{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T18:01:26Z","timestamp":1788026486002,"version":"build-2784847793"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T00:00:00Z","timestamp":1645056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["105-2314-B-002-125-MY3 & 104-2314-B- 002-204"],"award-info":[{"award-number":["105-2314-B-002-125-MY3 & 104-2314-B- 002-204"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Myocardial dysfunction is a major cause of poor outcomes in the post-cardiac arrest period. Omecamtiv mecarbil (OM) is a selective small molecule activator of cardiac myosin that prolongs myocardial systole and increases stroke volume without apparent effects on myocardial oxygen demand. OM administration is safe and improves cardiac function in patients with acute heart failure. Whether OM improves post-resuscitation myocardial dysfunction remains unclear. This study investigated the effect of OM treatment on post-resuscitation myocardial dysfunction and outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      Adult male rats were resuscitated after 9.5 min of asphyxia-induced cardiac arrest. OM and normal saline was continuously intravenously infused after return of spontaneous circulation (ROSC) at 0.25 mg\/kg\/h for 4 h in the experimental group and control group, respectively (n = 20 in each group). Hemodynamic parameters were measured hourly and monitored for 4 h after cardiac arrest. Recovery of neurological function was evaluated by neurological functioning scores (0\u201312; favorable: 11\u201312) for rats 72 h after cardiac arrest. OM treatment prolonged left ventricular ejection time and improved post-resuscitation cardiac output. Post-resuscitation heart rate and left ventricular systolic function (dp\/dt\n                      <jats:sub>40<\/jats:sub>\n                      ) were not different between groups. Kaplan-Meier analysis showed non-statistically higher 72-h survival in the OM group (72.2% [13\/18] and 58.8% [10\/17], p = 0.386). The OM group had a higher chance of having favorable neurological outcomes in surviving rats 72 h after cardiac arrest (84.6% [11\/13] vs. 40% [4\/10], p = 0.026). The percentage of damaged neurons was lower in the OM group in a histology study at 72 h after cardiac arrest (55.5\u00b12.3% vs. 76.2\u00b110.2%, p = 0.004).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>OM treatment improved post-resuscitation myocardial dysfunction and neurological outcome in an animal model. These findings support further pre-clinical studies to improve outcomes in post-cardiac arrest care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0264165","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T13:45:18Z","timestamp":1645105518000},"page":"e0264165","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Omecamtiv mecarbil treatment improves post-resuscitation cardiac function and neurological outcome in a rat model"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1691-9057","authenticated-orcid":true,"given":"Shih-Ni","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Shan","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2981-4537","authenticated-orcid":true,"given":"Chien-Hua","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Jone","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,17]]},"reference":[{"key":"pone.0264165.ref001","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1161\/CIRCULATIONAHA.108.191259","article-title":"American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics\u2013 2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee","volume":"119","author":"D Lloyd-Jones","year":"2009","journal-title":"Circulation"},{"key":"pone.0264165.ref002","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.resuscitation.2011.03.024","article-title":"ROC Investigators. Cardiac arrest survival did not increase in the Resuscitation Outcomes Consortium after implementation of the 2005 AHA CPR and ECC guidelines","volume":"82","author":"BL Bigham","year":"2011","journal-title":"Resuscitation"},{"key":"pone.0264165.ref003","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1016\/S0735-1097(02)02594-9","article-title":"Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest","volume":"40","author":"I Laurent","year":"2002","journal-title":"J Am Coll Cardiol"},{"key":"pone.0264165.ref004","first-page":"350","article-title":"Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke","volume":"79","author":"JP Nolan","year":"2008","journal-title":"Resuscitation"},{"key":"pone.0264165.ref005","first-page":"145","article-title":"Minimizing