{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:37:49Z","timestamp":1791319069274,"version":"4.3.1"},"reference-count":32,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,12]],"date-time":"2024-10-12T00:00:00Z","timestamp":1728691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endothelial dysfunction (ED) is closely associated with most cardiovascular diseases. Experimental models are needed to analyze the potential impact of ED on cardioprotection in constant pressure Langendorff systems (CPLS). One cardioprotective strategy against ischemia\/reperfusion injury (I\/RI) is conditioning with the lipid emulsion Intralipid (IL). Whether ED modulates the cardioprotective effect of IL remains unknown. The aim of the study was to transfer a protocol using a constant flow Langendorff system for the induction of ED into a CPLS, without the loss of smooth muscle cell functionality, and to analyze the cardioprotective effect of IL against I\/RI under ED. In isolated hearts of male Wistar rats, ED was induced by 10 min perfusion of a Krebs\u2013Henseleit buffer containing 60 mM KCl (K+), and the vasodilatory response to the vasodilators histamine (endothelial-dependent) and sodium\u2013nitroprusside (SNP, endothelial-independent) was measured. A CPLS was employed to determine cardioprotection of pre- or postconditioning with 1% IL against I\/RI. The constant flow perfusion of K+ reduced endothelial response to histamine but not to SNP, indicating reduced vasodilatory functionality of endothelial cells but not smooth muscle cells. Preconditioning with IL reduced infarct size and improved cardiac function while postconditioning with IL had no effect. The induction of ED neither influenced infarct size nor affected the cardioprotective effect by preconditioning with IL. This protocol allows for studies of cardioprotective strategies under ED in CLPS. The protection by preconditioning with IL seems to be mediated independently of a functional endothelium.<\/jats:p>","DOI":"10.3390\/ijms252010975","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T04:02:58Z","timestamp":1728878578000},"page":"10975","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cardioprotection by Preconditioning with Intralipid Is Sustained in a Model of Endothelial Dysfunction for Isolated-Perfused Hearts"],"prefix":"10.3390","volume":"25","author":[{"given":"Martin","family":"Stroethoff","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich-Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich-Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich-Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"W\u00fcbbolt","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich-Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Heinen","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Physiology, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich-Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5257-1022","authenticated-orcid":false,"given":"Annika","family":"Raupach","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich-Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e139","DOI":"10.1161\/CIR.0000000000000757","article-title":"Heart Disease and Stroke Statistics-2020 Update: A Report from the American Heart Association","volume":"141","author":"Virani","year":"2020","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global Burden of Cardiovascular Diseases and Risk Factors, 1990\u20132019: Update from the GBD 2019 Study","volume":"76","author":"Roth","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1213\/ANE.0000000000005243","article-title":"Perioperative Cardioprotection: General Mechanisms and Pharmacological Approaches","volume":"131","author":"Torregroza","year":"2020","journal-title":"Anesth. Analg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1097\/ALN.0b013e318223b8b9","article-title":"Phosphorylation of GSK-3beta mediates intralipid-induced cardioprotection against ischemia\/reperfusion injury","volume":"115","author":"Rahman","year":"2011","journal-title":"Anesthesiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1097\/ALN.0b013e3182655e73","article-title":"Intralipid, a clinically safe compound, protects the heart against ischemia-reperfusion injury more efficiently than cyclosporine-A","volume":"117","author":"Li","year":"2012","journal-title":"Anesthesiology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1007\/s12630-019-01322-x","article-title":"Enhanced myocardial protection in cardiac donation after circulatory death using Intralipid((R)) postconditioning in a porcine model","volume":"66","author":"Lucchinetti","year":"2019","journal-title":"Can. J. Anaesth."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.trsl.2017.05.007","article-title":"Postconditioning with Intralipid emulsion protects against reperfusion injury in post-infarct remodeled rat hearts by activation of ROS-Akt\/Erk signaling","volume":"186","author":"Zaugg","year":"2017","journal-title":"Transl. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10742484231179613","DOI":"10.1177\/10742484231179613","article-title":"Cardioprotection and its Translation: A Need for New Paradigms? Or for New Pragmatism? An Opinionated Retro- and Perspective","volume":"28","author":"Heusch","year":"2023","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"H398","DOI":"10.1152\/ajpheart.00256.2023","article-title":"Endothelial dysfunction at the cellular level in three dimensions: Severity, acuteness, and distribution","volume":"325","author":"Segers","year":"2023","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Roy, R., Wilcox, J., Webb, A.J., and O\u2019Gallagher, K. (2023). Dysfunctional and Dysregulated Nitric Oxide Synthases in Cardiovascular Disease: Mechanisms and Therapeutic Potential. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242015200"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.ccc.2019.12.009","article-title":"Nitric Oxide and Endothelial Dysfunction","volume":"36","author":"Cyr","year":"2020","journal-title":"Crit. Care Clin."