{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T15:18:58Z","timestamp":1776352738682,"version":"3.51.2"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T00:00:00Z","timestamp":1718928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T00:00:00Z","timestamp":1718928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004621","name":"Kerman University of Medical Sciences","doi-asserted-by":"publisher","award":["98000870"],"award-info":[{"award-number":["98000870"]}],"id":[{"id":"10.13039\/501100004621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004621","name":"Kerman University of Medical Sciences","doi-asserted-by":"publisher","award":["98000870"],"award-info":[{"award-number":["98000870"]}],"id":[{"id":"10.13039\/501100004621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004621","name":"Kerman University of Medical Sciences","doi-asserted-by":"publisher","award":["98000870"],"award-info":[{"award-number":["98000870"]}],"id":[{"id":"10.13039\/501100004621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004621","name":"Kerman University of Medical Sciences","doi-asserted-by":"publisher","award":["98000870"],"award-info":[{"award-number":["98000870"]}],"id":[{"id":"10.13039\/501100004621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cardiac ischemic preconditioning (Pre) reduces cardiac ischemia\u2013reperfusion injury (IRI) by stimulating opioid receptors. Chronic use of opioids can alter the signaling pathways. We investigated the effects of chronic methadone use on IRI and Pre. The experiments were performed on isolated hearts of male Wistar rats in four groups: IRI, Methadone\u2009+\u2009IRI (M-IRI), Pre\u2009+\u2009IRI (Pre-IRI), Methadone\u2009+\u2009Pre\u2009+\u2009IRI (M-Pre-IRI). The infarct size (IS) in the Pre-IRI group was smaller than the IRI group (26.8% vs. 47.8%, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). In the M-IRI and M-Pre-IRI groups, the infarct size was similar to the IRI group. Akt (Ak strain transforming) phosphorylation in the Pre-IRI, M-IRI, and M-Pre-IRI groups was significantly higher than in the IRI group (0.56\u2009\u00b1\u20090.15, 0.63\u2009\u00b1\u20090.20, and 0.93\u2009\u00b1\u20090.18 vs 0.28\u2009\u00b1\u20090.17 respectively). STAT3 (signal transducer and activator of transcription 3) phosphorylation in the Pre-IRI and M-Pre-IRI groups (1.38\u2009\u00b1\u20090.14 and 1.46\u2009\u00b1\u20090.33) was significantly higher than the IRI and M-IRI groups (0.99\u2009\u00b1\u20090.1 and 0.98\u2009\u00b1\u20090.2). Thus, chronic use of methadone not only has no protective effect against IRI but also destroys the protective effects of ischemic preconditioning. This may be due to the hyperactivation of Akt and changes in signaling pathways.<\/jats:p>","DOI":"10.1038\/s41598-024-65349-x","type":"journal-article","created":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T16:04:20Z","timestamp":1718985860000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Inhibition of the protective effects of preconditioning in ischemia\u2013reperfusion injury by chronic methadone: the role of pAkt and pSTAT3"],"prefix":"10.1038","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7148-5568","authenticated-orcid":false,"given":"Mahboobeh","family":"Yeganeh-Hajahmadi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0913-9450","authenticated-orcid":false,"given":"Zeinab","family":"Kordestani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9062-4823","authenticated-orcid":false,"given":"Yasmin","family":"Moosavi-Saeed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7879-9938","authenticated-orcid":false,"given":"Farzaneh","family":"Rostamzadeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,6,21]]},"reference":[{"key":"65349_CR1","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.phrs.2014.08.004","volume":"89","author":"AJ Perricone","year":"2014","unstructured":"Perricone, A. J. & Vander Heide, R. S. Novel therapeutic strategies for ischemic heart disease. Pharmacol. Res. 89, 36\u201345 (2014).","journal-title":"Pharmacol. Res."