Selecting heart failure patients for metabolic interventions

References

• Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the heart failure association (HFA) of the ESC. Eur J Heart Fail. 2016;18:891–975.
   PubMed Web of Science ®Google Scholar
• Udelson JE, Stevenson LW. The future of heart failure diagnosis, therapy, and management. Circulation. 2016;133:2671–2686.
   PubMed Web of Science ®Google Scholar
• Mozaffarian D, Benjamin EJ, Go AS, et al. Executive summary: heart disease and stroke statistics–2016 update: a report from the American heart association. Circulation. 2016;133:447–454.
   PubMed Web of Science ®Google Scholar
• McMurray JJV, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004.
   PubMed Web of Science ®Google Scholar
• Gheorghiade M, Larson CJ, Shah SJ, et al. Developing new treatments for heart failure: focus on the heart. Circ Heart Fail. 2016;9:e002727.
   Web of Science ®Google Scholar
• Bers DM. Cardiac excitation-contraction coupling. Nature. 2002;415:198–205.
   PubMed Web of Science ®Google Scholar
• Westenbrink BD, Edwards AG, McCulloch AD, et al. The promise of CaMKII inhibition for heart disease: preventing heart failure and arrhythmias. Expert Opin Ther Targets. 2013;17:889–903.
   PubMed Web of Science ®Google Scholar
• Mudd JO, Kass DA. Tackling heart failure in the twenty-first century. Nature. 2008;451:919–928.
   PubMed Web of Science ®Google Scholar
• Shah AM, Mann DL. In search of new therapeutic targets and strategies for heart failure: recent advances in basic science. Lancet Lond Engl. 2011;378:704–712.
   PubMed Web of Science ®Google Scholar
• Westenbrink BD, Ling H, Divakaruni AS, et al. Mitochondrial reprogramming induced by CaMKIIδ mediates hypertrophy decompensation. Circ Res. 2015;116:e28–e39.
   PubMed Web of Science ®Google Scholar
• Neubauer S. The failing heart–an engine out of fuel. N Engl J Med. 2007;356:1140–1151.
   PubMed Web of Science ®Google Scholar
• Hasenfuss G. Alterations of calcium-regulatory proteins in heart failure. Cardiovasc Res. 1998;37:279–289.
   PubMed Web of Science ®Google Scholar
• Greenberg B, Butler J, Felker GM, et al. Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial. Lancet Lond Engl. 2016;387:1178–1186.
   PubMed Web of Science ®Google Scholar
• Herrmann G, Decherd G. The chemical nature of heart failure. Ann Intern Med. 1939;12:1233–1244.
   Google Scholar
• Stanley WC, Recchia FA, Lopaschuk GD. Myocardial substrate metabolism in the normal and failing heart. Physiol Rev. 2005;85:1093–1129.
   PubMed Web of Science ®Google Scholar
• Ardehali H, Sabbah HN, Burke MA, et al. Targeting myocardial substrate metabolism in heart failure: potential for new therapies. Eur J Heart Fail. 2012;14:120–129.
   PubMed Web of Science ®Google Scholar
• Doehner W, Frenneaux M, Anker SD. Metabolic impairment in heart failure: the myocardial and systemic perspective. J Am Coll Cardiol. 2014;64:1388–1400.
   PubMed Web of Science ®Google Scholar
• Akhmedov AT, Rybin V, Marín-García J. Mitochondrial oxidative metabolism and uncoupling proteins in the failing heart. Heart Fail Rev. 2015;20:227–249.
   PubMed Web of Science ®Google Scholar
• Sorokina N, O’Donnell JM, McKinney RD, et al. Recruitment of compensatory pathways to sustain oxidative flux with reduced carnitine palmitoyltransferase I activity characterizes inefficiency in energy metabolism in hypertrophied hearts. Circulation. 2007;115:2033–2041.
   PubMed Web of Science ®Google Scholar
• Schroeder MA, Lau AZ, Chen AP, et al. Hyperpolarized (13)C magnetic resonance reveals early- and late-onset changes to in vivo pyruvate metabolism in the failing heart. Eur J Heart Fail. 2013;15:130–140.
