{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T02:52:10Z","timestamp":1788576730213,"version":"build-2803163510"},"reference-count":46,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Funding of the Faculty of Medicine, Ruhr University Bochum","award":["F945N-19"],"award-info":[{"award-number":["F945N-19"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Remote ischemic preconditioning (RIPC) reduces ischemia-reperfusion injury in aortocoronary bypass surgery, potentially via extracellular vesicles (EVs) and their micro-RNA content. Clinical data implicate that propofol might inhibit the cardioprotective RIPC effect. This prospective, randomized study investigated the influence of different anesthetic regimes on RIPC efficacy and EV micro-RNA signatures. We also assessed the impact of propofol on cell protection after hypoxic conditioning and EV-mediated RIPC in vitro. H9c2 rat cardiomyoblasts were subjected to hypoxia, with or without propofol, and subsequent simulated ischemia-reperfusion injury. Apoptosis was measured by flow cytometry. Blood samples of 64 patients receiving anesthetic maintenance with propofol or isoflurane, along with RIPC or sham procedures, were analyzed, and EVs were enriched using a polymer-based method. Propofol administration corresponded with increased Troponin T levels (4669 \u00b1 435.6 pg\/mL), suggesting an inhibition of the cardioprotective RIPC effect. RIPC leads to a notable rise in miR-21 concentrations in the group receiving propofol anesthesia (fold change 7.22 \u00b1 6.6). In vitro experiments showed that apoptosis reduction was compromised with propofol and only occurred in an EV-enriched preconditioning medium, not in an EV-depleted medium. Our study could clinically and experimentally confirm propofol inhibition of RIPC protection. Increased miR-21 expression could provide evidence for a possible inhibitory mechanism.<\/jats:p>","DOI":"10.3390\/ijms25179304","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T03:57:06Z","timestamp":1724817426000},"page":"9304","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Influence of Anesthetic Regimes on Extracellular Vesicles following Remote Ischemic Preconditioning in Coronary Artery Disease"],"prefix":"10.3390","volume":"25","author":[{"given":"Phuong N. V.","family":"Pham","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, Pain and Palliative Care, Marien Hospital Herne, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loubna","family":"Yahsaly","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5744-8661","authenticated-orcid":false,"given":"Crista","family":"Ochsenfarth","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, Pain and Palliative Care, Marien Hospital Herne, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2446-948X","authenticated-orcid":false,"given":"Bernd","family":"Giebel","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romina","family":"Schnitzler","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care and Pain Medicine, BG University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Zahn","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care and Pain Medicine, BG University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich H.","family":"Frey","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, Pain and Palliative Care, Marien Hospital Herne, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"216","DOI":"10.18632\/oncotarget.26537","article-title":"Circulating Mediators of Remote Ischemic Preconditioning: Search for the Missing Link between Non-Lethal Ischemia and Cardioprotection","volume":"10","author":"Billah","year":"2019","journal-title":"Oncotarget"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"ehw224","DOI":"10.1093\/eurheartj\/ehw224","article-title":"The Pathophysiology of Acute Myocardial Infarction and Strategies of Protection beyond Reperfusion: A Continual Challenge","volume":"38","author":"Heusch","year":"2016","journal-title":"Eur. Hear. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/S0140-6736(07)61296-3","article-title":"Effect of Remote Ischaemic Preconditioning on Myocardial Injury in Patients Undergoing Coronary Artery Bypass Graft Surgery: A Randomised Controlled Trial","volume":"370","author":"Hausenloy","year":"2007","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1161\/01.CIR.96.5.1641","article-title":"Ischemic Preconditioning at a Distance: Reduction of Myocardial Infarct Size by Partial Reduction of Blood Supply Combined With Rapid Stimulation of the Gastrocnemius Muscle in the Rabbit","volume":"96","author":"Birnbaum","year":"1997","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1056\/NEJMoa1413579","article-title":"A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery","volume":"373","author":"Meybohm","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/eme03040","article-title":"Effect of Remote Ischaemic Preconditioning on Clinical Outcomes in Patients Undergoing Coronary Artery Bypass Graft Surgery (ERICCA Study): A Multicentre Double-Blind Randomised Controlled Clinical Trial","volume":"3","author":"Hausenloy","year":"2016","journal-title":"Effic. Mech. Eval."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/j.1399-6576.2011.02585.x","article-title":"Anesthesia and Remote Ischemic Preconditioning","volume":"56","author":"Kottenberg","year":"2012","journal-title":"Acta Anaesth. Scand."