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1161\/01.RES.72.4.768","article-title":"Effect of dysfunctional vascular endothelium on myocardial performance in isolated papillary muscles","volume":"72","author":"Li","year":"1993","journal-title":"Circ. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1093\/oxfordjournals.eurheartj.a060303","article-title":"Ischaemic endothelial dysfunction after single or multidose cardioplegia","volume":"13","author":"Mankad","year":"1992","journal-title":"Eur. Heart J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s003950050091","article-title":"Coronary endothelial dysfunction increases the severity of ischaemia-induced ventricular arrhythmias in rat isolated perfused hearts","volume":"93","author":"Hassanabad","year":"1998","journal-title":"Basic. Res. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"He, L., Hao, S., Wang, Y., Yang, W., Liu, L., Chen, H., and Qian, J. (2019). Dexmedetomidine preconditioning attenuates ischemia\/reperfusion injury in isolated rat hearts with endothelial dysfunction. Biomed. Pharmacother., 114.","DOI":"10.1016\/j.biopha.2019.108837"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/0003-4975(93)90278-P","article-title":"Effects of pressure and duration of hyperkalemic infusions on endothelial function","volume":"55","author":"Cartier","year":"1993","journal-title":"Ann. Thorac. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.vascn.2006.05.006","article-title":"Isolated heart perfusion according to Langendorff---still viable in the new millennium","volume":"55","author":"Grotthus","year":"2007","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"H812","DOI":"10.1152\/ajpheart.00335.2017","article-title":"Guidelines for experimental models of myocardial ischemia and infarction","volume":"314","author":"Lindsey","year":"2018","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Neumann, J., Hofmann, B., Kirchhefer, U., Dhein, S., and Gergs, U. (2023). Function and Role of Histamine H(1) Receptor in the Mammalian Heart. Pharmaceuticals, 16.","DOI":"10.3390\/ph16050734"},{"key":"ref_20","unstructured":"Holme, M.R., and Sharman, T. (2024). Sodium Nitroprusside, StatPearls."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1213\/ANE.0000000000005148","article-title":"Dexmedetomidine Provides Cardioprotection during Early or Late Reperfusion Mediated by Different Mitochondrial K+-Channels","volume":"132","author":"Raupach","year":"2021","journal-title":"Anesth. Analg."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Torregroza, C., Feige, K., Schneider, L., Bunte, S., Stroethoff, M., Heinen, A., Hollmann, M.W., Huhn, R., and Raupach, A. (2020). Influence of Hyperglycemia on Dexmedetomidine-Induced Cardioprotection in the Isolated Perfused Rat Heart. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051445"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.annemergmed.2015.01.020","article-title":"Confusion About Infusion: Rational Volume Limits for Intravenous Lipid Emulsion during Treatment of Oral Overdoses","volume":"66","author":"Fettiplace","year":"2015","journal-title":"Ann. Emerg. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1097\/SHK.0000000000000130","article-title":"Ventricular hypertrophy abrogates intralipid-induced cardioprotection by alteration of reperfusion injury salvage kinase\/glycogen synthase kinase 3beta signal","volume":"41","author":"Ma","year":"2014","journal-title":"Shock."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.phrs.2015.11.004","article-title":"Dexmedetomidine protects the heart against ischemia-reperfusion injury by an endothelial eNOS\/NO dependent mechanism","volume":"103","author":"Riquelme","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"170333","DOI":"10.1016\/j.peptides.2020.170333","article-title":"Oxytocin mediated cardioprotection is independent of coronary endothelial function in rats","volume":"130","author":"Wang","year":"2020","journal-title":"Peptides"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.lfs.2012.03.030","article-title":"Is preconditioning by oxytocin administration mediated by iNOS and\/or mitochondrial K(ATP) channel activation in the in vivo anesthetized rabbit heart?","volume":"90","author":"Das","year":"2012","journal-title":"Life Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1002\/jpen.1834","article-title":"Intralipid Increases Nitric Oxide Release from Human Endothelial Cells during Oxidative Stress","volume":"45","author":"Weihrauch","year":"2021","journal-title":"JPEN J. Parenter. Enter. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11113","DOI":"10.1007\/s11033-022-07889-x","article-title":"Quantitative aspects of nitric oxide production in the heart","volume":"49","author":"Ghasemi","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/S0008-6363(99)00343-0","article-title":"Participation of prostaglandin E2 in the endothelial protective effect of ischaemic preconditioning in isolated rat heart","volume":"45","author":"Bouchard","year":"2000","journal-title":"Cardiovasc. Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lou, P.H., Lucchinetti, E., Zhang, L., Affolter, A., Schaub, M.C., Gandhi, M., Hersberger, M., Warren, B.E., Lemieux, H., and Sobhi, H.F. (2014). The mechanism of Intralipid(R)-mediated cardioprotection complex IV inhibition by the active metabolite, palmitoylcarnitine, generates reactive oxygen species and activates reperfusion injury salvage kinases. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087205"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3758\/BF03193146","article-title":"G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences","volume":"39","author":"Faul","year":"2007","journal-title":"Behav. Res. 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