},{"key":"65349_CR2","first-page":"93","volume":"2","author":"JW Kennedy","year":"1993","unstructured":"Kennedy, J. W. Limiting the size of myocardial infarction by early coronary artery reperfusion. Heart Dis. Stroke 2, 93\u201397 (1993).","journal-title":"Heart Dis. Stroke"},{"key":"65349_CR3","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1161\/CIRCRESAHA.113.300765","volume":"113","author":"RS Vander Heide","year":"2013","unstructured":"Vander Heide, R. S. & Steenbergen, C. Cardioprotection and myocardial reperfusion: Pitfalls to clinical application. Circ. Res. 113, 464\u2013477 (2013).","journal-title":"Circ. Res."},{"key":"65349_CR4","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1002\/cphy.c160006","volume":"1","author":"T Kalogeris","year":"2016","unstructured":"Kalogeris, T., Baines, C. P., Krenz, M. & Korthuis, R. J. Ischemia\/reperfusion. Compr. Physiol. 1, 113\u2013170 (2016).","journal-title":"Compr. Physiol."},{"key":"65349_CR5","doi-asserted-by":"publisher","first-page":"159","DOI":"10.3390\/jcm13010159","volume":"13","author":"M Buske","year":"2023","unstructured":"Buske, M. et al. Reperfusion injury: How can we reduce it by pre-, per-, and postconditioning. J. Clin. Med. 13, 159 (2023).","journal-title":"J. Clin. Med."},{"key":"65349_CR6","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1161\/01.CIR.74.5.1124","volume":"74","author":"CE Murry","year":"1986","unstructured":"Murry, C. E., Jennings, R. B. & Reimer, K. A. Preconditioning with ischemia: A delay of lethal cell injury in ischemic myocardium. Circulation 74, 1124\u20131136 (1986).","journal-title":"Circulation"},{"key":"65349_CR7","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1093\/cvr\/cvy286","volume":"115","author":"DJ Hausenloy","year":"2019","unstructured":"Hausenloy, D. J. et al. The coronary circulation in acute myocardial ischaemia\/reperfusion injury: A target for cardioprotection. Cardiovasc. Res. 115, 1143\u20131155 (2019).","journal-title":"Cardiovasc. Res."},{"key":"65349_CR8","doi-asserted-by":"publisher","first-page":"H1603","DOI":"10.1152\/ajpheart.00963.2003","volume":"286","author":"ML Riess","year":"2004","unstructured":"Riess, M. L., Stowe, D. F. & Warltier, D. C. Cardiac pharmacological preconditioning with volatile anesthetics: From bench to bedside?. Am. J. Physiol. Heart Circ. Physiol. 286, H1603\u2013H1607 (2004).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"65349_CR9","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/s41569-020-0403-y","volume":"17","author":"G Heusch","year":"2020","unstructured":"Heusch, G. Myocardial ischaemia\u2013reperfusion injury and cardioprotection in perspective. Nat. Rev. Cardiol. 17, 773\u2013789 (2020).","journal-title":"Nat. Rev. Cardiol."},{"key":"65349_CR10","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1007\/s12265-018-9813-1","volume":"11","author":"JH Rosenberg","year":"2018","unstructured":"Rosenberg, J. H., Werner, J. H., Moulton, M. J. & Agrawal, D. K. Current modalities and mechanisms underlying cardioprotection by ischemic conditioning. J. Cardiovasc. Transl. Res. 11, 292\u2013307 (2018).","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"65349_CR11","doi-asserted-by":"publisher","first-page":"107424842311796","DOI":"10.1177\/10742484231179613","volume":"28","author":"G Heusch","year":"2023","unstructured":"Heusch, G. Cardioprotection and its translation: A need for new paradigms? Or for new pragmatism? An opinionated retro-and perspective. J. Cardiovasc. Pharmacol. Ther. 28, 10742484231179612 (2023).","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"65349_CR12","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1006\/jmcc.1997.0454","volume":"29","author":"JJ Schultz","year":"1997","unstructured":"Schultz, J. J., Hsu, A. K. & Gross, G. J. Ischemic preconditioning and morphine-induced cardioprotection involve the delta (\u03b4)-opioid receptor in the intact rat heart. J. Mol. Cell Cardiol. 29, 2187\u20132195 (1997).","journal-title":"J. Mol. Cell Cardiol."