   PubMed Web of Science ®Google Scholar
• Alexander D, Lombardi R, Rodriguez G, et al. Metabolomic distinction and insights into the pathogenesis of human primary dilated cardiomyopathy. Eur J Clin Invest. 2011;41:527–538.
   PubMed Web of Science ®Google Scholar
• Fillmore N, Lopaschuk GD. Targeting mitochondrial oxidative metabolism as an approach to treat heart failure. Biochim Biophys Acta. 2013;1833:857–865.
   PubMed Web of Science ®Google Scholar
• Kim J, Tchernyshyov I, Semenza GL, et al. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006;3:177–185.
   PubMed Web of Science ®Google Scholar
• Aubert G, Martin OJ, Horton JL, et al. The failing heart relies on ketone bodies as a fuel. Circulation. 2016;133:698–705.
   PubMed Web of Science ®Google Scholar
• Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell. 2005;120:483–495.
   PubMed Web of Science ®Google Scholar
• Kohlhaas M, Maack C. Interplay of defective excitation-contraction coupling, energy starvation, and oxidative stress in heart failure. Trends Cardiovasc Med. 2011;21:69–73.
   PubMed Web of Science ®Google Scholar
• Ide T, Tsutsui H, Hayashidani S, et al. Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction. Circ Res. 2001;88:529–535.
   PubMed Web of Science ®Google Scholar
• Galougahi KK, Liu -C-C, Gentile C, et al. Glutathionylation mediates angiotensin II-induced eNOS uncoupling, amplifying NADPH oxidase-dependent endothelial dysfunction. J Am Heart Assoc. 2014;3:e000731.
   Web of Science ®Google Scholar
• Lijnen PJ, van Pelt JF, Fagard RH. Downregulation of manganese superoxide dismutase by angiotensin II in cardiac fibroblasts of rats: association with oxidative stress in myocardium. Am J Hypertens. 2010;23:1128–1135.
   PubMed Web of Science ®Google Scholar
• Daiber A. Redox signaling (cross-talk) from and to mitochondria involves mitochondrial pores and reactive oxygen species. Biochim Biophys Acta. 2010;1797:897–906.
   PubMed Web of Science ®Google Scholar
• Paulus WJ, Tschöpe C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol. 2013;62:263–271.
   PubMed Web of Science ®Google Scholar
• Casademont J, Miró O. Electron transport chain defects in heart failure. Heart Fail Rev. 2002;7:131–139.
   PubMedGoogle Scholar
• Aimo A, Borrelli C, Vergaro G, et al. Targeting mitochondrial dysfunction in chronic heart failure: current evidence and potential approaches. Curr Pharm Des. 2016 ;22:4807-4822.
   PubMed Web of Science ®Google Scholar
• Joiner M-LA, Koval OM, Li J, et al. CaMKII determines mitochondrial stress responses in heart. Nature. 2012;491:269–273.
   PubMed Web of Science ®Google Scholar
• Oka T, Hikoso S, Yamaguchi O, et al. Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature. 2012;485:251–255.
   PubMed Web of Science ®Google Scholar
• Dai D-F, Chen T, Szeto H, et al. Mitochondrial targeted antioxidant peptide ameliorates hypertensive cardiomyopathy. J Am Coll Cardiol. 2011;58:73–82.
   PubMed Web of Science ®Google Scholar
• Yancey DM, Guichard JL, Ahmed MI, et al. Cardiomyocyte mitochondrial oxidative stress and cytoskeletal breakdown in the heart with a primary volume overload. Am J Physiol Heart Circ Physiol. 2015;308:H651–H663.
   PubMed Web of Science ®Google Scholar
• Long Q, Yang K, Yang Q. Regulation of mitochondrial ATP synthase in cardiac pathophysiology. Am J Cardiovasc Dis. 2015;5:19–32.
   PubMed Web of Science ®Google Scholar
• García-Bermúdez J, Sánchez-Aragó M, Soldevilla B, et al. PKA phosphorylates the ATPase inhibitory factor 1 and inactivates its capacity to bind and inhibit the mitochondrial H(+)-ATP synthase. Cell Rep. 2015;12:2143–2155.
