{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:43:23Z","timestamp":1767181403149,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1012244","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T00:00:00Z","timestamp":1720396800000}}],"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62133009"],"award-info":[{"award-number":["62133009"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Patients with myocardial ischemia and infarction are at increased risk of arrhythmias, which in turn, can exacerbate the overall risk of mortality. Despite the observed reduction in recurrent arrhythmias through antiarrhythmic drug therapy, the precise mechanisms underlying their effectiveness in treating ischemic heart disease remain unclear. Moreover, there is a lack of specialized drugs designed explicitly for the treatment of myocardial ischemic arrhythmia. This study employs an electrophysiological simulation approach to investigate the potential antiarrhythmic effects and underlying mechanisms of various pharmacological agents in the context of ischemia and myocardial infarction (MI). Based on physiological experimental data, computational models are developed to simulate the effects of a series of pharmacological agents (amiodarone, telmisartan, E-4031, chromanol 293B, and glibenclamide) on cellular electrophysiology and utilized to further evaluate their antiarrhythmic effectiveness during ischemia. On 2D and 3D tissues with multiple pathological conditions, the simulation results indicate that the antiarrhythmic effect of glibenclamide is primarily attributed to the suppression of efflux of potassium ion to facilitate the restitution of [K\n                    <jats:sup>+<\/jats:sup>\n                    ]\n                    <jats:sub>o<\/jats:sub>\n                    , as opposed to recovery of I\n                    <jats:sub>KATP<\/jats:sub>\n                    during myocardial ischemia. This discovery implies that, during acute cardiac ischemia, pro-arrhythmogenic alterations in cardiac tissue\u2019s excitability and conduction properties are more significantly influenced by electrophysiological changes in the depolarization rate, as opposed to variations in the action potential duration (APD). These findings offer specific insights into potentially effective targets for investigating ischemic arrhythmias, providing significant guidance for clinical interventions in acute coronary syndrome.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1012244","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T15:26:28Z","timestamp":1719329188000},"page":"e1012244","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["A simulation study on the antiarrhythmic mechanisms of established agents in myocardial ischemia and infarction"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3447-7352","authenticated-orcid":true,"given":"Qince","family":"Li","sequence":"first","affiliation":[]},{"given":"Zheng","family":"Yan","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1142-9435","authenticated-orcid":true,"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[]},{"given":"Cuiping","family":"Liang","sequence":"additional","affiliation":[]},{"given":"Xiqian","family":"Wang","sequence":"additional","affiliation":[]},{"given":"Xianghu","family":"Wu","sequence":"additional","affiliation":[]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[]},{"given":"Yongfeng","family":"Yuan","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1347-3491","authenticated-orcid":true,"given":"Kuanquan","family":"Wang","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2024,6,25]]},"reference":[{"issue":"2","key":"pcbi.1012244.ref001","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/cvr\/27.2.145","article-title":"Ischaemic myocardial injury and ventricular remodelling","volume":"27","author":"P Anversa","year":"1993","journal-title":"Cardiovasc Res"},{"issue":"4","key":"pcbi.1012244.ref002","doi-asserted-by":"crossref","first-page":"e1009388","DOI":"10.1371\/journal.pcbi.1009388","article-title":"Mechanisms of ventricular arrhythmias elicited by coexistence of multiple electrophysiological remodeling in ischemia: A simulation study","volume":"18","author":"C Liang","year":"2022","journal-title":"PLoS Comput Biol"},{"key":"pcbi.1012244.ref003","article-title":"Computational modeling of cardiac electrophysiology and arrhythmogenesis","author":"NA Trayanova","year":"2023","journal-title":"Physiol Rev"},{"key":"pcbi.1012244.ref004","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.pbiomolbio.2017.02.007","article-title":"Electrophysiological properties of computational human ventricular cell action potential models under acute ischemic conditions","volume":"129","author":"S Dutta","year":"2017","journal-title":"Prog Biophys Mol Biol"},{"issue":"11","key":"pcbi.1012244.ref005","doi-asserted-by":"crossref","first-page":"e1003891","DOI":"10.1371\/journal.pcbi.1003891","article-title":"Effect of global cardiac ischemia on human ventricular fibrillation: insights from a multi-scale mechanistic model of the human heart","volume":"10","author":"IV Kazbanov","year":"2014","journal-title":"PLoS Comput Biol"},{"issue":"1","key":"pcbi.1012244.ref006","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.pbiomolbio.2011.06.010","article-title":"Experiment-model interaction for analysis of epicardial activation during human ventricular fibrillation with global myocardial ischaemia","volume":"107","author":"RH Clayton","year":"2011","journal-title":"Prog Biophys Mol Biol"},{"issue":"2","key":"pcbi.1012244.ref007","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.cardiores.2004.01.033","article-title":"Acute ischemia-induced gap junctional uncoupling and arrhythmogenesis","volume":"62","author":"JR De Groot","year":"2004","journal-title":"Cardiovasc Res"},{"issue":"8","key":"pcbi.1012244.ref008","doi-asserted-by":"crossref","first-page":"e0160999","DOI":"10.1371\/journal.pone.0160999","article-title":"Comparison of Electric- and Magnetic-Cardiograms Produced by Myocardial Ischemia in Models of the Human Ventricle and Torso","volume":"11","author":"EA Alday","year":"2016","journal-title":"PLoS One"},{"issue":"10","key":"pcbi.1012244.ref009","doi-asserted-by":"crossref","first-page":"3051","DOI":"10.1161\/01.CIR.92.10.3051","article-title":"The Ib phase of ventricular arrhythmias in ischemic in situ porcine heart is related to changes in cell-to-cell electrical coupling. 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