},{"key":"65349_CR13","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1161\/01.CIR.97.13.1282","volume":"97","author":"JEJ Schultz","year":"1998","unstructured":"Schultz, J. E. J., Hsu, A. K. & Gross, G. J. Ischemic preconditioning in the intact rat heart is mediated by \u03b41-but not \u03bc-or \u03ba-opioid receptors. Circulation 97, 1282\u20131289 (1998).","journal-title":"Circulation"},{"key":"65349_CR14","doi-asserted-by":"publisher","first-page":"H2157","DOI":"10.1152\/ajpheart.1995.268.5.H2157","volume":"268","author":"JEJ Schultz","year":"1995","unstructured":"Schultz, J. E. J., Rose, E., Yao, Z. & Gross, G. J. Evidence for involvement of opioid receptors in ischemic preconditioning in rat hearts. Am. J. Physiol. Heart Circ. Physiol. 268, H2157\u2013H2161 (1995).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"65349_CR15","doi-asserted-by":"publisher","first-page":"H384","DOI":"10.1152\/ajpheart.2001.280.1.H384","volume":"280","author":"G-Y Wang","year":"2001","unstructured":"Wang, G.-Y., Wu, S., Pei, J.-M., Yu, X.-C. & Wong, T.-M. \u03ba-But not \u03b4-opioid receptors mediate effects of ischemic preconditioning on both infarct and arrhythmia in rats. Am. J. Physiol. Heart Circ. Physiol. 280, H384\u2013H391 (2001).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"65349_CR16","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/S0008-6363(02)00316-4","volume":"55","author":"RM Fryer","year":"2002","unstructured":"Fryer, R. M., Auchampach, J. A. & Gross, G. J. Therapeutic receptor targets of ischemic preconditioning. Cardiovasc. Res. 55, 520\u2013525 (2002).","journal-title":"Cardiovasc. Res."},{"key":"65349_CR17","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1213\/ANE.0b013e3181b92201","volume":"109","author":"ER Gross","year":"2009","unstructured":"Gross, E. R., Hsu, A. K. & Gross, G. J. Acute methadone treatment reduces myocardial infarct size via the \u03b4-opioid receptor in rats during reperfusion. Anesth. Analg. 109, 1395\u20131402 (2009).","journal-title":"Anesth. Analg."},{"key":"65349_CR18","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1097\/ALN.0b013e318238bba6","volume":"115","author":"R Al-Hasani","year":"2011","unstructured":"Al-Hasani, R. & Bruchas, M. R. Molecular mechanisms of opioid receptor-dependent signaling and behavior. Anesthesiology 115, 1363\u20131381 (2011).","journal-title":"Anesthesiology"},{"key":"65349_CR19","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1007\/s12079-021-00653-z","volume":"16","author":"L Gopalakrishnan","year":"2022","unstructured":"Gopalakrishnan, L. et al. Opioid receptors signaling network. J. Cell Commun. Signal 16, 475\u2013483 (2022).","journal-title":"J. Cell Commun. Signal"},{"key":"65349_CR20","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1126\/scisignal.2000807","volume":"3","author":"A Gupta","year":"2010","unstructured":"Gupta, A. et al. Increased abundance of opioid receptor heteromers after chronic morphine administration. Sci. Signal. 3, 54 (2010).","journal-title":"Sci. Signal."},{"key":"65349_CR21","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.tips.2009.11.008","volume":"31","author":"R Rozenfeld","year":"2010","unstructured":"Rozenfeld, R. & Devi, L. A. Receptor heteromerization and drug discovery. Trends Pharmacol. Sci. 31, 124\u2013130 (2010).","journal-title":"Trends Pharmacol. Sci."},{"key":"65349_CR22","unstructured":"Yeganeh-Hajahmadi, M. Effect of Apelin on Cardiac Contractility in Acute Reno-Vascular Hypertension: The Role of Apelin Receptor and Kappa Opioid Receptor Heterodimerization. (2018). ncbi.nlm.nih.gov."},{"key":"65349_CR23","unstructured":"WHO. Opioid overdose. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/opioid-overdose."},{"key":"65349_CR24","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1016\/S0140-6736(19)32229-9","volume":"394","author":"L Degenhardt","year":"2019","unstructured":"Degenhardt, L. et al. Global patterns of opioid use and dependence: Harms to populations, interventions, and future action. Lancet 394, 1560\u20131579 (2019).","journal-title":"Lancet"},{"key":"65349_CR25","first-page":"6","volume":"67","author":"H Joseph","year":"2000","unstructured":"Joseph, H., Stancliff, S. & Langrod, J. Methadone maintenance treatment (MMT). Mount Sinai J. Med. 67, 6 (2000).","journal-title":"Mount Sinai J. Med."