{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:58:52Z","timestamp":1789167532196,"version":"build-2803163510"},"reference-count":56,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T00:00:00Z","timestamp":1629244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011660","name":"European Association of Cardiothoracic Anaesthesiology","doi-asserted-by":"publisher","award":["2018"],"award-info":[{"award-number":["2018"]}],"id":[{"id":"10.13039\/501100011660","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Remote ischemic preconditioning (RIPC) protects hearts from ischemia\u2013reperfusion (I\/R) injury in experimental studies; however, clinical RIPC trials were unsatisfactory. This discrepancy could be caused by a loss of cardioprotection due to comorbidities in patients, including diabetes mellitus (DM) and hyperglycemia (HG). RIPC is discussed to confer protective properties by release of different humoral factors activating cardioprotective signaling cascades. Therefore, we investigated whether DM type 1 and\/or HG (1) inhibit the release of humoral factors after RIPC and\/or (2) block the cardioprotective effect directly at the myocardium. Experiments were performed on male Wistar rats. Animals in part 1 of the study were either healthy normoglycemic (NG), type 1 diabetic (DM1), or hyperglycemic (HG). RIPC was implemented by four cycles of 5 min bilateral hind-limb ischemia\/reperfusion. Control (Con) animals were not treated. Blood plasma taken in vivo was further investigated in isolated rat hearts in vitro. Plasma from diseased animals (DM1 or HG) was administered onto healthy (NG) hearts for 10 min before 33 min of global ischemia and 60 min of reperfusion. Part 2 of the study was performed vice versa\u2014plasma taken in vivo, with or without RIPC, from healthy rats was transferred to DM1 and HG hearts in vitro. Infarct size was determined by TTC staining. Part 1: RIPC plasma from NG (NG Con: 49 \u00b1 8% vs. NG RIPC 29 \u00b1 6%; p &lt; 0.05) and DM1 animals (DM1 Con: 47 \u00b1 7% vs. DM1 RIPC: 38 \u00b1 7%; p &lt; 0.05) reduced infarct size. Interestingly, transfer of HG plasma showed comparable infarct sizes independent of prior treatment (HG Con: 34 \u00b1 9% vs. HG RIPC 35 \u00b1 9%; ns). Part 2: No infarct size reduction was detectable when transferring RIPC plasma from healthy rats to DM1 (DM1 Con: 54 \u00b1 13% vs. DM1 RIPC 53 \u00b1 10%; ns) or HG hearts (HG Con: 60 \u00b1 16% vs. HG RIPC 53 \u00b1 14%; ns). These results suggest that: (1) RIPC under NG and DM1 induces the release of humoral factors with cardioprotective impact, (2) HG plasma might own cardioprotective properties, and (3) RIPC does not confer cardioprotection in DM1 and HG myocardium.<\/jats:p>","DOI":"10.3390\/ijms22168880","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T10:54:35Z","timestamp":1629284075000},"page":"8880","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Influence of Hyperglycemia and Diabetes on Cardioprotection by Humoral Factors Released after Remote Ischemic Preconditioning (RIPC)"],"prefix":"10.3390","volume":"22","author":[{"given":"Carolin","family":"Torregroza","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Gnaegy","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, 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 Duesseldorf, Heinrich-Heine-University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Stroethoff","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Feige","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Heinen","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Physiology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus W.","family":"Hollmann","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Amsterdam University Medical Center (AUMC), Location AMC, Meiberdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ragnar","family":"Huhn","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e398","DOI":"10.3399\/bjgp19X702725","article-title":"Comorbidity in patients with cardiovascular disease in primary care: A cohort study with routine healthcare data","volume":"69","author":"Buddeke","year":"2019","journal-title":"Br. J. Gen. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition","volume":"157","author":"Saeedi","year":"2019","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1097\/00019501-199610000-00006","article-title":"Outcomes of diabetic patients following acute myocardial infarction: A review of the major thrombolytic trials","volume":"7","author":"Jelesoff","year":"1996","journal-title":"Coron. Artery Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/0002-9149(89)90836-9","article-title":"Hyperglycemia and prognosis of acute myocardial infarction in patients without diabetes mellitus","volume":"64","author":"Bellodi","year":"1989","journal-title":"Am. J. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.2337\/db14-0571","article-title":"Hyperglycemia and Adverse Outcomes in Acute Coronary Syndromes: Is Serum Glucose the Provocateur or Innocent Bystander?","volume":"63","author":"Wei","year":"2014","journal-title":"Diabetes"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1161\/CIRCULATIONAHA.110.985911","article-title":"Prognostic value of admission glycosylated hemoglobin and glucose in nondiabetic patients with ST-segment-elevation myocardial infarction treated with percutaneous coronary intervention","volume":"124","author":"Timmer","year":"2011","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1093\/eurheartj\/ehi049","article-title":"Acute hyperglycaemia: A \u2018new\u2019 risk factor during myocardial infarction","volume":"26","author":"Ceriello","year":"2004","journal-title":"Eur. Heart J."