{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T14:28:39Z","timestamp":1768746519978,"version":"3.49.0"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2011,10,20]],"date-time":"2011-10-20T00:00:00Z","timestamp":1319068800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1002241","type":"journal-article","created":{"date-parts":[[2011,10,20]],"date-time":"2011-10-20T21:12:52Z","timestamp":1319145172000},"page":"e1002241","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["NHE Inhibition Does Not Improve Na+ or Ca2+ Overload During Reperfusion: Using Modeling to Illuminate the Mechanisms Underlying a Therapeutic Failure"],"prefix":"10.1371","volume":"7","author":[{"given":"Byron N.","family":"Roberts","sequence":"first","affiliation":[]},{"given":"David J.","family":"Christini","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2011,10,20]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1124\/pr.107.06002","article-title":"Interaction of cardiovascular risk factors with myocardial ischemia\/reperfusion injury, preconditioning, and postconditioning.","volume":"59","author":"P Ferdinandy","year":"2007","journal-title":"Pharmacol Rev"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1056\/NEJMra071667","article-title":"Myocardial reperfusion injury.","volume":"357","author":"DM Yellon","year":"2007","journal-title":"N Engl J Med"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.cardiores.2007.01.014","article-title":"Reperfusion injury in humans: a review of clinical trials on reperfusion injury inhibitory strategies.","volume":"74","author":"MT Dirksen","year":"2007","journal-title":"Cardiovasc Res"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ijcard.2004.04.013","article-title":"Myocardial ischemia\/reperfusion-injury, a clinical view on a complex pathophysiological process.","volume":"100","author":"AL Moens","year":"2005","journal-title":"Int J Cardiol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1161\/01.RES.52.4.442","article-title":"Resting membrane potential, extracellular potassium activity, and intracellular sodium activity during acute global ischemia in isolated perfused guinea pig hearts.","volume":"52","author":"AG Kleber","year":"1983","journal-title":"Circ Res"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"H3036","DOI":"10.1152\/ajpheart.00771.2007","article-title":"The balance between inactivation and activation of the na+-k+ pump underlies the triphasic accumulation of extracellular k+ during myocardial ischemia.","volume":"293","author":"JR Terkildsen","year":"2007","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1161\/01.RES.70.2.409","article-title":"Early changes in extracellular potassium in ischemic rabbit myocardium. the role of extracellular carbon dioxide accumulation and diffusion.","volume":"70","author":"WE Cascio","year":"1992","journal-title":"Circ Res"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"3074","DOI":"10.1529\/biophysj.105.070557","article-title":"A dynamic model of excitation-contraction coupling during acidosis in cardiac ventricular myocytes.","volume":"90","author":"EJ Crampin","year":"2006","journal-title":"Biophys J"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"H400","DOI":"10.1152\/ajpheart.00502.2004","article-title":"Contrasting effects of ischemia on the kinetics of membrane voltage and intracellular calcium transient underlie electrical alternans.","volume":"288","author":"V Lakireddy","year":"2005","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1093\/cvr\/28.9.1312","article-title":"Acidosis and arrhythmias in cardiac muscle.","volume":"28","author":"CH Orchard","year":"1994","journal-title":"Cardiovasc Res"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"C967","DOI":"10.1152\/ajpcell.1990.258.6.C967","article-title":"Effects of changes of ph on the contractile function of cardiac muscle.","volume":"258","author":"CH Orchard","year":"1990","journal-title":"Am J Physiol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1161\/01.RES.50.2.310","article-title":"The effect of ph on the transient-state kinetics of ca2+-mg2+-atpase of cardiac sarcoplasmic reticulum. a comparison with skeletal sarcoplasmic reticulum.","volume":"50","author":"F Mandel","year":"1982","journal-title":"Circ Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1016\/j.bpj.2008.11.045","article-title":"A thermodynamic model of the cardiac sar-coplasmic\/endoplasmic ca(2+) (serca) pump.","volume":"96","author":"K Tran","year":"2009","journal-title":"Biophys