},{"key":"65349_CR26","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.jep.2009.11.011","volume":"127","author":"H Najafipour","year":"2010","unstructured":"Najafipour, H., Joukar, S., Malekpour-Afshar, R., Mirzaeipour, F. & Nasri, H. R. Passive opium smoking does not have beneficial effect on plasma lipids and cardiovascular indices in hypercholesterolemic rabbits with ischemic and non-ischemic hearts. J. Ethnopharmacol. 127, 257\u2013263 (2010).","journal-title":"J. Ethnopharmacol."},{"key":"65349_CR27","first-page":"182","volume":"1","author":"M Masoomi","year":"2010","unstructured":"Masoomi, M., Ramezani, M. A. & Karimzadeh, H. The relationship of opium addiction with coronary artery disease. Int. J. Prev. Med. 1, 182 (2010).","journal-title":"Int. J. Prev. Med."},{"key":"65349_CR28","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1097\/HJR.0b013e328045c4e9","volume":"14","author":"S Sadeghian","year":"2007","unstructured":"Sadeghian, S. et al. The association of opium with coronary artery disease. Eur. J. Cardiovasc. Prev. Rehabil. 14, 715\u2013717 (2007).","journal-title":"Eur. J. Cardiovasc. Prev. Rehabil."},{"key":"65349_CR29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/2008-7802.151431","volume":"6","author":"H Najafipour","year":"2015","unstructured":"Najafipour, H. et al. Effects of opium consumption on coronary artery disease risk factors and oral health: Results of Kerman coronary artery disease risk factors study a population-based survey on 5900 subjects aged 15\u201375 years. Int. J. Prev. Med. 6, 1\u201342 (2015).","journal-title":"Int. J. Prev. Med."},{"key":"65349_CR30","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/0091-3057(92)90451-K","volume":"42","author":"TL Pierce","year":"1992","unstructured":"Pierce, T. L., Tiong, G. K. L. & Olley, J. E. Morphine and methadone dependence in the rat: Withdrawal and brain met-enkephalin levels. Pharmacol. Biochem. Behav. 42, 91\u201396 (1992).","journal-title":"Pharmacol. Biochem. Behav."},{"key":"65349_CR31","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1159\/000338149","volume":"122","author":"X Duan","year":"2012","unstructured":"Duan, X. et al. Expression of microRNA-1 and microRNA-21 in different protocols of ischemic conditioning in an isolated rat heart model. Cardiology 122, 36\u201343 (2012).","journal-title":"Cardiology"},{"key":"65349_CR32","doi-asserted-by":"publisher","first-page":"1934","DOI":"10.1002\/jcb.25492","volume":"117","author":"V Siavashi","year":"2016","unstructured":"Siavashi, V., Nassiri, S. M., Rahbarghazi, R., Vafaei, R. & Sariri, R. ECM-dependence of endothelial progenitor cell features. J. Cell Biochem. 117, 1934\u20131946 (2016).","journal-title":"J. Cell Biochem."},{"key":"65349_CR33","doi-asserted-by":"publisher","first-page":"6090","DOI":"10.2174\/138161212803582360","volume":"18","author":"J Headrick","year":"2012","unstructured":"Headrick, J., Pepe, S. & Peart, J. Non-analgesic effects of opioids: Cardiovascular effects of opioids and their receptor systems. Curr. Pharm. Des. 18, 6090\u20136100 (2012).","journal-title":"Curr. Pharm. Des."},{"key":"65349_CR34","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1161\/CIRCRESAHA.116.305348","volume":"116","author":"G Heusch","year":"2015","unstructured":"Heusch, G. Molecular basis of cardioprotection: Signal transduction in ischemic pre-, post-, and remote conditioning. Circ. Res. 116, 674\u2013699 (2015).","journal-title":"Circ. Res."},{"key":"65349_CR35","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1161\/01.RES.74.5.998","volume":"74","author":"MV Cohen","year":"1994","unstructured":"Cohen, M. V., Yang, X.-M. & Downey, J. M. Conscious rabbits become tolerant to multiple episodes of ischemic preconditioning. Circ. Res. 74, 998\u20131004 (1994).","journal-title":"Circ. Res."