},{"key":"ref_8","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_9","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1056\/NEJMra071667","article-title":"Myocardial Reperfusion Injury","volume":"357","author":"Yellon","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_10","first-page":"27","article-title":"Remote Ischemic Conditioning: From Bench to Bedside","volume":"3","author":"Hausenloy","year":"2012","journal-title":"Front. Physiol."},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1161\/CIRCRESAHA.117.310820","article-title":"Critical Issues for the Translation of Cardioprotection","volume":"120","author":"Heusch","year":"2017","journal-title":"Circ. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1213\/ANE.0000000000005234","article-title":"Perioperative Cardioprotection: Clinical Implications","volume":"131","author":"Roth","year":"2020","journal-title":"Anesth. Analg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e008077","DOI":"10.1161\/JAHA.117.008077","article-title":"RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study: Myocardial Dysfunction, Postoperative Neurocognitive Dysfunction, and 1 Year Follow-Up","volume":"7","author":"Meybohm","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1056\/NEJMoa1413534","article-title":"Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery","volume":"373","author":"Hausenloy","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s12933-019-0872-7","article-title":"Impact of hyperglycemia on myocardial ischemia-reperfusion susceptibility and ischemic preconditioning in hearts from rats with type 2 diabetes","volume":"18","author":"Kristiansen","year":"2019","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/S0735-1097(01)01477-2","article-title":"Diabetes mellitus prevents ischemic preconditioning in patients with a first acute anterior wall myocardial infarction","volume":"38","author":"Ishihara","year":"2001","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5312","DOI":"10.1111\/bph.14993","article-title":"Effect of hyperglycaemia and diabetes on acute myocardial ischaemia-reperfusion injury and cardioprotection by ischaemic conditioning protocols","volume":"177","author":"Penna","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.2337\/diabetes.54.8.2360","article-title":"Preconditioning the Diabetic Heart. The Importance of Akt Phosphorylation","volume":"54","author":"Tsang","year":"2005","journal-title":"Diabetes"},{"key":"ref_20","first-page":"105","article-title":"Ameliorative potential of conditioning on ischemia-reperfusion injury in diabetes","volume":"1","author":"Rehni","year":"2018","journal-title":"Cond. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s11010-010-0500-z","article-title":"Involvement of GSK-3\u03b2 in attenuation of the cardioprotective effect of ischemic preconditioning in diabetic rat heart","volume":"343","author":"Yadav","year":"2010","journal-title":"Mol. Cell. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1161\/CIRCRESAHA.109.197996","article-title":"Role of glycogen synthase kinase-3beta in cardioprotection","volume":"104","author":"Juhaszova","year":"2009","journal-title":"Circ. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"329183","DOI":"10.1155\/2013\/329183","article-title":"Acute hyperglycemia abolishes ischemic preconditioning by inhibiting Akt phosphorylation: Normalizing blood glucose before ischemia restores ischemic preconditioning","volume":"2013","author":"Yang","year":"2013","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"H1744","DOI":"10.1152\/ajpheart.2001.280.4.H1744","article-title":"Diabetes and hyperglycemia impair activation of mitochondrial K(ATP) channels","volume":"280","author":"Kersten","year":"2001","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1186\/s12933-015-0313-1","article-title":"Acute hyperglycemia abolishes cardioprotection by remote ischemic perconditioning","volume":"14","author":"Baranyai","year":"2015","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_26","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_27","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1007\/s00395-016-0568-z","article-title":"Co-dependence of the neural and humoral pathways in the mechanism of remote ischemic conditioning","volume":"111","author":"Pickard","year":"2016","journal-title":"Basic Res. Cardiol."},{"key":"ref_28","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_29","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1097\/00000542-200303000-00029","article-title":"Modifying cardiovascular risk in diabetes mellitus","volume":"98","author":"Gu","year":"2003","journal-title":"Anesthesiology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1161\/01.CIR.0000027109.14149.67","article-title":"Impaired nitric oxide synthase pathway in diabetes mellitus: Role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase","volume":"106","author":"Lin","year":"2002","journal-title":"Circulation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.cardiores.2005.11.004","article-title":"Mitochondrial dysfunction as the cause of the failure to precondition the diabetic human myocardium","volume":"69","author":"Hassouna","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1177\/2047487318756420","article-title":"Signaling mediators modulated by cardioprotective interventions in healthy and diabetic myocardium with ischaemia-reperfusion injury","volume":"25","author":"Saeid","year":"2018","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1161\/CIRCRESAHA.116.305348","article-title":"Molecular basis of cardioprotection: Signal transduction in ischemic pre-, post-, and remote conditioning","volume":"116","author":"Heusch","year":"2015","journal-title":"Circ. Res."