{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T13:26:37Z","timestamp":1751030797577},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Am J Cardiovasc Drugs"],"published-print":{"date-parts":[[2021,11]]},"DOI":"10.1007\/s40256-021-00474-w","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T04:15:48Z","timestamp":1616386548000},"page":"589-593","update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Treating Acute Decompensated Heart Failure in Patients with COVID-19 Using Intravenous Nitroglycerin in 5% Glutathione"],"prefix":"10.1007","volume":"21","author":[{"given":"Wayne","family":"Kaesemeyer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsiana","family":"Suvorava","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"issue":"12","key":"474_CR1","doi-asserted-by":"publisher","first-page":"2238","DOI":"10.1002\/ejhf.2052","volume":"22","author":"D Tomasoni","year":"2020","unstructured":"Tomasoni D, Inciardi RM, Lombardi CM, Tedino C, Agostoni P, Ameri P, et al. Impact of heart failure on the clinical course and outcomes of patients hospitalized for COVID-19. Results of the Cardio-COVID-Italy multicentre study. Eur J Heart Fail. 2020;22(12):2238\u201347.","journal-title":"Eur J Heart Fail."},{"key":"474_CR2","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.13158","author":"G Doolub","year":"2021","unstructured":"Doolub G, Wong C, Hewitson L, Mohamed A, Todd F, Gogola L, et al. Impact of COVID-19 on inpatient referral of acute heart failure: a single-centre experience from the south-west of the UK. ESC Heart Fail. 2021. https:\/\/doi.org\/10.1002\/ehf2.13158.","journal-title":"ESC Heart Fail."},{"issue":"12","key":"474_CR3","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1002\/ejhf.1990","volume":"22","author":"JR Rey","year":"2020","unstructured":"Rey JR, Caro-Codon J, Rosillo SO, Iniesta AM, Castrejon-Castrejon S, Marco-Clement I, et al. Heart failure in COVID-19 patients: prevalence, incidence and prognostic implications. Eur J Heart Fail. 2020;22(12):2205\u201315.","journal-title":"Eur J Heart Fail."},{"issue":"1","key":"474_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/FJC.0000000000000932","volume":"77","author":"T Suvorava","year":"2021","unstructured":"Suvorava T, Kaesemeyer W. Targeting the vascular endothelium in the treatment of COVID-19. J Cardiovasc Pharmacol. 2021;77(1):1\u20133.","journal-title":"J Cardiovasc Pharmacol."},{"issue":"1","key":"474_CR5","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1002\/ehf2.13083","volume":"8","author":"K Matsushita","year":"2021","unstructured":"Matsushita K, Marchandot B, Carmona A, Curtiaud A, El Idrissi A, Trimaille A, et al. Increased susceptibility to SARS-CoV-2 infection in patients with reduced left ventricular ejection fraction. ESC Heart Fail. 2021;8(1):380\u20139.","journal-title":"ESC Heart Fail."},{"issue":"6","key":"474_CR6","doi-asserted-by":"publisher","first-page":"e137","DOI":"10.1161\/CIR.0000000000000509","volume":"136","author":"CW Yancy","year":"2017","unstructured":"Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, et al. 2017 ACC\/AHA\/HFSA Focused Update of the 2013 ACCF\/AHA guideline for the management of heart failure: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136(6):e137\u201361.","journal-title":"Circulation"},{"issue":"4","key":"474_CR7","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1177\/107424840400900403","volume":"9","author":"U Elkayam","year":"2004","unstructured":"Elkayam U, Bitar F, Akhter MW, Khan S, Patrus S, Derakhshani M. Intravenous nitroglycerin in the treatment of decompensated heart failure: potential benefits and limitations. J Cardiovasc Pharmacol Ther. 2004;9(4):227\u201341.","journal-title":"J Cardiovasc Pharmacol Ther"},{"issue":"15","key":"474_CR8","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/0165-6147(94)90319-0","volume":"1994","author":"BM Bennett","year":"1994","unstructured":"Bennett BM, McDonald BJ, Nigam R, Simon WC. Biotransformation of organic nitrates and vascular smooth muscle cell function. Trends PharmacolSci. 