J"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1161\/01.RES.79.6.1100","article-title":"Regulation of cardiac ca2+ release channel (ryanodine receptor) by ca2+, h+, mg2+, and adenine nucleotides under normal and simulated ischemic conditions.","volume":"79","author":"L Xu","year":"1996","journal-title":"Circ Res"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1113\/jphysiol.1993.sp019730","article-title":"The mechanism by which cytoplasmic protons inhibit the sodium-calcium exchanger in guinea-pig heart cells.","volume":"466","author":"AE Doering","year":"1993","journal-title":"J Physiol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/j.amjcard.2010.10.004","article-title":"Cme multimedia activity: Mechanisms and consequences of cardiac ischemia-reperfusion injury: Insights and evidence to improve outcomes.","volume":"106","author":"RA Gottlieb","year":"2010","journal-title":"Am J Cardiol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1161\/01.RES.85.9.777","article-title":"The myocardial na(+)- h(+) exchange: structure, regulation, and its role in heart disease.","volume":"85","author":"M Karmazyn","year":"1999","journal-title":"Circ Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S0079-6107(98)00023-6","article-title":"Modelling myocardial ischaemia and reperfusion.","volume":"69","author":"FF Ch'en","year":"1998","journal-title":"Prog Biophys Mol Biol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"3324","DOI":"10.1016\/S0006-3495(01)75965-6","article-title":"Ionic charge conservation and long-term steady state in the luo-rudy dynamic cell model.","volume":"81","author":"TJ Hund","year":"2001","journal-title":"Biophys J"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1006\/jtbi.1997.0487","article-title":"A conservation principle and its e_ect on the formulation of na-ca exchanger current in cardiac cells.","volume":"189","author":"A Varghese","year":"1997","journal-title":"J Theor Biol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s002490050254","article-title":"A theory for the membrane potential of living cells.","volume":"29","author":"LP Endresen","year":"2000","journal-title":"Eur Biophys J"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1113\/jphysiol.1990.sp018221","article-title":"Extracellular h+ inactivation of na(+)-h+ exchange in the sheep cardiac purkinje fibre.","volume":"428","author":"RD Vaughan-Jones","year":"1990","journal-title":"J Physiol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1139\/o02-157","article-title":"Role of bicarbonate in the regulation of intracellular ph in the mammalian ventricular myocyte.","volume":"80","author":"RD Vaughan-Jones","year":"2002","journal-title":"Biochem Cell Biol"},{"key":"ref24","first-page":"557","article-title":"Atp regulates cardiac ca2+ channel activity via a mechanism independent of protein phosphorylation.","volume":"433","author":"K Yazawa","year":"1997","journal-title":"Pugers Arch"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1126\/science.1321495","article-title":"Phosphorylation-independent modulation of l-type calcium channels by magnesium-nucleotide complexes.","volume":"257","author":"B O'Rourke","year":"1992","journal-title":"Science"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1529\/biophysj.104.046284","article-title":"Modeling regulation of cardiac katp and l-type ca2+ currents by atp, adp, and mg2+.","volume":"88","author":"A Michailova","year":"2005","journal-title":"Biophys J"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1161\/CIRCRESAHA.109.202267","article-title":"Contributions of ion channel currents to ventricular action potential changes and induction of early afterdepolarizations during acute hypoxia.","volume":"105","author":"N Gaur","year":"2009","journal-title":"Circ Res"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1161\/01.CIR.72.4.922","article-title":"Effect of serial brief ischemic episodes on extracellular k+, ph, and activation in the pig.","volume":"72","author":"WF Fleet","year":"1985","journal-title":"Circulation"},{"key":"ref29","first-page":"H2071","article-title":"Temporary acidosis during reperfusion limits myocardial infarct size in dogs.","volume":"272","author":"M Kitakaze","year":"1997","journal-title":"Am J Physiol"},{"key":"ref30","first-page":"H1236","article-title":"Osmotic shock: modulation of contractile function, phi, and ischemic damage in perfused guinea pig heart.","volume":"276","author":"DE Befroy","year":"1999","journal-title":"Am J