   PubMed Web of Science ®Google Scholar
• Wang S-B, Murray CI, Chung HS, et al. Redox regulation of mitochondrial ATP synthase. Trends Cardiovasc Med. 2013;23:14–18.
   PubMed Web of Science ®Google Scholar
• Beer M, Seyfarth T, Sandstede J, et al. Absolute concentrations of high-energy phosphate metabolites in normal, hypertrophied, and failing human myocardium measured noninvasively with (31)P-SLOOP magnetic resonance spectroscopy. J Am Coll Cardiol. 2002;40:1267–1274.
   PubMed Web of Science ®Google Scholar
• Carley AN, Taegtmeyer H, Lewandowski ED. Matrix revisited: mechanisms linking energy substrate metabolism to the function of the heart. Circ Res. 2014;114:717–729.
   PubMed Web of Science ®Google Scholar
• Cornelissen VA, Defoor JGM, Stevens A, et al. Effect of creatine supplementation as a potential adjuvant therapy to exercise training in cardiac patients: a randomized controlled trial. Clin Rehabil. 2010;24:988–999.
   PubMed Web of Science ®Google Scholar
• Carvalho APPF, Rassi S, Fontana KE, et al. Influence of creatine supplementation on the functional capacity of patients with heart failure. Arq Bras Cardiol. 2012;99:623–629.
   PubMed Web of Science ®Google Scholar
• Lygate CA, Aksentijevic D, Dawson D, et al. Living without creatine: unchanged exercise capacity and response to chronic myocardial infarction in creatine-deficient mice. Circ Res. 2013;112:945–955.
   PubMed Web of Science ®Google Scholar
• Aquilani R, Opasich C, Gualco A, et al. Adequate energy-protein intake is not enough to improve nutritional and metabolic status in muscle-depleted patients with chronic heart failure. Eur J Heart Fail. 2008;10:1127–1135.
   PubMed Web of Science ®Google Scholar
• Ahmad T, Kelly JP, McGarrah RW, et al. Prognostic implications of long-chain acylcarnitines in heart failure and reversibility with mechanical circulatory support. J Am Coll Cardiol. 2016;67:291–299.
   PubMed Web of Science ®Google Scholar
• Hunter WG, Kelly JP, McGarrah RW, et al. Metabolomic profiling identifies novel circulating biomarkers of mitochondrial dysfunction differentially elevated in heart failure with preserved versus reduced ejection fraction: evidence for shared metabolic impairments in clinical heart failure. J Am Heart Assoc. 2016;5:e003190.
   Web of Science ®Google Scholar
• Obrzut S, Tiongson J, Jamshidi N, et al. Assessment of metabolic phenotypes in patients with non-ischemic dilated cardiomyopathy undergoing cardiac resynchronization therapy. J Cardiovasc Transl Res. 2010;3:643–651.
   PubMed Web of Science ®Google Scholar
• Ho E, Karimi Galougahi K, Liu -C-C, et al. Biological markers of oxidative stress: applications to cardiovascular research and practice. Redox Biol. 2013;1:483–491.
   PubMed Web of Science ®Google Scholar
• Tang WHW, Wang Z, Fan Y, et al. Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: refining the gut hypothesis. J Am Coll Cardiol. 2014;64:1908–1914.
   PubMed Web of Science ®Google Scholar
• Roul D, Recchia FA. Metabolic alterations induce oxidative stress in diabetic and failing hearts: different pathways, same outcome. Antioxid Redox Signal. 2015;22:1502–1514.
   PubMed Web of Science ®Google Scholar
• Sun A, Zou Y, Wang P, et al. Mitochondrial aldehyde dehydrogenase 2 plays protective roles in heart failure after myocardial infarction via suppression of the cytosolic JNK/p53 pathway in mice. J Am Heart Assoc. 2014;3:e000779.
   PubMed Web of Science ®Google Scholar
• Landar A, Zmijewski JW, Dickinson DA, et al. Interaction of electrophilic lipid oxidation products with mitochondria in endothelial cells and formation of reactive oxygen species. Am J Physiol Heart Circ Physiol. 2006;290:H1777–87.