},{"key":"65349_CR36","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1111\/j.1521-0391.2013.00308.x","volume":"22","author":"ECH Eyler","year":"2013","unstructured":"Eyler, E. C. H. Chronic and acute pain and pain management for patients in methadone maintenance treatment. Am. J. Addict. 22, 75\u201383 (2013).","journal-title":"Am. J. Addict."},{"key":"65349_CR37","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1016\/j.exger.2004.03.038","volume":"39","author":"JN Peart","year":"2004","unstructured":"Peart, J. N. & Gross, G. J. Chronic exposure to morphine produces a marked cardioprotective phenotype in aged mouse hearts. Exp. Gerontol. 39, 1021\u20131026 (2004).","journal-title":"Exp. Gerontol."},{"key":"65349_CR38","doi-asserted-by":"publisher","first-page":"T77","DOI":"10.1530\/JME-15-0323","volume":"56","author":"NX Cawley","year":"2016","unstructured":"Cawley, N. X., Li, Z. & Loh, Y. P. 60 YEARS OF POMC: Biosynthesis, trafficking, and secretion of pro-opiomelanocortin-derived peptides. J. Mol. Endocrinol. 56, T77\u2013T97 (2016).","journal-title":"J. Mol. Endocrinol."},{"key":"65349_CR39","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1146\/annurev-neuro-110719-095912","volume":"43","author":"MA Emery","year":"2020","unstructured":"Emery, M. A. & Akil, H. Endogenous opioids at the intersection of opioid addiction, pain, and depression: The search for a precision medicine approach. Annu. Rev. Neurosci. 43, 355\u2013374 (2020).","journal-title":"Annu. Rev. Neurosci."},{"key":"65349_CR40","doi-asserted-by":"publisher","first-page":"H1649","DOI":"10.1152\/ajpheart.00692.2008","volume":"295","author":"MD Goodman","year":"2008","unstructured":"Goodman, M. D., Koch, S. E., Fuller-Bicer, G. A. & Butler, K. L. Regulating RISK: A role for JAK-STAT signaling in postconditioning?. Am. J. Physiol. Heart Circ. Physiol. 295, H1649\u2013H1656 (2008).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"65349_CR41","doi-asserted-by":"publisher","first-page":"2128","DOI":"10.1172\/JCI23073","volume":"115","author":"T Nagoshi","year":"2005","unstructured":"Nagoshi, T. et al. PI3K rescues the detrimental effects of chronic Akt activation in the heart during ischemia\/reperfusion injury. J. Clin. Invest. 115, 2128\u20132138 (2005).","journal-title":"J. Clin. Invest."},{"key":"65349_CR42","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1002\/bies.200900005","volume":"31","author":"M Los","year":"2009","unstructured":"Los, M., Maddika, S., Erb, B. & Schulze-Osthoff, K. Switching Akt: From survival signaling to deadly response. Bioessays 31, 492\u2013495 (2009).","journal-title":"Bioessays"},{"key":"65349_CR43","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.brainresbull.2021.03.009","volume":"171","author":"E Nylander","year":"2021","unstructured":"Nylander, E., Zelleroth, S., Nyberg, F., Gr\u00f6nbladh, A. & Hallberg, M. The effects of morphine, methadone, and fentanyl on mitochondria: A live cell imaging study. Brain Res. Bull. 171, 126\u2013134 (2021).","journal-title":"Brain Res. Bull."},{"key":"65349_CR44","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1016\/j.bbadis.2010.07.024","volume":"1802","author":"S Perez-Alvarez","year":"2010","unstructured":"Perez-Alvarez, S. et al. Methadone induces necrotic-like cell death in SH-SY5Y cells by an impairment of mitochondrial ATP synthesis. Biochim. Biophys. Acta Mol. Basis Dis. 1802, 1036\u20131047 (2010).","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"65349_CR45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00395-021-00868-6","volume":"116","author":"HR Lieder","year":"2021","unstructured":"Lieder, H. R. et al. Cardioprotection by post-conditioning with exogenous triiodothyronine in isolated perfused rat hearts and isolated adult rat cardiomyocytes. Basic Res. Cardiol. 116, 1\u201315 (2021).","journal-title":"Basic Res. Cardiol."},{"key":"65349_CR46","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.005171","volume":"7","author":"X Yang","year":"2018","unstructured":"Yang, X. et al. Gastrin protects against myocardial ischemia\/reperfusion injury via activation of RISK (reperfusion injury salvage kinase) and SAFE (survivor activating factor enhancement) pathways. J. Am. Heart Assoc. 