Physiol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1161\/01.CIR.92.8.2266","article-title":"Pharmacological evidence for the persistent activation of atp-sensitive k+ channels in early phase of reperfusion and its protective role against myocardial stunning.","volume":"92","author":"S Shigematsu","year":"1995","journal-title":"Circulation"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0014-2999(01)01514-X","article-title":"Differences in protective profiles of diltiazem isomers in ischemic and reperfused guinea pig hearts.","volume":"434","author":"R Sato","year":"2002","journal-title":"Eur J Pharmacol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"H2398","DOI":"10.1152\/ajpheart.2001.281.6.H2398","article-title":"Blocking na(+)\/h(+) exchange reduces [na(+)](i) and [ca(2+)](i) load after ischemia and improves function in intact hearts.","volume":"281","author":"J An","year":"2001","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/S0008-6363(02)00656-9","article-title":"Intracellular na+ regulation in cardiac myocytes.","volume":"57","author":"DM Bers","year":"2003","journal-title":"Cardiovasc Res"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.yjmcc.2008.01.005","article-title":"The role of nhe-1 in myocardial hypertrophy and remodelling.","volume":"44","author":"M Karmazyn","year":"2008","journal-title":"J Mol Cell Cardiol"},{"key":"ref36","first-page":"26","article-title":"Effects of the na+\/h+-exchange inhibitor hoe 642 on intracellular ph, calcium and sodium in isolated rat ventricular myocytes.","volume":"433","author":"U Russ","year":"1996","journal-title":"Pugers Arch"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/978-1-60327-360-2_25","article-title":"Atp-loaded liposomes for targeted treatment in models of myocardial ischemia.","volume":"605","author":"TS Levchenko","year":"2010","journal-title":"Methods Mol Biol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1161\/01.RES.60.2.153","article-title":"Myocardial contractile function during ischemia and hypoxia.","volume":"60","author":"DG Allen","year":"1987","journal-title":"Circ Res"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.yjmcc.2010.06.012","article-title":"Role of mitochondrial dysfunction in cardiac glycoside toxicity.","volume":"49","author":"T Liu","year":"2010","journal-title":"J Mol Cell Cardiol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1161\/01.RES.51.5.614","article-title":"Interaction of acidosis and increased extracellular potassium on action potential characteristics and conduction in guinea pig ventricular muscle.","volume":"51","author":"Y Kagiyama","year":"1982","journal-title":"Circ Res"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/S0008-6363(97)00093-X","article-title":"Electrophysiologic effects of acute myocardial ischemia: a theoretical study of altered cell excitability and action potential duration.","volume":"35","author":"RM Shaw","year":"1997","journal-title":"Cardiovasc Res"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1161\/01.RES.59.3.348","article-title":"Intra- and extracellular actions of proton on the calcium current of isolated guinea pig ventricular cells.","volume":"59","author":"H Irisawa","year":"1986","journal-title":"Circ Res"},{"key":"ref43","first-page":"H977","article-title":"Effect of acidosis on ca2+ uptake and release by sarcoplasmic reticulum of intact rat ventricular myocytes.","volume":"275","author":"JT Hulme","year":"1998","journal-title":"Am J Physiol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"3527","DOI":"10.1172\/JCI25371","article-title":"The mitochondrial origin of postischemic arrhythmias.","volume":"115","author":"FG Akar","year":"2005","journal-title":"J Clin Invest"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1161\/01.RES.77.1.153","article-title":"Arrhythmia and delayed recovery of cardiac action potential during reperfusion after ischemia. role of oxygen radical-induced no-reow phenomenon.","volume":"77","author":"EA Aiello","year":"1995","journal-title":"Circ Res"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002241","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T23:25:56Z","timestamp":1713050756000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002241"}},"subtitle":[],"editor":[{"given":"Andrew D.","family":"McCulloch","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2011,10,20]]},"references-count":45,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2011,10,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1002241","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,10,20]]}}}