   PubMed Web of Science ®Google Scholar
• Srivastava S, Chandrasekar B, Bhatnagar A, et al. Lipid peroxidation-derived aldehydes and oxidative stress in the failing heart: role of aldose reductase. Am J Physiol Heart Circ Physiol. 2002;283:H2612–9.
   PubMed Web of Science ®Google Scholar
• Salonen JT, Nyyssönen K, Salonen R, et al. Lipoprotein oxidation and progression of carotid atherosclerosis. Circulation. 1997;95:840–845.
   PubMed Web of Science ®Google Scholar
• Banne AF, Amiri A, Pero RW. Reduced level of serum thiols in patients with a diagnosis of active disease. J Anti-Aging Med. 2003;6:327–334.
   PubMedGoogle Scholar
• Chung HS, Wang S-B, Venkatraman V, et al. Cysteine oxidative posttranslational modifications: emerging regulation in the cardiovascular system. Circ Res. 2013;112:382–392.
   PubMed Web of Science ®Google Scholar
• Patel RS, Ghasemzadeh N, Eapen DJ, et al. Novel biomarker of oxidative stress is associated with risk of death in patients with coronary artery disease. Circulation. 2016;133:361–369.
   PubMed Web of Science ®Google Scholar
• Turell L, Radi R, Alvarez B. The thiol pool in human plasma: the central contribution of albumin to redox processes. Free Radic Biol Med. 2013;65:244–253.
   PubMed Web of Science ®Google Scholar
• Belch JJ, Bridges AB, Scott N, et al. Oxygen free radicals and congestive heart failure. Br Heart J. 1991;65:245–248.
   PubMedGoogle Scholar
• Kundi H, Ates I, Kiziltunc E, et al. A novel oxidative stress marker in acute myocardial infarction; thiol/disulphide homeostasis. Am J Emerg Med. 2015;33:1567–1571.
   PubMed Web of Science ®Google Scholar
• Go Y-M, Jones DP. Cysteine/cystine redox signaling in cardiovascular disease. Free Radic Biol Med. 2011;50:495–509.
   PubMed Web of Science ®Google Scholar
• Koning AM, Meijers WC, Pasch A, et al. Serum free thiols in chronic heart failure. Pharmacol Res. 2016;111:452–458.
   PubMed Web of Science ®Google Scholar
• Massion PB, Feron O, Dessy C, et al. Nitric oxide and cardiac function: ten years after, and continuing. Circ Res. 2003;93:388–398.
   PubMed Web of Science ®Google Scholar
• Silberman GA, Fan T-HM, Liu H, et al. Uncoupled cardiac nitric oxide synthase mediates diastolic dysfunction. Circulation. 2010;121:519–528.
   PubMed Web of Science ®Google Scholar
• Figueira TR, Barros MH, Camargo AA, et al. Mitochondria as a source of reactive oxygen and nitrogen species: from molecular mechanisms to human health. Antioxid Redox Signal. 2013;18:2029–2074.
   PubMed Web of Science ®Google Scholar
• Winlaw DS, Smythe GA, Keogh AM, et al. Increased nitric oxide production in heart failure. Lancet Lond Engl. 1994;344:373–374.
   PubMed Web of Science ®Google Scholar
• Osorio JC, Xu X, Vogel T, et al. Plasma nitrate accumulation during the development of pacing-induced dilated cardiac myopathy in conscious dogs is due to renal impairment. Nitric Oxide Biol Chem Off J Nitric Oxide Soc. 2001;5:7–17.
   PubMed Web of Science ®Google Scholar
• Polhemus DJ, Lefer DJ. Emergence of hydrogen sulfide as an endogenous gaseous signaling molecule in cardiovascular disease. Circ Res. 2014;114:730–737.
   PubMed Web of Science ®Google Scholar
• Parenica J, Kala P, Pavkova MG, et al. Natriuretic peptides, nitrite/nitrate and superoxide dismutase have additional value on top of the GRACE score in prediction of one-year mortality and rehospitalisation for heart failure in STEMI patients - Multiple biomarkers prospective cohort study. Int J Cardiol. 2016;211:96–104.
   PubMed Web of Science ®Google Scholar
• van den Berg E, Pasch A, Westendorp WH, et al. Urinary sulfur metabolites associate with a favorable cardiovascular risk profile and survival benefit in renal transplant recipients. J Am Soc Nephrol JASN. 2014;25(6):1303–1312.