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1213\/ANE.0000000000002563","article-title":"Impact of Anesthetic Regimen on Remote Ischemic Preconditioning in the Rat Heart In Vivo","volume":"126","author":"Behmenburg","year":"2018","journal-title":"Anesth. Analg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e250","DOI":"10.1097\/CCM.0000000000003629","article-title":"Cardioprotection by Humoral Factors Released After Remote Ischemic Preconditioning Depends on Anesthetic Regimen","volume":"47","author":"Bunte","year":"2019","journal-title":"Crit. Care Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4535","DOI":"10.1002\/jcb.29671","article-title":"The Timing of Propofol Administration Affects the Effectiveness of Remote Ischemic Preconditioning Induced Cardioprotection in Rats","volume":"121","author":"Chen","year":"2020","journal-title":"J. Cell Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3857","DOI":"10.1007\/s11010-021-04192-4","article-title":"Myocardial Remote Ischemic Preconditioning: From Cell Biology to Clinical Application","volume":"476","author":"Donato","year":"2021","journal-title":"Mol. Cell Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1161\/CIRCRESAHA.116.305348","article-title":"Molecular Basis of Cardioprotection","volume":"116","author":"Heusch","year":"2015","journal-title":"Circ. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.metabol.2018.04.008","article-title":"Extracellular Vesicles Characteristics and Emerging Roles in Atherosclerotic Cardiovascular Disease","volume":"85","author":"Hafiane","year":"2018","journal-title":"Metabolis"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e12151","DOI":"10.1002\/jev2.12151","article-title":"In Sickness and in Health: The Functional Role of Extracellular Vesicles in Physiology and Pathology in Vivo","volume":"11","author":"Yates","year":"2022","journal-title":"J. Extracell. Vesicles"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4989","DOI":"10.1113\/JP283200","article-title":"Extracellular Vesicles and Their Non-coding RNA Cargos: Emerging Players in Cardiovascular Disease","volume":"601","author":"Collado","year":"2022","journal-title":"J. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.yjmcc.2014.01.004","article-title":"Cardioprotection by Remote Ischemic Preconditioning of the Rat Heart Is Mediated by Extracellular Vesicles","volume":"68","author":"Giricz","year":"2014","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1161\/CIRCRESAHA.113.300636","article-title":"Exosomes","volume":"114","author":"Yellon","year":"2014","journal-title":"Circ. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1016\/j.jacc.2015.02.026","article-title":"Plasma Exosomes Protect the Myocardium From Ischemia-Reperfusion Injury","volume":"65","author":"Vicencio","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s00395-021-00856-w","article-title":"Cardioprotection by Remote Ischemic Conditioning Is Transferable by Plasma and Mediated by Extracellular Vesicles","volume":"116","author":"Lassen","year":"2021","journal-title":"Basic Res. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Brennan, K., Martin, K., FitzGerald, S.P., O\u2019Sullivan, J., Wu, Y., Blanco, A., Richardson, C., and Gee, M.M.M. (2020). A Comparison of Methods for the Isolation and Separation of Extracellular Vesicles from Protein and Lipid Particles in Human Serum. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-57497-7"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"S\u00f3dar, B.W., Kittel, \u00c1., P\u00e1l\u00f3czi, K., Vukman, K.V., Osteikoetxea, X., Szab\u00f3-Taylor, K., N\u00e9meth, A., Sperl\u00e1gh, B., Baranyai, T., and Giricz, Z. (2016). Low-Density Lipoprotein Mimics Blood Plasma-Derived Exosomes and Microvesicles during Isolation and Detection. Sci. Rep., 6.","DOI":"10.1038\/srep24316"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1161\/CIRCULATIONAHA.120.049254","article-title":"Therapeutic and Diagnostic Translation of Extracellular Vesicles in Cardiovascular Diseases","volume":"143","author":"Sahoo","year":"2021","journal-title":"Circulation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/aas.13296","article-title":"Remote Ischaemic Preconditioning Increases Serum Extracellular Vesicle Concentrations with Altered Micro-RNA Signature in CABG Patients","volume":"63","author":"Frey","year":"2019","journal-title":"Acta Anaesth. Scand."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1097\/SHK.0000000000001156","article-title":"MiRNA-Mediated Mechanisms of Cardiac Protection in Ischemic and Remote Ischemic Preconditioning\u2014A Qualitative Systematic Review","volume":"51","author":"Kohns","year":"2019","journal-title":"Shock"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/cvr\/cvq082","article-title":"Ischaemic Preconditioning-Regulated MiR-21 Protects Heart against Ischaemia\/Reperfusion Injury via Anti-Apoptosis through Its Target PDCD4","volume":"87","author":"Cheng","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.ijcard.2016.11.198","article-title":"Remote Ischemic Preconditioning Attenuates EGR-1 Expression Following Myocardial Ischemia Reperfusion Injury through Activation of the JAK-STAT Pathway","volume":"228","author":"Mudaliar","year":"2017","journal-title":"Int. J. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1002\/jcb.26501","article-title":"Acute Hypoxic Preconditioning Prevents Palmitic Acid-induced Cardiomyocyte Apoptosis via Switching Metabolic GLUT4-glucose Pathway Back to CD36-fatty Acid Dependent","volume":"119","author":"Chen","year":"2018","journal-title":"J. Cell. Biochem."