{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:25:19Z","timestamp":1790933119068,"version":"4.1.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2001,5,29]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014As shown previously, exposure to NO donors initiates protective mechanisms in cardiomyocytes that persist after removal of the donor, a form of pharmacological preconditioning. Because NO also affects mitochondrial respiration, we studied the effect of NO on mitochondrial Ca\n            <jats:sup>2+<\/jats:sup>\n            uptake.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014Neonatal rat ventricular myocytes in primary culture were exposed to 1 hour of simulated ischemia and 1 hour of reoxygenation (sI\/R). Pretreatment with the NO donor\n            <jats:italic>S<\/jats:italic>\n            -nitroso-\n            <jats:italic>N<\/jats:italic>\n            -acetyl-penicillamine (SNAP) (1 mmol\/L for 90 minutes), followed by washing and incubation for 10 to 30 minutes, reduced sI\/R-induced cell death to 25.4% compared with control (propidium iodide exclusion assay,\n            <jats:italic>P<\/jats:italic>\n            &lt;0.001). Short (10-second) exposures to SNAP reversibly suppressed mitochondrial respiration without a detectable change in mitochondrial potential. In contrast, treatment with SNAP for 90 minutes caused a modest but sustained mitochondrial depolarization, as judged by JC-1 fluorescence. SNAP pretreatment limited cellular Ca\n            <jats:sup>2+<\/jats:sup>\n            overload during ischemia (fura-2 ratio rose to 226\u00b140% versus 516\u00b1170% of baseline, n=5,\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05) and prevented loss of cell membrane integrity during reoxygenation. SNAP pretreatment also significantly reduced the ability of mitochondria to accumulate Ca\n            <jats:sup>2+<\/jats:sup>\n            in the face of a similar cytosolic Ca\n            <jats:sup>2+<\/jats:sup>\n            load (peak rhod-2 fluorescence 133\u00b14% versus 166\u00b17% of baseline at similar fluo-3 levels,\n            <jats:italic>P<\/jats:italic>\n            =0.0004, n=52 and 25, respectively).\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014Pretreatment with an NO donor induces a modest, sustained mitochondrial depolarization and protects cardiomyocytes from sI\/R injury. The demonstrated reduction in mitochondrial Ca\n            <jats:sup>2+<\/jats:sup>\n            uptake possibly reduces cytosolic Ca\n            <jats:sup>2+<\/jats:sup>\n            overload, providing a likely mechanism for NO-induced protection.\n          <\/jats:p>","DOI":"10.1161\/01.cir.103.21.2617","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:09:32Z","timestamp":1339459772000},"page":"2617-2623","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":98,"title":["Mitochondria as Targets for Nitric Oxide\u2013Induced Protection During Simulated Ischemia and Reoxygenation in Isolated Neonatal Cardiomyocytes"],"prefix":"10.1161","volume":"103","author":[{"given":"Roby D.","family":"Rakhit","sequence":"first","affiliation":[{"name":"From the Departments of Cardiology, Kings College London, St Thomas\u2019 Hospital (R.D.R., M.S.M.), and Physiology, University College London (M.H.M., M.R.D.), UK. The first 2 authors contributed equally to this work."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mart H.","family":"Mojet","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology, Kings College London, St Thomas\u2019 Hospital (R.D.R., M.S.M.), and Physiology, University College London (M.H.M., M.R.D.), UK. The first 2 authors contributed equally to this work."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Marber","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology, Kings College London, St Thomas\u2019 Hospital (R.D.R., M.S.M.), and Physiology, University College London (M.H.M., M.R.D.), UK. The first 2 authors contributed equally to this work."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Duchen","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology, Kings College London, St Thomas\u2019 Hospital (R.D.R., M.S.M.), and Physiology, University College London (M.H.M., M.R.D.), UK. The first 2 authors contributed equally to this work."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.83.2.1991389"},{"key":"e_1_3_2_2_2","first-page":"417","volume":"67","year":"1972","unstructured":"Shen AC, Jennings RB. Myocardial calcium and magnesium in acute ischemic injury. 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