, 62.5 mg\/kg) were administered to evaluate pharmacological effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Covariate adjusted QT (slope \u221212.57 ms\/\u00b0C) and JTpca (\u221214.79 ms\/\u00b0C) were negatively correlated with body temperature but Tpeca was minimally affected. Epinephrine was associated with QTca and JTpca shortening, which could be related to undercorrection in the presence of tachycardia, while minimal effects were observed for Tpeca. There were no significant ECG change following ranolazine administration. Verapamil decreased QTca and JTpca intervals and increased Tpeca, whereas dofetilide increased QTca and JTpca intervals but had inconsistent effects on Tpeca.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Results highlight potential confounders on QTc interval, but also on JTpca and Tpeca intervals in nonclinical studies. These potential confounding effects may be relevant to the interpretation of ECG data obtained from nonclinical drug safety studies with Beagle dogs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1091581820954865","type":"journal-article","created":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T06:23:22Z","timestamp":1602829402000},"page":"530-541","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Confounders and Pharmacological Characterization When Using the QT, JTp, and Tpe Intervals in Beagle Dogs"],"prefix":"10.1177","volume":"39","author":[{"given":"Emmanuel","family":"Boulay","sequence":"first","affiliation":[{"name":"Charles River Laboratories, Laval, Quebec, Canada"},{"name":"Facult\u00e9 de m\u00e9decine v\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Troncy","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de m\u00e9decine v\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael V.","family":"Accardi","sequence":"additional","affiliation":[{"name":"Charles River Laboratories, Laval, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael K.","family":"Pugsley","sequence":"additional","affiliation":[{"name":"Toxicology, Cytokinetics, South San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Marie","family":"Downey","sequence":"additional","affiliation":[{"name":"Charles River Laboratories, Laval, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lois","family":"Miraucourt","sequence":"additional","affiliation":[{"name":"Charles River Laboratories, Laval, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai","family":"Huang","sequence":"additional","affiliation":[{"name":"Charles River Laboratories, Laval, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariane","family":"Menard","sequence":"additional","affiliation":[{"name":"Charles River Laboratories, Laval, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy","family":"Tan","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de m\u00e9decine v\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Dubuc-Mageau","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de m\u00e9decine v\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey","family":"Sanfacon","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de m\u00e9decine v\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mireille","family":"Guerrier","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de m\u00e9decine v\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8134-4558","authenticated-orcid":false,"given":"Simon","family":"Authier","sequence":"additional","affiliation":[{"name":"Charles River Laboratories, Laval, Quebec, Canada"},{"name":"Facult\u00e9 de m\u00e9decine v\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2020,10,16]]},"reference":[{"key":"bibr1-1091581820954865","unstructured":"Anon. Safety pharmacology studies for human pharmaceuticals S7A. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use; 2000. https:\/\/www.ich.org\/fileadmin\/Public_Web_Site\/ICH_Products\/Guidelines\/Safety\/S7A\/Step4\/S7A_Guideline.pdf."},{"key":"bibr2-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2014.155"},{"key":"bibr3-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1177\/1091581818813601"},{"key":"bibr4-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.112.973230"},{"key":"bibr5-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.111.962027"},{"key":"bibr6-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/eup376"},{"key":"bibr7-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2013.01.046"},{"key":"bibr8-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1038\/bjp.2008.265"},{"key":"bibr9-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1952.4.7.584"},{"key":"bibr10-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1016\/j.jelectrocard.2017.04.006"},{"key":"bibr11-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1542\/peds.101.6.1053"},{"key":"bibr12-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1016\/j.ihj.2013.12.021"},{"key":"bibr13-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-7176.2011.00513.x"},{"key":"bibr14-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.03.019"},{"key":"bibr15-1091581820954865","unstructured":"Guide to the Care and Use of Experimental Animals Volume 1. 