1994;1994(15):245\u20139.","journal-title":"Trends PharmacolSci."},{"key":"474_CR9","doi-asserted-by":"publisher","first-page":"8306","DOI":"10.1073\/pnas.122225199","volume":"99","author":"Z Chen","year":"2002","unstructured":"Chen Z, Zhang J, Stamler JS. Identification of the enzymatic mechanism of nitroglycerin bioactivation. Proc Natl Acad Sci USA. 2002;99:8306\u201311.","journal-title":"Proc Natl Acad Sci USA"},{"key":"474_CR10","first-page":"43","volume":"6","author":"DD Stewart","year":"1888","unstructured":"Stewart DD. Remarkable tolerance to nitroglycerin. Phila Polyclin. 1888;6:43.","journal-title":"Phila Polyclin"},{"key":"474_CR11","doi-asserted-by":"publisher","first-page":"2338","DOI":"10.1161\/hc4401.098432","volume":"104","author":"D Kim","year":"2001","unstructured":"Kim D, Rybalkin SD, Pi X, Wang Y, Zhang C, Munzel T, et al. Upregulation of phosphodiesterase 1A1 expression is associated with the development of nitrate tolerance. Circulation. 2001;104:2338\u201343.","journal-title":"Circulation"},{"issue":"1\u20132","key":"474_CR12","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/0014-2999(96)00505-5","volume":"313","author":"L De Garavilla","year":"1996","unstructured":"De Garavilla L, Pagani ED, Buchholz RA, Dundore R, Bode DC, Volberg ML, et al. Zaprinast, but not dipyridamole, reverses hemodynamic tolerance to nitroglycerin in vivo. Eur J Pharmacol. 1996;313(1\u20132):89\u201396.","journal-title":"Eur J Pharmacol"},{"issue":"13","key":"474_CR13","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1056\/NEJM198709243171304","volume":"317","author":"M Packer","year":"1987","unstructured":"Packer M, Lee WH, Kessler PD, Gottlieb SS, Medina N, Yushak M. Prevention and reversal of nitrate tolerance in patients with congestive heart failure. N Engl J Med. 1987;317(13):799\u2013804.","journal-title":"N Engl J Med"},{"issue":"3","key":"474_CR14","first-page":"297","volume":"42","author":"RA Yeates","year":"1992","unstructured":"Yeates RA, Schmid M. Total prevention of the development of in vitro tolerance to organic nitrates. Experiments with antioxidants. Arzneim Forsch. 1992;42(3):297\u2013302.","journal-title":"Arzneim Forsch"},{"key":"474_CR15","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1161\/01.RES.0000184694.03262.6d","volume":"97","author":"T Munzel","year":"2005","unstructured":"Munzel T, Daiber A, Mulsch A. Explaining the phenomenon of nitrate tolerance. Circ Res. 2005;97:618\u201328.","journal-title":"Circ Res"},{"issue":"11","key":"474_CR16","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1089\/ars.2015.6376","volume":"23","author":"A Daiber","year":"2015","unstructured":"Daiber A, Munzel T. Organic nitrate therapy, nitrate tolerance, and nitrate-induced endothelial dysfunction: emphasis on redox biology and oxidative stress. Antioxid Redox Signal. 2015;23(11):899\u2013942.","journal-title":"Antioxid Redox Signal"},{"key":"474_CR17","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1172\/JCI117637","volume":"95","author":"T M\u00fcnzel","year":"1995","unstructured":"M\u00fcnzel T, Sayegh H, Freeman BA, Tarpey MM, Harrison DG. Evidence for enhanced vascular superoxide anion production in nitrate tolerance. A novel mechanism underlying tolerance and cross-tolerance. J Clin Investig. 1995;95:187\u201394.","journal-title":"J Clin Investig"},{"issue":"23","key":"474_CR18","doi-asserted-by":"publisher","first-page":"2299","DOI":"10.1161\/01.CIR.97.23.2299","volume":"97","author":"K Kugiyama","year":"1998","unstructured":"Kugiyama K, Ohgushi M, Motoyama T, Hirashima O, Soejima H, Misumi K, et al. Intracoronary infusion of reduced glutathione improves endothelial vasomotor response to acetylcholine in human coronary circulation. Circulation. 