},{"key":"ref_28","first-page":"7378","article-title":"Hypoxic Preconditioning Protects Cardiomyocytes against Hypoxia\/Reoxygenation Injury through AMPK\/ENOS\/PGC-1\u03b1 Signaling Pathway","volume":"7","author":"Hu","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Yan, Y., Gu, T., Christensen, S.D.K., Su, J., Lassen, T.R., Hjortbak, M.V., Lo, I.J., Ven\u00f8, S.T., T\u00f3th, A.E., and Song, P. (2021). Cyclic Hypoxia Conditioning Alters the Content of Myoblast-Derived Extracellular Vesicles and Enhances Their Cell-Protective Functions. Biomedicines, 9.","DOI":"10.3390\/biomedicines9091211"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Abel, F., Murke, F., Gaida, M., Garnier, N., Ochsenfarth, C., Theiss, C., Thielmann, M., Kleinbongard, P., Giebel, B., and Peters, J. (2020). Extracellular Vesicles Isolated from Patients Undergoing Remote Ischemic Preconditioning Decrease Hypoxia-Evoked Apoptosis of Cardiomyoblasts after Isoflurane but Not Propofol Exposure. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0228948"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s00395-014-0423-z","article-title":"MicroRNA-144 Is a Circulating Effector of Remote Ischemic Preconditioning","volume":"109","author":"Li","year":"2014","journal-title":"Basic Res. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.jtcvs.2013.01.005","article-title":"Interference of Propofol with Signal Transducer and Activator of Transcription 5 Activation and Cardioprotection by Remote Ischemic Preconditioning during Coronary Artery Bypass Grafting","volume":"147","author":"Kottenberg","year":"2014","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zangrillo, A., Musu, M., Greco, T., Prima, A.L.D., Matteazzi, A., Testa, V., Nardelli, P., Febres, D., Monaco, F., and Calabr\u00f2, M.G. (2015). Additive Effect on Survival of Anaesthetic Cardiac Protection and Remote Ischemic Preconditioning in Cardiac Surgery: A Bayesian Network Meta-Analysis of Randomized Trials. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134264"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1097\/00000542-200403000-00035","article-title":"Mechanisms of Cardioprotection by Volatile Anesthetics","volume":"100","author":"Tanaka","year":"2004","journal-title":"J. Am. Soc. Anesthesiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3542149","DOI":"10.1155\/2017\/3542149","article-title":"Inhibition of Caveolae Contributes to Propofol Preconditioning-Suppressed Microvesicles Release and Cell Injury by Hypoxia-Reoxygenation","volume":"2017","author":"Deng","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Torregroza, C., Gnaegy, L., Raupach, A., Stroethoff, M., Feige, K., Heinen, A., Hollmann, M.W., and Huhn, R. (2021). Influence of Hyperglycemia and Diabetes on Cardioprotection by Humoral Factors Released after Remote Ischemic Preconditioning (RIPC). Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168880"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s00395-012-0285-1","article-title":"Release of a Humoral Circulating Cardioprotective Factor by Remote Ischemic Preconditioning Is Dependent on Preserved Neural Pathways in Diabetic Patients","volume":"107","author":"Jensen","year":"2012","journal-title":"Basic Res. Cardiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"29514","DOI":"10.1074\/jbc.M109.027896","article-title":"MicroRNA Expression Signature and the Role of MicroRNA-21 in the Early Phase of Acute Myocardial Infarction","volume":"284","author":"Dong","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Tu, Y., Wan, L., Fan, Y., Wang, K., Bu, L., Huang, T., Cheng, Z., and Shen, B. (2013). Ischemic Postconditioning-Mediated MiRNA-21 Protects against Cardiac Ischemia\/Reperfusion Injury via PTEN\/Akt Pathway. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075872"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1161\/CIRCRESAHA.108.193250","article-title":"A Novel Role of MicroRNA in Late Preconditioning","volume":"104","author":"Yin","year":"2009","journal-title":"Circ. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1161\/ATVBAHA.111.241471","article-title":"Intracellular Trafficking and Secretion of VLDL","volume":"32","author":"Tiwari","year":"2012","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1528109","DOI":"10.1080\/20013078.2018.1528109","article-title":"Precipitation with Polyethylene Glycol Followed by Washing and Pelleting by Ultracentrifugation Enriches Extracellular Vesicles from Tissue Culture Supernatants in Small and Large Scales","volume":"7","author":"Ludwig","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Doyle, L.M., and Wang, M.Z. (2019). Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells, 8.","DOI":"10.3390\/cells8070727"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"19861","DOI":"10.3402\/jev.v2i0.19861","article-title":"How Pure Are Your Vesicles?","volume":"2","author":"Webber","year":"2013","journal-title":"J. Extracell. Vesicles"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Engler, A., Dreja, F., K\u00f6berle, S., Thielmann, M., Peters, J., and Frey, U.H. (2018). Establishment of an Easy and Straight Forward Heparinase Protocol to Analyse Circulating and Myocardial Tissue Micro-RNA during Coronary Artery-Bypass-Graft Surgery. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-19748-6"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9304\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:43:55Z","timestamp":1760111035000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,28]]},"references-count":46,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms25179304"],"URL":"https:\/\/doi.org\/10.3390\/ijms25179304","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,28]]}}}