{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T17:42:05Z","timestamp":1776793325130,"version":"3.51.2"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:00:00Z","timestamp":1674432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003793","name":"Hj\u00e4rt-Lungfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003793","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Repolarization prolongation can be the earliest electrophysiological change in ischemia, but its role in arrhythmogenesis is unclear. The aim of the present study was to evaluate the early ischemic action potential duration (APD) prolongation concerning its causes, expression in ECG and association with early ischemic ventricular fibrillation (phase 1A VF).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Coronary occlusion was induced in 18 anesthetized pigs, and standard 12 lead ECG along with epicardial electrograms were recorded. Local activation time (AT), end of repolarization time (RT), and activation-repolarization interval (ARIc) were determined as dV\/dt minimum during QRS-complex, dV\/dt maximum during T-wave, and rate-corrected RT\u2013AT differences, respectively. Patch-clamp studies were done in enzymatically isolated porcine cardiomyocytes. IK(ATP) activation and Ito1 inhibition were tested as possible causes of the APD change.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> During the initial period of ischemia, a total of 11 pigs demonstrated maximal ARIc prolongation &amp;gt;10\u00a0ms at 1 and\/or 2.5\u00a0min of occlusion (8 and 6 cases at 1 and 2.5\u00a0min, respectively) followed by typical ischemic ARIc shortening. The maximal ARIc across all leads was associated with VF development (OR 1.024 95% CI 1.003\u20131.046, <jats:italic>p<\/jats:italic> = 0.025) and maximal rate-corrected QT interval (QTc) (B 0.562 95% CI 0.346\u20130.775, <jats:italic>p<\/jats:italic> &amp;lt; 0.001) in logistic and linear regression analyses, respectively. Phase 1A VF incidence was associated with maximal QTc at the 2.5\u00a0min of occlusion in ROC curve analysis (AUC 0.867, <jats:italic>p<\/jats:italic> = 0.028) with optimal cut-off 456\u00a0ms (sensitivity 1.00, specificity 0.778). The pigs having maximal QTc at 2.5\u00a0min more and less than 450\u00a0ms significantly differed in phase 1A VF incidence in Kaplan-Meier analysis (log-rank <jats:italic>p<\/jats:italic> = 0.007). In the patch-clamp experiments, 4-aminopyridine did not produce any effects on the APD; however, pinacidil activated IK(ATP) and caused a biphasic change in the APD with initial prolongation and subsequent shortening.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The transiently prolonged repolarization during the initial period of acute ischemia was expressed in the prolongation of the maximal QTc interval in the body surface ECG and was associated with phase 1A VF. IK(ATP) activation in the isolated cardiomyocytes reproduced the biphasic repolarization dynamics observed <jats:italic>in vivo<\/jats:italic>, which suggests the probable role of IK(ATP) in early ischemic arrhythmogenesis.<\/jats:p>","DOI":"10.3389\/fphys.2023.1035032","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T06:25:14Z","timestamp":1674455114000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Prolonged repolarization in the early phase of ischemia is associated with ventricular fibrillation development in a porcine model"],"prefix":"10.3389","volume":"14","author":[{"given":"Olesya G.","family":"Bernikova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alena S.","family":"Tsvetkova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikhail A.","family":"Gonotkov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexey O.","family":"Ovechkin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina M.","family":"Demidova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan E.","family":"Azarov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pyotr G.","family":"Platonov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1016\/s0002-9149(99)00858-9","article-title":"Usefulness of the QTc interval in predicting myocardial ischemia in patients undergoing exercise stress testing","volume":"85","author":"Arab","year":"2000","journal-title":"Am. 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