1998;97(23):2299\u2013301.","journal-title":"Circulation"},{"issue":"123","key":"474_CR19","doi-asserted-by":"publisher","first-page":"338","DOI":"10.7326\/0003-4819-123-5-199509010-00003","volume":"1995","author":"D Giugliano","year":"1995","unstructured":"Giugliano D, Marfella R, Verrazzo G, Acampora R, Donzella C, Quatraro A, et al. Abnormal rheologic effects of glyceryl trinitrate in patients with non-insulin-dependent diabetes mellitus and reversal by antioxidants. Ann Intern Med. 1995;1995(123):338\u201343.","journal-title":"Ann Intern Med"},{"issue":"2","key":"474_CR20","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1385\/CT:6:2:131","volume":"6","author":"L Wang","year":"2006","unstructured":"Wang L, Yang Y, Dwivedi S, Xu Y, Chu ET, Li J, et al. Manipulating glutathione-S-transferases may prevent the development of tolerance to nitroglycerin. Cardiovasc Toxicol. 2006;6(2):131\u201344.","journal-title":"Cardiovasc Toxicol"},{"issue":"10","key":"474_CR21","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1161\/01.RES.0000250430.62775.99","volume":"99","author":"JV Esplugues","year":"2006","unstructured":"Esplugues JV, Rocha M, Nunez C, Bosca I, Ibiza S, Herance JR, et al. Complex I dysfunction and tolerance to nitroglycerin: an approach based on mitochondrial-targeted antioxidants. Circ Res. 2006;99(10):1067\u201375.","journal-title":"Circ Res"},{"issue":"5","key":"474_CR22","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1038\/sj.bjp.0703665","volume":"131","author":"WH Kaesemeyer","year":"2000","unstructured":"Kaesemeyer WH, Ogonowski AA, Jin L, Caldwell RB, Caldwell RW. Endothelial nitric oxide synthase is a site of superoxide synthesis in endothelial cells treated with glyceryl trinitrate. Br J Pharmacol. 2000;131(5):1019\u201323.","journal-title":"Br J Pharmacol"},{"issue":"11","key":"474_CR23","doi-asserted-by":"publisher","first-page":"8893","DOI":"10.1074\/jbc.M110.190017","volume":"286","author":"M Oelze","year":"2011","unstructured":"Oelze M, Knorr M, Schell R, Kamuf J, Pautz A, Art J, et al. Regulation of human mitochondrial aldehyde dehydrogenase (ALDH-2) activity by electrophiles in vitro. J Biol Chem. 2011;286(11):8893\u2013900.","journal-title":"J Biol Chem"},{"issue":"1","key":"474_CR24","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1074\/jbc.M606477200","volume":"282","author":"P Wenzel","year":"2007","unstructured":"Wenzel P, Hink U, Oelze M, Schuppan S, Schaeuble K, Schildknecht S, et al. Role of reduced lipoic acid in the redox regulation of mitochondrial aldehyde dehydrogenase (ALDH-2) activity. Implications for mitochondrial oxidative stress and nitrate tolerance. J Biol Chem. 2007;282(1):792\u20139.","journal-title":"J Biol Chem"},{"key":"474_CR25","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1124\/jpet.103.056119","volume":"308","author":"G Abou-Mohamed","year":"2004","unstructured":"Abou-Mohamed G, Johnson JA, Jin L, El Remessy AB, Do K, Kaesemeyer WH, et al. Roles of superoxide, peroxynitrite, and protein kinase C in the development of tolerance to nitroglycerin. J Pharmacol Exp Ther. 2004;308:289\u201399.","journal-title":"J Pharmacol Exp Ther"},{"key":"474_CR26","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1172\/JCI200419267","volume":"113","author":"K Sydow","year":"2004","unstructured":"Sydow K, Daiber A, Oelze M, Chen Z, August M, Wendt M, et al. Central role of mitochondrial aldehyde dehydrogenase and reactive oxygen species in nitroglycerin tolerance and cross-tolerance. J Clin Investig. 2004;113:482\u20139.","journal-title":"J Clin Investig."},{"issue":"25","key":"474_CR27","doi-asserted-by":"publisher","first-page":"8569","DOI":"10.1073\/pnas.0708615105","volume":"105","author":"MG Bonini","year":"2008","unstructured":"Bonini MG, Stadler K, Silva SO, Corbett J, Dore M, Petranka J, et al. Constitutive nitric oxide synthase activation is a significant route for nitroglycerin-mediated vasodilation. Proc Natl Acad Sci USA. 2008;105(25):8569\u201374.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"7","key":"474_CR28","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1111\/j.1476-5381.2012.01876.x","volume":"166","author":"SM Khong","year":"2012","unstructured":"Khong SM, Andrews KL, Huynh NN, Venardos K, Aprico A, Michell DL, et al. Arginase II inhibition prevents nitrate tolerance. Br J Pharmacol. 