{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:43:28Z","timestamp":1790685808956,"version":"4.1.0"},"reference-count":47,"publisher":"American Physiological Society","issue":"4","funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["HL130231"],"award-info":[{"award-number":["HL130231"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2018,10,1]]},"abstract":"<jats:p> \u03b2-Adrenergic receptor (\u03b2-AR) activation produces the main positive inotropic response of the heart. During ischemia-reperfusion (I\/R), however, \u03b2-AR activation can trigger life-threatening arrhythmias. Because I\/R is frequently associated with oxidative stress, we investigated whether ryanodine receptor (RyR) oxidation contributes to proarrythmogenic Ca<jats:sup>2+<\/jats:sup> waves during \u03b2-AR activation. Measurements of contractile and electrical activity from Langendorff-perfused rabbit hearts revealed that I\/R produces tachyarrhythmias. Ventricular myocytes isolated from I\/R hearts had an increased level of oxidized glutathione (i.e., oxidative stress) and a decreased level of free thiols in RyRs (i.e., RyR oxidation). Furthermore, myocytes from I\/R hearts were characterized by increased sarcoplasmic reticulum (SR) Ca<jats:sup>2+<\/jats:sup> leak and enhanced fractional SR Ca<jats:sup>2+<\/jats:sup> release. In myocytes from nonischemic hearts, \u03b2-AR activation with isoproterenol (10 nM) produced only a positive inotropic effect, whereas in myocytes from ischemic hearts, isoproterenol at the same concentration triggered spontaneous Ca<jats:sup>2+<\/jats:sup> waves. \u03b2-AR activation produced a similar effect on RyR phosphorylation in control and I\/R myocytes. Treatment of myocytes from I\/R hearts with the reducing agent mercaptopropionylglycine (100 \u03bcM) attenuated RyR oxidization and decreased Ca<jats:sup>2+<\/jats:sup> wave frequency during \u03b2-AR activation. On the other hand, treatment of myocytes from nonischemic hearts with H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> (50 \u03bcM) increased SR Ca<jats:sup>2+<\/jats:sup> leak and triggered Ca<jats:sup>2+<\/jats:sup> waves during \u03b2-AR activation. Collectively, these results suggest that RyR oxidation after I\/R plays a critical role in the transition from positive inotropic to arrhythmogenic effects during \u03b2-AR stimulation. Prevention of RyR oxidation can be a promising strategy to inhibit arrhythmias and preserve positive inotropic effect of \u03b2-AR activation during myocardial infarction. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY Oxidative stress induced by ischemia plays a critical role in triggering arrhythmias during adrenergic stimulation. The combined increase in sarcoplasmic reticulum Ca<jats:sup>2+<\/jats:sup> leak (because of ryanodine receptor oxidation) and sarcoplasmic reticulum Ca<jats:sup>2+<\/jats:sup> load (because of adrenergic stimulation) can trigger proarrythmogenic Ca<jats:sup>2+<\/jats:sup> waves. Restoring normal ryanodine receptor redox status can be a promising strategy to prevent arrhythmias and preserve positive inotropic effect of adrenergic stimulation during myocardial infarction. <\/jats:p>","DOI":"10.1152\/ajpheart.00334.2018","type":"journal-article","created":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T11:08:33Z","timestamp":1532084913000},"page":"H1032-H1040","source":"Crossref","is-referenced-by-count":38,"title":["Oxidation of ryanodine receptor after ischemia-reperfusion increases propensity of Ca<sup>2+<\/sup> waves during \u03b2-adrenergic receptor stimulation"],"prefix":"10.1152","volume":"315","author":[{"given":"Elisa","family":"Bovo","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan R.","family":"Mazurek","sequence":"additional","affiliation":[{"name":"Department of 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