   PubMed Web of Science ®Google Scholar
• Papadimitriou L, Smith-Jones PM, Sarwar CMS, et al. Utility of positron emission tomography for drug development for heart failure. Am Heart J. 2016;175:142–152.
   PubMed Web of Science ®Google Scholar
• Nakatani K, Watabe T, Masuda D, et al. Myocardial energy provision is preserved by increased utilization of glucose and ketone bodies in CD36 knockout mice. Metabolism. 2015;64:1165–1174.
   PubMed Web of Science ®Google Scholar
• Cannon MV, Silljé HHW, Sijbesma JWA, et al. Cardiac LXRα protects against pathological cardiac hypertrophy and dysfunction by enhancing glucose uptake and utilization. EMBO Mol Med. 2015;7:1229–1243.
   PubMed Web of Science ®Google Scholar
• Dávila-Román VG, Vedala G, Herrero P, et al. Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 2002;40:271–277.
   PubMed Web of Science ®Google Scholar
• Slart RHJA, Tio RA, van der Vleuten PA, et al. Myocardial perfusion reserve and contractile pattern after beta-blocker therapy in patients with idiopathic dilated cardiomyopathy. J Nucl Cardiol Off Publ Am Soc Nucl Cardiol. 2010;17:479–485.
   PubMed Web of Science ®Google Scholar
• Nielsen R, Jorsal A, Iversen P, et al. Heart failure patients with prediabetes and newly diagnosed diabetes display abnormalities in myocardial metabolism. J Nucl Cardiol Off Publ Am Soc Nucl Cardiol. 2016. DOI: 10.1007/s12350-016-0622-0.
   Google Scholar
• van Campen CMC, Visser FC, van der Weerdt AP, et al. FDG PET as a predictor of response to resynchronisation therapy in patients with ischaemic cardiomyopathy. Eur J Nucl Med Mol Imaging. 2007;34:309–315.
   PubMed Web of Science ®Google Scholar
• Winter JL, Castro PF, Quintana JC, et al. Effects of trimetazidine in nonischemic heart failure: a randomized study. J Card Fail. 2014;20:149–154.
   PubMed Web of Science ®Google Scholar
• Handley MG, Medina RA, Nagel E, et al. PET imaging of cardiac hypoxia: opportunities and challenges. J Mol Cell Cardiol. 2011;51:640–650.
   PubMed Web of Science ®Google Scholar
• Scherer DJ, Psaltis PJ. Future imaging of atherosclerosis: molecular imaging of coronary atherosclerosis with (18)F positron emission tomography. Cardiovasc Diagn Ther. 2016;6:354–367.
   PubMed Web of Science ®Google Scholar
• Medina RA, Mariotti E, Pavlovic D, et al. 64Cu-CTS: a promising radiopharmaceutical for the identification of low-grade cardiac hypoxia by PET. J Nucl Med Off Publ Soc Nucl Med. 2015;56:921–926.
   PubMed Web of Science ®Google Scholar
• Carroll VN, Truillet C, Shen B, et al. (11)C.Ascorbic and (11)C.dehydroascorbic acid, an endogenous redox pair for sensing reactive oxygen species using positron emission tomography. Chem Commun Camb Engl. 2016;52:4888–4890.
   PubMed Web of Science ®Google Scholar
• Huang X, Gao Y, Qin J, et al. The role of miR-34a in the hepatoprotective effect of hydrogen sulfide on ischemia/reperfusion injury in young and old rats. Lesnefsky EJ, editor. Plos ONE. 2014;9:e113305.
   PubMed Web of Science ®Google Scholar
• Bizino MB, Hammer S, Lamb HJ. Metabolic imaging of the human heart: clinical application of magnetic resonance spectroscopy. Heart Br Card Soc. 2014;100:881–890.
   Google Scholar
• Levelt E, Rodgers CT, Clarke WT, et al. Cardiac energetics, oxygenation, and perfusion during increased workload in patients with type 2 diabetes mellitus. Eur Heart J. 2015. DOI: 10.1093/eurheartj/ehv42.