2nd ed; 2017:209."},{"key":"bibr16-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(60)90360-X"},{"key":"bibr17-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/45.2.247"},{"key":"bibr18-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1007\/BF01691254"},{"key":"bibr19-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.324.7349.1320"},{"key":"bibr20-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1016\/j.jelectrocard.2013.05.139"},{"key":"bibr21-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1980.03300400005002"},{"key":"bibr22-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/95.12.775"},{"key":"bibr23-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1993.sp019761"},{"key":"bibr24-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM194102132240705"},{"key":"bibr25-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.7.2.210"},{"key":"bibr26-1091581820954865","doi-asserted-by":"publisher","DOI":"10.7812\/TPP\/12-088"},{"key":"bibr27-1091581820954865","doi-asserted-by":"crossref","unstructured":"Darbar D, Smith M, M\u00f6rike K, et al. Epinephrine-induced changes in serum potassium and cardiac repolarization and effects of pretreatment with propranolol and diltiazem. Am J Cardiol. 1996;77(15):1351\u20131355. doi: https:\/\/doi.org\/10.1016\/S0002-9149(96)00204-4.","DOI":"10.1016\/S0002-9149(96)00204-4"},{"key":"bibr28-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.49.1.90"},{"key":"bibr29-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)02850-4"},{"key":"bibr30-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.600445"},{"key":"bibr31-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.2.753"},{"key":"bibr32-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.22.8756"},{"key":"bibr33-1091581820954865","unstructured":"Iqubal A. Clinical Updates on Drug-Induced Cardiotoxicity; 2018:16\u201326."},{"key":"bibr34-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.310083"},{"key":"bibr35-1091581820954865","doi-asserted-by":"publisher","DOI":"10.2131\/jts.30.229"},{"key":"bibr36-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1111\/j.1542-474X.1997.tb00325.x"},{"key":"bibr37-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1177\/0091270011409234"},{"key":"bibr38-1091581820954865","doi-asserted-by":"crossref","unstructured":"Magnano AR, Holleran S, Ramakrishnan R, et al. Autonomic nervous system influences on QT interval in normal subjects. J Am Coll Cardiol. 2002;39(11):1820\u20131826. doi: https:\/\/doi.org\/10.1016\/S0735-1097(02)01852-1.","DOI":"10.1016\/S0735-1097(02)01852-1"},{"key":"bibr39-1091581820954865","doi-asserted-by":"crossref","unstructured":"Fozzard HA. After Depolarizations and Triggered Activity, 1992:05\u2013113. Steinkopff.","DOI":"10.1007\/978-3-642-72477-0_10"},{"key":"bibr40-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.23.2851"},{"key":"bibr41-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2005.01590.x"},{"key":"bibr42-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1097\/00001573-200201000-00007"},{"key":"bibr43-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4637.2012.01406.x"},{"key":"bibr44-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705879"},{"key":"bibr45-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.84.9.989"},{"key":"bibr46-1091581820954865","first-page":"137","volume":"1","author":"Sintra Grilo L","year":"2010","journal-title":"Front Pharmacol"},{"key":"bibr47-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199710000-00013"},{"key":"bibr48-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2018.04.004"},{"key":"bibr49-1091581820954865","first-page":"677","volume":"2012","author":"Guldenring D","year":"2012","journal-title":"Conf Proc IEEE Eng Med Biol Soc"},{"key":"bibr50-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1186\/1475-925X-11-16"},{"key":"bibr51-1091581820954865","doi-asserted-by":"publisher","DOI":"10.1002\/clc.14"}],"container-title":["International Journal of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1091581820954865","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1091581820954865","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1091581820954865","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:24:04Z","timestamp":1777458244000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1091581820954865"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,16]]},"references-count":51,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1177\/1091581820954865"],"URL":"https:\/\/doi.org\/10.1177\/1091581820954865","relation":{},"ISSN":["1091-5818","1092-874X"],"issn-type":[{"value":"1091-5818","type":"print"},{"value":"1092-874X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,16]]}}}