},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1172\/JCI109002","article-title":"Immediate and time-dependent effects of glucose on insulin release from rat pancreatic tissue. Evidence for different mechanisms of action","volume":"61","author":"Grill","year":"1978","journal-title":"J. Clin. Investig."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.2337\/diabetes.51.2007.S53","article-title":"Modeling phasic insulin release: Immediate and time-dependent effects of glucose","volume":"51","author":"Nesher","year":"2002","journal-title":"Diabetes"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1161\/CIRCULATIONAHA.111.063784","article-title":"Cardioprotective Effects of Insulin","volume":"125","author":"Ng","year":"2012","journal-title":"Circulation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.ejcts.2010.10.007","article-title":"Glucose\u2013insulin\u2013potassium therapy in adult patients undergoing cardiac surgery: A meta-analysis","volume":"40","author":"Fan","year":"2011","journal-title":"Eur. J. Cardio Thorac. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1210\/jc.2011-2037","article-title":"Tight Glycemic Control May Increase Regenerative Potential of Myocardium during Acute Infarction","volume":"97","author":"Marfella","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3106056","DOI":"10.1155\/2018\/3106056","article-title":"Role of Tight Glycemic Control during Acute Coronary Syndrome on CV Outcome in Type 2 Diabetes","volume":"2018","author":"Sasso","year":"2018","journal-title":"J. Diabetes Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/BF02913315","article-title":"Induction of diabetes by Streptozotocin in rats","volume":"22","author":"Akbarzadeh","year":"2007","journal-title":"Indian J. Clin. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1161\/CIRCRESAHA.111.253104","article-title":"Dietary fat and heart failure: Moving from lipotoxicity to lipoprotection","volume":"110","author":"Stanley","year":"2012","journal-title":"Circ. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.4239\/wjd.v6.i13.1246","article-title":"Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research","volume":"6","author":"Leon","year":"2015","journal-title":"World J. Diabetes"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s12933-021-01343-1","article-title":"Efficacy and durability of multifactorial intervention on mortality and MACEs: A randomized clinical trial in type-2 diabetic kidney disease","volume":"20","author":"Sasso","year":"2021","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Roth, S., Torregroza, C., Feige, K., Preckel, B., Hollmann, M.W., Weber, N.C., and Huhn, R. (2021). Pharmacological Conditioning of the Heart: An Update on Experimental Developments and Clinical Implications. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052519"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jacc.2018.09.086","article-title":"Multitarget Strategies to Reduce Myocardial Ischemia\/Reperfusion Injury: JACC Review Topic of the Week","volume":"73","author":"Davidson","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41569-020-0403-y","article-title":"Myocardial ischaemia-reperfusion injury and cardioprotection in perspective","volume":"17","author":"Heusch","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_48","unstructured":"National Research Council Committee for the Update of the Guide for the Care and Use of Laboratory Animals (2010). Guide for the Care and Use of Laboratory Animals, National Academies Press (US). [8th ed.]."},{"key":"ref_49","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_50","doi-asserted-by":"crossref","first-page":"3115","DOI":"10.1161\/CIRCULATIONAHA.105.563817","article-title":"Cardioprotection by intermittent fasting in rats","volume":"112","author":"Ahmet","year":"2005","journal-title":"Circulation"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"567","DOI":"10.33549\/physiolres.932338","article-title":"Short-term fasting reduces the extent of myocardial infarction and incidence of reperfusion arrhythmias in rats","volume":"61","author":"Snorek","year":"2012","journal-title":"Physiol. Res."},{"key":"ref_52","first-page":"9051426","article-title":"Experimental Diabetes Mellitus in Different Animal Models","volume":"2016","author":"Kupai","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_53","first-page":"181","article-title":"Streptozotocin-induced type 1 diabetes in rodents as a model for studying mitochondrial mechanisms of diabetic \u03b2 cell glucotoxicity","volume":"8","author":"Wu","year":"2015","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/0471141755.ph0547s70","article-title":"Streptozotocin-Induced Diabetic Models in Mice and Rats","volume":"70","author":"Furman","year":"2015","journal-title":"Curr. Protoc. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Raupach, A., Reinle, J., Stroethoff, M., Mathes, A., Heinen, A., Hollmann, M.W., Huhn, R., and Bunte, S. (2019). Milrinone-Induced Pharmacological Preconditioning in Cardioprotection: Hints for a Role of Mitochondrial Mechanisms. J. Clin. Med., 8.","DOI":"10.3390\/jcm8040507"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Behmenburg, F., Dorsch, M., Huhn, R., Mally, D., Heinen, A., Hollmann, M.W., and Berger, M.M. (2015). Impact of Mitochondrial Ca2+-Sensitive Potassium (mBKCa) Channels in Sildenafil-Induced Cardioprotection in Rats. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144737"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8880\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:46:26Z","timestamp":1760165186000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8880"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,18]]},"references-count":56,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22168880"],"URL":"https:\/\/doi.org\/10.3390\/ijms22168880","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,18]]}}}