{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:08:38Z","timestamp":1792210118163,"version":"4.4.0"},"reference-count":64,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T00:00:00Z","timestamp":1581379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["PhD Fellowship"],"award-info":[{"award-number":["PhD Fellowship"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Ventricular arrhythmias are a major complication after myocardial infarction (MI), associated with sympathetic activation. The structurally heterogeneous peri\u2010infarct zone is a known substrate, but the functional role of the myocytes is less well known.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Recordings of monophasic action potentials <jats:italic>in vivo<\/jats:italic> reveal that the peri\u2010infarct zone is a source of delayed afterdepolarizations (DADs) and has a high beat\u2010to\u2010beat variability of repolarization (BVR) during adrenergic stimulation (isoproterenol, ISO).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Myocytes isolated from the peri\u2010infarct region have more DADs and spontaneous action potentials, with spontaneous Ca<jats:sup>2+<\/jats:sup> release, under ISO. These myocytes also have reduced repolarization reserve and increased BVR. Other properties of post\u2010MI remodelling are present in both peri\u2010infarct and remote myocytes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These data highlight the importance of altered myocyte adrenergic responses in the peri\u2010infarct region as source and substrate of post\u2010MI arrhythmias.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Ventricular arrhythmias are a major early complication after myocardial infarction (MI). The heterogeneous peri\u2010infarct zone forms a substrate for re\u2010entry while arrhythmia initiation is often associated with sympathetic activation. We studied the mechanisms triggering these post\u2010MI arrhythmias <jats:italic>in vivo<\/jats:italic> and their relation to regional myocyte remodelling. In pigs with chronic MI (6\u00a0weeks), <jats:italic>in vivo<\/jats:italic> monophasic action potentials were simultaneously recorded in the peri\u2010infarct and remote regions during adrenergic stimulation with isoproterenol (isoprenaline; ISO). Sham animals served as controls. During infusion of ISO <jats:italic>in vivo<\/jats:italic>, the incidence of delayed afterdepolarizations (DADs) and beat\u2010to\u2010beat variability of repolarization (BVR) was higher in the peri\u2010infarct than in the remote region. Myocytes isolated from the peri\u2010infarct region, in comparison to myocytes from the remote region, had more DADs, associated with spontaneous Ca<jats:sup>2+<\/jats:sup> release, and a higher incidence of spontaneous action potentials (APs) when exposed to ISO (9.99\u00a0\u00b1\u00a04.2 <jats:italic>vs<\/jats:italic>. 0.16\u00a0\u00b1\u00a00.05\u00a0APs\/min, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.004); these were suppressed by CaMKII inhibition. Peri\u2010infarct myocytes also had reduced repolarization reserve and increased BVR (26\u00a0\u00b1\u00a010\u00a0ms <jats:italic>vs<\/jats:italic>. 9\u00a0\u00b1\u00a07\u00a0ms, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), correlating with DAD activity. In contrast to these regional distinctions under ISO, alterations in Ca<jats:sup>2+<\/jats:sup> handling at baseline and myocyte hypertrophy were present throughout the left ventricle (LV). Expression of some of the related genes was, however, different between the regions. In conclusion, altered myocyte adrenergic responses in the peri\u2010infarct but not the remote region provide a source of triggered activity <jats:italic>in vivo<\/jats:italic> and of repolarization instability amplifying the substrate for re\u2010entry. These findings stimulate further exploration of region\u2010specific therapies targeting myocytes and autonomic modulation.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp278839","type":"journal-article","created":{"date-parts":[[2020,1,4]],"date-time":"2020-01-04T04:56:55Z","timestamp":1578113815000},"page":"2875-2895","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Altered adrenergic response in myocytes bordering a chronic myocardial infarction underlies <i>in vivo<\/i> triggered activity and repolarization instability"],"prefix":"10.1113","volume":"598","author":[{"given":"Eef","family":"Dries","sequence":"first","affiliation":[{"name":"Experimental Cardiology University of Leuven  Herestraat 49 box 911 Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Amoni","sequence":"additional","affiliation":[{"name":"Experimental Cardiology University of Leuven  Herestraat 49 box 911 Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8296-920X","authenticated-orcid":false,"given":"Bert","family":"Vandenberk","sequence":"additional","affiliation":[{"name":"Experimental Cardiology University of Leuven  Herestraat 49 box 911 Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7376-7101","authenticated-orcid":false,"given":"Daniel M.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Experimental Cardiology University of Leuven  Herestraat 49 box 911 Leuven Belgium"},{"name":"Institute of Cardiovascular Sciences University of Birmingham  Edgbaston Birmingham B15 2TT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Experimental Cardiology University of Leuven  Herestraat 49 box 911 Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandan K.","family":"Nagaraju","sequence":"additional","affiliation":[{"name":"Experimental Cardiology University of Leuven  Herestraat 49 box 911 Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Do\u00f1ate","family":"Puertas","sequence":"additional","affiliation":[{"name":"Experimental Cardiology University of Leuven  Herestraat 49 box 911 Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0010-3053","authenticated-orcid":false,"given":"Mouna","family":"Abdesselem","sequence":"additional","affiliation":[{"name":"Experimental Cardiology University of Leuven  Herestraat 49 box 911 Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demetrio J.","family":"Santiago","sequence":"additional","affiliation":[{"name":"Experimental Cardiology University of Leuven  Herestraat 49 box 911 Leuven Belgium"},{"name":"Laboratory of Molecular Cardiology Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)  C. 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