{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T22:34:06Z","timestamp":1783463646899,"version":"3.55.0"},"reference-count":63,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2017,9,9]],"date-time":"2017-09-09T00:00:00Z","timestamp":1504915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004061","name":"Oesterreichische Nationalbank","doi-asserted-by":"publisher","award":["16435"],"award-info":[{"award-number":["16435"]}],"id":[{"id":"10.13039\/501100004061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P24946"],"award-info":[{"award-number":["P24946"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The antioxidant 5\u2010hydroxymethylfurfural (5\u2010HMF) exerts documented beneficial effects in several experimental pathologies and is currently tested as an antisickling drug in clinical trials. In the present study, we examined the cardiovascular effects of 5\u2010HMF and elucidated the mode of action of the drug.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The cardiovascular effects of 5\u2010HMF were studied with pre\u2010contracted porcine coronary arteries and rat isolated normoxic\u2010perfused hearts. Isolated hearts subjected to ischaemia\/reperfusion (I\/R) injury were used to test for potential cardioprotective effects of the drug. The effects of 5\u2010HMF on action potential and L\u2010type Ca<jats:sup>2+<\/jats:sup> current (I<jats:sub>Ca,L<\/jats:sub>) were studied by patch\u2010clamping guinea pig isolated ventricular cardiomyocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>5\u2010HMF relaxed coronary arteries in a concentration\u2010dependent manner and exerted negative inotropic, lusitropic and chronotropic effects in rat isolated perfused hearts. On the other hand, 5\u2010HMF improved recovery of inotropic and lusitropic parameters in isolated hearts subjected to I\/R. Patch clamp experiments revealed that 5\u2010HMF inhibits L\u2010type Ca<jats:sup>2+<\/jats:sup> channels. Reduced I<jats:sub>Ca,L<\/jats:sub> density, shift of I<jats:sub>Ca,L<\/jats:sub> steady\u2010state inactivation curves toward negative membrane potentials and slower recovery of I<jats:sub>Ca,L<\/jats:sub> from inactivation in response to 5\u2010HMF accounted for the observed cardiovascular effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Our data revealed a cardioprotective effect of 5\u2010HMF in I\/R that is mediated by inhibition of L\u2010type Ca<jats:sup>2+<\/jats:sup> channels. Thus, 5\u2010HMF is suggested as a beneficial additive to cardioplegic solutions, but adverse effects and contraindications of Ca<jats:sup>2+<\/jats:sup> channel blockers have to be considered in therapeutic application of the drug.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13967","type":"journal-article","created":{"date-parts":[[2017,8,2]],"date-time":"2017-08-02T16:26:38Z","timestamp":1501691198000},"page":"3640-3653","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Cardioprotective effects of 5\u2010hydroxymethylfurfural mediated by inhibition of L\u2010type Ca<sup>2+<\/sup> currents"],"prefix":"10.1111","volume":"174","author":[{"given":"G","family":"W\u00f6lkart","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Department of Pharmacology and Toxicology University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Schrammel","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Department of Pharmacology and Toxicology University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C N","family":"Koyani","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biochemistry Medical University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Scher\u00fcbel","sequence":"additional","affiliation":[{"name":"Institute of Biophysics Medical University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Zorn\u2010Pauly","sequence":"additional","affiliation":[{"name":"Institute of Biophysics Medical University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Malle","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biochemistry Medical University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Pelzmann","sequence":"additional","affiliation":[{"name":"Institute of Biophysics Medical University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Andr\u00e4","sequence":"additional","affiliation":[{"name":"Department of Thoracic and Cardiovascular Surgery Klinikum Klagenfurt  Klagenfurt Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8604-1273","authenticated-orcid":false,"given":"A","family":"Ortner","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2921-3494","authenticated-orcid":false,"given":"B","family":"Mayer","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Department of Pharmacology and Toxicology University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2004.05332.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201000564"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.108.5.435"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13349"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13354"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115818"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0008-6215(90)84096-D"},{"key":"e_1_2_10_9_1","first-page":"327","article-title":"Diastolic heart failure: a concise review","volume":"5","author":"Aziz F","year":"2013","journal-title":"J Clin Med Res"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02033207"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.07.026"},{"key":"e_1_2_10_12_1","first-page":"1380","article-title":"Isolation of 5\u2010hydroxymethylfurfural from cigarette smoke condensate","volume":"32","author":"Black DK","year":"1966","journal-title":"Chem Ind"},{"key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/S0022-5223(19)35984-7","article-title":"Diltiazem cardioplegia. 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