   PubMed Web of Science ®Google Scholar
• Fragasso G, Perseghin G, De Cobelli F, et al. Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphate ratio in patients with heart failure. Eur Heart J. 2006;27:942–948.
   PubMed Web of Science ®Google Scholar
• Dass S, Holloway CJ, Cochlin LE, et al. No evidence of myocardial oxygen deprivation in nonischemic heart failure. Circ Heart Fail. 2015;8:1088–1093.
   PubMed Web of Science ®Google Scholar
• Schroeder MA, Clarke K, Neubauer S, et al. Hyperpolarized magnetic resonance: a novel technique for the in vivo assessment of cardiovascular disease. Circulation. 2011;124:1580–1594.
   PubMed Web of Science ®Google Scholar
• Westenbrink BD, Dorn GW. Imaging the cardiac diet. Eur J Heart Fail. 2013;15:123–124.
   PubMed Web of Science ®Google Scholar
• Josan S, Park JM, Hurd R, et al. In vivo investigation of cardiac metabolism in the rat using MRS of hyperpolarized 1-13C. and 2-13C.pyruvate. NMR Biomed. 2013;26:1680–1687.
   PubMed Web of Science ®Google Scholar
• Bersin RM, Wolfe C, Kwasman M, et al. Improved hemodynamic function and mechanical efficiency in congestive heart failure with sodium dichloroacetate. J Am Coll Cardiol. 1994;23:1617–1624.
   PubMed Web of Science ®Google Scholar
• Wilson JR, Mancini DM, Ferraro N, et al. Effect of dichloroacetate on the exercise performance of patients with heart failure. J Am Coll Cardiol. 1988;12:1464–1469.
   PubMed Web of Science ®Google Scholar
• Home PD, Pocock SJ, Beck-Nielsen H, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet Lond Engl. 2009;373:2125–2135.
   PubMed Web of Science ®Google Scholar
• Holubarsch CJF, Rohrbach M, Karrasch M, et al. A double-blind randomized multicentre clinical trial to evaluate the efficacy and safety of two doses of etomoxir in comparison with placebo in patients with moderate congestive heart failure: the ERGO (etomoxir for the recovery of glucose oxidation) study. Clin Sci Lond Engl. 1979;2007(113):205–212.
   Google Scholar
• Goszcz K, Deakin SJ, Duthie GG, et al. Antioxidants in cardiovascular therapy: panacea or false hope? front. Cardiovasc Med. 2015;2:29.
   Google Scholar
• Aitio M-L. N-acetylcysteine – passe-partout or much ado about nothing? Br J Clin Pharmacol. 2006;61:5–15.
   PubMed Web of Science ®Google Scholar
• Ye Y, Li J, Yuan Z. Effect of antioxidant vitamin supplementation on cardiovascular outcomes: a meta-analysis of randomized controlled trials. Plos One. 2013;8:e56803.
   PubMed Web of Science ®Google Scholar
• Tamariz L, Hare JM. Xanthine oxidase inhibitors in heart failure: where do we go from here? Circulation. 2015;131:1741–1744.
   PubMed Web of Science ®Google Scholar
• Atkuri KR, Mantovani JJ, Herzenberg LA, et al. N-Acetylcysteine–a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol. 2007;7:355–359.
   PubMed Web of Science ®Google Scholar
• Dröge W. Aging-related changes in the thiol/disulfide redox state: implications for the use of thiol antioxidants. Exp Gerontol. 2002;37:1333–1345.
   PubMed Web of Science ®Google Scholar
• Chatzianastasiou A, Bibli S-I, Andreadou I, et al. Cardioprotection by H2S donors: nitric oxide-dependent and -independent mechanisms. J Pharmacol Exp Ther. 2016;358:431–440.
   PubMed Web of Science ®Google Scholar
• Gibson CM, Giugliano RP, Kloner RA, et al. EMBRACE STEMI study: a Phase 2a trial to evaluate the safety, tolerability, and efficacy of intravenous MTP-131 on reperfusion injury in patients undergoing primary percutaneous coronary intervention. Eur Heart J. 2016;37:1296–1303.
   PubMed Web of Science ®Google Scholar