7, e005171 (2018).","journal-title":"J. Am. Heart Assoc."},{"key":"65349_CR47","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s00424-016-1922-6","volume":"469","author":"P Kleinbongard","year":"2017","unstructured":"Kleinbongard, P., Skyschally, A. & Heusch, G. Cardioprotection by remote ischemic conditioning and its signal transduction. Pfl\u00fcgers Arch. Eur. J. Physiol. 469, 159\u2013181 (2017).","journal-title":"Pfl\u00fcgers Arch. Eur. J. Physiol."},{"key":"65349_CR48","doi-asserted-by":"publisher","first-page":"5252","DOI":"10.1111\/bph.14839","volume":"177","author":"P Kleinbongard","year":"2020","unstructured":"Kleinbongard, P., B\u00f8tker, H. E., Ovize, M., Hausenloy, D. J. & Heusch, G. Co-morbidities and co-medications as confounders of cardioprotection: Does it matter in the clinical setting?. Br. J. Pharmacol. 177, 5252\u20135269 (2020).","journal-title":"Br. J. Pharmacol."},{"key":"65349_CR49","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1007\/s00395-022-00965-0","volume":"117","author":"P Kleinbongard","year":"2022","unstructured":"Kleinbongard, P. et al. Non-responsiveness to cardioprotection by ischaemic preconditioning in Ossabaw minipigs with genetic predisposition to, but without the phenotype of the metabolic syndrome. Basic Res. Cardiol. 117, 58 (2022).","journal-title":"Basic Res. Cardiol."},{"key":"65349_CR50","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1161\/CIRCRESAHA.117.310820","volume":"120","author":"G Heusch","year":"2017","unstructured":"Heusch, G. Critical issues for the translation of cardioprotection. Circ. Res. 120, 1477\u20131486 (2017).","journal-title":"Circ. Res."},{"key":"65349_CR51","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.medj.2023.12.007","volume":"5","author":"G Heusch","year":"2024","unstructured":"Heusch, G. Myocardial ischemia\/reperfusion: Translational pathophysiology of ischemic heart disease. Medicine 5, 10\u201331 (2024).","journal-title":"Medicine"},{"key":"65349_CR52","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.jacc.2018.09.086","volume":"73","author":"SM Davidson","year":"2019","unstructured":"Davidson, S. M. et al. Multitarget strategies to reduce myocardial ischemia\/reperfusion injury: JACC review topic of the week. J. Am. Coll. Cardiol. 73, 89\u201399 (2019).","journal-title":"J. Am. Coll. Cardiol."},{"key":"65349_CR53","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1007\/s00395-021-00893-5","volume":"116","author":"S Lecour","year":"2021","unstructured":"Lecour, S. et al. IMproving preclinical assessment of cardioprotective therapies (IMPACT) criteria: Guidelines of the EU-CARDIOPROTECTION COST action. Basic Res. Cardiol. 116, 52 (2021).","journal-title":"Basic Res. Cardiol."},{"key":"65349_CR54","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14146","volume":"7","author":"HR Lieder","year":"2019","unstructured":"Lieder, H. R., Irmert, A., Kamler, M., Heusch, G. & Kleinbongard, P. Sex is no determinant of cardioprotection by ischemic preconditioning in rats, but ischemic\/reperfused tissue mass is for remote ischemic preconditioning. Physiol. Rep. 7, e14146 (2019).","journal-title":"Physiol. Rep."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-65349-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-65349-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-65349-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T17:07:08Z","timestamp":1718989628000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-65349-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,21]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["65349"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-65349-x","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,21]]},"assertion":[{"value":"5 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 June 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 June 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14350"}}