2012;166(7):2015\u201323.","journal-title":"Br J Pharmacol."},{"key":"474_CR29","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/sj.bjp.0703293","volume":"130","author":"G Abou-Mohamed","year":"2000","unstructured":"Abou-Mohamed G, Kaesemeyer WH, Caldwell RB, Caldwell RW. Role of l-arginine in the vascular actions and development of tolerance to nitroglycerin. Br J Pharmacol. 2000;130:211\u20138.","journal-title":"Br J Pharmacol"},{"issue":"8","key":"474_CR30","doi-asserted-by":"publisher","first-page":"e104101","DOI":"10.1371\/journal.pone.0104101","volume":"9","author":"M Mao","year":"2014","unstructured":"Mao M, Varadarajan S, Fukai T, Bakhshi FR, Chernaya O, Dudley SC Jr, et al. Nitroglycerin tolerance in caveolin-1 deficient mice. PLoS ONE. 2014;9(8):e104101.","journal-title":"PLoS ONE"},{"issue":"4","key":"474_CR31","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1016\/S0735-1097(10)80343-2","volume":"16","author":"M Packer","year":"1990","unstructured":"Packer M. What causes tolerance to nitroglycerin? The 100 year old mystery continues. J Am Coll Cardiol. 1990;16(4):932\u20135.","journal-title":"J Am Coll Cardiol."},{"issue":"2","key":"474_CR32","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1111\/bcp.12301","volume":"78","author":"T Johal","year":"2014","unstructured":"Johal T, Lees CC, Everett TR, Wilkinson IB. The nitric oxide pathway and possible therapeutic options in pre-eclampsia. Br J Clin Pharmacol. 2014;78(2):244\u201357.","journal-title":"Br J Clin Pharmacol."},{"key":"474_CR33","unstructured":"Diagnosing Adult Growth Hormone Deficiency, https:\/\/ClinicalTrials.gov\/show\/NCT03018886, Accessed: 04 December 2020. https:\/\/ClinicalTrials.gov\/show\/NCT03018886."},{"issue":"2","key":"474_CR34","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.taap.2006.01.003","volume":"212","author":"AP Rolo","year":"2006","unstructured":"Rolo AP, Palmeira CM. Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress. Toxicol Appl Pharmacol. 2006;212(2):167\u201378.","journal-title":"Toxicol Appl Pharmacol"},{"issue":"8","key":"474_CR35","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1038\/s41577-020-0368-4","volume":"20","author":"A Cavounidis","year":"2020","unstructured":"Cavounidis A, Mann EH. SARS-CoV-2 has a sweet tooth. Nat Rev Immunol. 2020;20(8):460.","journal-title":"Nat Rev Immunol"}],"container-title":["American Journal of Cardiovascular Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40256-021-00474-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40256-021-00474-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40256-021-00474-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T03:14:07Z","timestamp":1636341247000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40256-021-00474-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,22]]},"references-count":35,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["474"],"URL":"https:\/\/doi.org\/10.1007\/s40256-021-00474-w","relation":{},"ISSN":["1175-3277","1179-187X"],"issn-type":[{"value":"1175-3277","type":"print"},{"value":"1179-187X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,22]]},"assertion":[{"value":"6 March 2021","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No external funding was used in the preparation of this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Wayne Kaesemeyer and Tatsiana Suvorava declare that they have no potential conflicts of interest that might be relevant to the contents of this article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Not applicable.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of data and material"}},{"value":"Not applicable.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}},{"value":"Both authors contributed to the writing and revising of this Current Opinion article.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 contributions"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}