{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:48:38Z","timestamp":1791564518258,"version":"4.3.4"},"reference-count":77,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/15\/66\/31710, PG\/18\/49\/33833"],"award-info":[{"award-number":["PG\/15\/66\/31710, PG\/18\/49\/33833"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The cAMP analogue 8-Br-cAMP-AM (8-Br) confers marked protection against global ischaemia\/reperfusion of isolated perfused heart. We tested the hypothesis that 8-Br is also protective under clinically relevant conditions (regional ischaemia) when applied either before ischemia or at the beginning of reperfusion, and this effect is associated with the mitochondrial permeability transition pore (MPTP). 8-Br (10 \u03bcM) was administered to Langendorff-perfused rat hearts for 5 min either before or at the end of 30 min regional ischaemia. Ca2+-induced mitochondria swelling (a measure of MPTP opening) and binding of hexokinase II (HKII) to mitochondria were assessed following the drug treatment at preischaemia. Haemodynamic function and ventricular arrhythmias were monitored during ischaemia and 2 h reperfusion. Infarct size was evaluated at the end of reperfusion. 8-Br administered before ischaemia attenuated ventricular arrhythmias, improved haemodynamic function, and reduced infarct size during ischaemia\/reperfusion. Application of 8-Br at the end of ischaemia protected the heart during reperfusion. 8-Br promoted binding of HKII to the mitochondria and reduced Ca2+-induced mitochondria swelling. Thus, 8-Br protects the heart when administered before regional ischaemia or at the beginning of reperfusion. This effect is associated with inhibition of MPTP via binding of HKII to mitochondria, which may underlie the protective mechanism.<\/jats:p>","DOI":"10.3390\/cells10051223","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T12:19:57Z","timestamp":1621253997000},"page":"1223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Preconditioning or Postconditioning with 8-Br-cAMP-AM Protects the Heart against Regional Ischemia and Reperfusion: A Role for Mitochondrial Permeability Transition"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2278-5892","authenticated-orcid":false,"given":"Igor","family":"Khaliulin","sequence":"first","affiliation":[{"name":"Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Pharmacy Building, Ein Karem, Jerusalem 91120, Israel"},{"name":"Bristol Medical School (THS), Faculty of Health Sciences, University of Bristol, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimondo","family":"Ascione","sequence":"additional","affiliation":[{"name":"Bristol Medical School (THS), Faculty of Health Sciences, University of Bristol, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonid N.","family":"Maslov","sequence":"additional","affiliation":[{"name":"Cardiology Research Institute, Tomsk National Research Medical Center, The Russian Academy of Sciences, 111 a, Kievskaya Street, 634012 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8380-2054","authenticated-orcid":false,"given":"Haitham","family":"Amal","sequence":"additional","affiliation":[{"name":"Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Pharmacy Building, Ein Karem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6080-480X","authenticated-orcid":false,"given":"M. Saadeh","family":"Suleiman","sequence":"additional","affiliation":[{"name":"Bristol Medical School (THS), Faculty of Health Sciences, University of Bristol, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1172\/JCI62874","article-title":"Myocardial ischemia-reperfusion injury: A neglected therapeutic target","volume":"123","author":"Hausenloy","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1056\/NEJMoa0804626","article-title":"Percutaneous Coronary Intervention versus Coronary-Artery Bypass Grafting for Severe Coronary Artery Disease","volume":"360","author":"Serruys","year":"2009","journal-title":"N. Engl. J. 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