{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:01:26Z","timestamp":1791889286856,"version":"4.3.4"},"reference-count":41,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2009,11]]},"abstract":"<jats:p>\n                    Oxidative stress with hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) readily promotes early afterdepolarizations (EADs) and triggered activity (TA) in isolated rat and rabbit ventricular myocytes. Here we examined the effects of H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    on arrhythmias in intact Langendorff rat and rabbit hearts using dual-membrane voltage and intracellular calcium optical mapping and glass microelectrode recordings. Young adult rat (3\u20135 mo, N = 25) and rabbit (3\u20135 mo, N = 6) hearts exhibited no arrhythmias when perfused with H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    (0.1\u20132 mM) for up to 3 h. However, in 33 out of 35 (94%) aged (24\u201326 mo) rat hearts, 0.1 mM H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    caused EAD-mediated TA, leading to ventricular tachycardia (VT) and fibrillation (VF). Aged rabbits (life span, 8\u201312 yr) were not available, but 4 of 10 middle-aged rabbits (3\u20135 yr) developed EADs, TA, VT, and VF. These arrhythmias were suppressed by the reducing agent N-acetylcysteine (2 mM) and CaMKII inhibitor KN-93 (1 \u03bcM) but not by its inactive form (KN-92, 1 \u03bcM). There were no significant differences between action potential duration (APD) or APD restitution slope before or after H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    in aged or young adult rat hearts. In histological sections, however, trichrome staining revealed that aged rat hearts exhibited extensive fibrosis, ranging from 10\u201390%; middle-aged rabbit hearts had less fibrosis (5\u201335%), whereas young adult rat and rabbit hearts had &lt;4% fibrosis. In aged rat hearts, EADs and TA arose most frequently (70%) from the left ventricular base where fibrosis was intermediate (\u223c30%). Computer simulations in two-dimensional tissue incorporating variable degrees of fibrosis showed that intermediate (but not mild or severe) fibrosis promoted EADs and TA. We conclude that in aged ventricles exposed to oxidative stress, fibrosis facilitates the ability of cellular EADs to emerge and generate TA, VT, and VF at the tissue level.\n                  <\/jats:p>","DOI":"10.1152\/ajpheart.00579.2009","type":"journal-article","created":{"date-parts":[[2009,9,18]],"date-time":"2009-09-18T22:00:16Z","timestamp":1253311216000},"page":"H1594-H1605","source":"Crossref","is-referenced-by-count":114,"title":["Increased susceptibility of aged hearts to ventricular fibrillation during oxidative stress"],"prefix":"10.1152","volume":"297","author":[{"given":"Norishige","family":"Morita","sequence":"first","affiliation":[{"name":"Translational Arrhythmia Research Laboratory and Cardiovascular Research Laboratory, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali A.","family":"Sovari","sequence":"additional","affiliation":[{"name":"Translational Arrhythmia Research Laboratory and Cardiovascular Research Laboratory, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanfang","family":"Xie","sequence":"additional","affiliation":[{"name":"Translational Arrhythmia Research Laboratory and Cardiovascular Research Laboratory, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Fishbein","sequence":"additional","affiliation":[{"name":"Department of Pathology, David Geffen School of Medicine at the University of California, Los Angeles, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Mandel","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Cedars-Sinai Health System, David Geffen School of Medicine at University of California, Los Angeles, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Garfinkel","sequence":"additional","affiliation":[{"name":"Translational Arrhythmia Research Laboratory and Cardiovascular Research Laboratory, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shien-Fong","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, The Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng-Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, The Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai-Hua","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry New Jersey, Newark, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuhua","family":"Chen","sequence":"additional","affiliation":[{"name":"Translational Arrhythmia Research Laboratory and Cardiovascular Research Laboratory, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California, Los 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