hypoxic injury during cardiac arrest","volume":"5","author":"LB Becker","year":"1997","journal-title":"New Horiz"},{"key":"pone.0264165.ref006","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/0735-1097(96)00130-1","article-title":"Myocardial dysfunction after resuscitation from cardiac arrest: an example of global myocardial stunning","volume":"28","author":"KB Kern","year":"1996","journal-title":"J Am Coll Cardiol"},{"key":"pone.0264165.ref007","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1097\/00024382-200116001-00005","article-title":"Strategies to improve myocardial protection during extracorporeal circulation","volume":"16","author":"P. Menasche","year":"2001","journal-title":"Shock"},{"key":"pone.0264165.ref008","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.resuscitation.2005.01.012","article-title":"Reversible myocardial dysfunction after cardiopulmonary resuscitation","volume":"66","author":"M Ruiz-Bail\u00e9n","year":"2005","journal-title":"Resuscitation"},{"key":"pone.0264165.ref009","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1126\/science.1200113","article-title":"Cardiac myosin activation: a potential therapeutic approach for systolic heart failure","volume":"331","author":"FI Malik","year":"2011","journal-title":"Science"},{"key":"pone.0264165.ref010","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pharmthera.2012.03.002","article-title":"Novel therapies in acute and chronic heart failure","volume":"135","author":"D Aronson","year":"2012","journal-title":"Pharmacol Ther"},{"key":"pone.0264165.ref011","doi-asserted-by":"crossref","first-page":"212518","DOI":"10.7573\/dic.212518","article-title":"Cardiac myosin activators for heart failure therapy: focus on omecamtiv mecarbil","volume":"7","author":"E Kaplinsky","year":"2018","journal-title":"Drugs Context"},{"key":"pone.0264165.ref012","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/j.jacc.2016.01.031","article-title":"Acute Treatment With Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure: The ATOMIC-AHF Study","volume":"67","author":"JR Teerlink","year":"2016","journal-title":"J Am Coll Cardiol"},{"key":"pone.0264165.ref013","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s10741-009-9153-y","article-title":"Agents with inotropic properties for the management of acute heart failure syndromes. Traditional agents and beyond","volume":"14","author":"JR Teerlink","year":"2009","journal-title":"Heart Fail Rev"},{"key":"pone.0264165.ref014","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1097\/shk.0b013e31802f0218","article-title":"Erythropoietin improves the postresuscitation myocardial dysfunction and survival in the asphyxia-induced cardiac arrest model","volume":"28","author":"CH Huang","year":"2007","journal-title":"Shock"},{"key":"pone.0264165.ref015","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00395-015-0516-3","article-title":"Activation of mitochondrial STAT-3 and reduced mitochondria damage during hypothermia treatment for post-cardiac arrest myocardial dysfunction","volume":"110","author":"CH Huang","year":"2015","journal-title":"Basic Res Cardiol"},{"key":"pone.0264165.ref016","doi-asserted-by":"crossref","first-page":"e016139","DOI":"10.1161\/JAHA.120.016139","article-title":"Synergistic Effects of Moderate Therapeutic Hypothermia and Levosimendan on Cardiac Function and Survival After Asphyxia-Induced Cardiac Arrest in Rats","volume":"9","author":"CH Wang","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"pone.0264165.ref017","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1177\/0192623310389621","article-title":"Histology of the central nervous system","volume":"39","author":"RH Garman","year":"2011","journal-title":"Toxicol Pathol"},{"key":"pone.0264165.ref018","doi-asserted-by":"crossref","first-page":"e0166324","DOI":"10.1371\/journal.pone.0166324","article-title":"Urocortin Treatment Improves Acute Hemodynamic Instability and Reduces Myocardial Damage in Post-Cardiac Arrest Myocardial Dysfunction","volume":"11","author":"CH Huang","year":"2016","journal-title":"PLoS One"},{"key":"pone.0264165.ref019","doi-asserted-by":"crossref","first-page":"314796","DOI":"10.1155\/2015\/314796","article-title":"Myocardial Dysfunction and Shock after Cardiac Arrest","volume":"2015","author":"JC Jentzer","year":"2015","journal-title":"Biomed Res Int"},{"key":"pone.0264165.ref020","doi-asserted-by":"crossref","first-page":"3035","DOI":"10.1001\/jama.288.23.3035","article-title":"Resuscitation after cardiac arrest: a 3-phase time-sensitive model","volume":"288","author":"ML Weisfeldt","year":"2002","journal-title":"JAMA"},{"key":"pone.0264165.ref021","doi-asserted-by":"crossref","first-page":"S768","DOI":"10.1161\/CIRCULATIONAHA.110.971002","article-title":"American Heart Association. Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care","volume":"122","author":"MA Peberdy","year":"2010","journal-title":"Circulation"},{"key":"pone.0264165.ref022","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.1161\/01.CIR.95.12.2610","article-title":"Postresuscitation left ventricular systolic and diastolic dysfunction. Treatment with dobutamine","volume":"95","author":"KB Kern","year":"1997","journal-title":"Circulation"},{"key":"pone.0264165.ref023","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.resuscitation.2004.01.002","article-title":"Optimal dosing of dobutamine for treating post-resuscitation left ventricular dysfunction","volume":"61","author":"A Vasquez","year":"2004","journal-title":"Resuscitation"},{"key":"pone.0264165.ref024","doi-asserted-by":"crossref","first-page":"29060","DOI":"10.3390\/ijms161226147","article-title":"Use of Inotropic Agents in Treatment of Systolic Heart Failure","volume":"16","author":"S Tariq","year":"2015","journal-title":"Int J Mol Sci"},{"key":"pone.0264165.ref025","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1007\/s00134-013-3043-4","article-title":"Intensive care unit mortality after cardiac arrest: the relative contribution of shock and brain injury in a large cohort","volume":"39","author":"V Lemiale","year":"2013","journal-title":"Intensive Care Med"},{"key":"pone.0264165.ref026","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.resuscitation.2012.09.015","article-title":"The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest","volume":"84","author":"I Dragancea","year":"2013","journal-title":"Resuscitation"},{"key":"pone.0264165.ref027","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.resuscitation.2007.06.028","article-title":"Changes in cerebral blood flow and oxygen extraction during post-resuscitation syndrome","volume":"76","author":"V Lemiale","year":"2008","journal-title":"Resuscitation"},{"key":"pone.0264165.ref028","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/2110-5820-1-45","volume":"1","author":"N Mongardon","year":"2011","journal-title":"Ann Intensive Care"},{"key":"pone.0264165.ref029","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1136\/jnnp.2010.235218","article-title":"Hypoxic-ischaemic brain injury","volume":"11","author":"RS Howard","year":"2011","journal-title":"Pract Neurol"},{"key":"pone.0264165.ref030","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s00134-006-0442-9","article-title":"Postresuscitation myocardial dysfunction: correlated factors and prognostic implications","volume":"33","author":"WT Chang","year":"2007","journal-title":"Intensive Care Med"},{"key":"pone.0264165.ref031","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.resuscitation.2019.01.040","article-title":"Stenosis and revascularization of the coronary artery are associated with outcomes in presumed cardiogenic arrest survivors: A multi-center retrospective cohort study","volume":"137","author":"MS Tsai","year":"2019","journal-title":"Resuscitation"},{"key":"pone.0264165.ref032","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.resuscitation.2015.08.019","article-title":"Association of emergent and elective percutaneous coronary intervention with neurological outcome and survival after out-of-hospital cardiac arrest in patients with and without a history of heart disease","volume":"97","author":"MJ Kim","year":"2015","journal-title":"Resuscitation"},{"key":"pone.0264165.ref033","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.resuscitation.2017.12.004","article-title":"Early coronary angiography and percutaneous coronary intervention are associated with improved outcomes after out of hospital cardiac arrest","volume":"123","author":"JC Jentzer","year":"2018","journal-title":"Resuscitation"},{"key":"pone.0264165.ref034","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s10741-011-9255-1","article-title":"Pathophysiology and pathogenesis of post-resuscitation myocardial stunning","volume":"17","author":"A Chalkias","year":"2012","journal-title":"Heart Fail Rev"},{"key":"pone.0264165.ref035","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1161\/01.CIR.0000101925.37174.85","article-title":"Milrinone facilitates resuscitation from cardiac arrest and attenuates postresuscitation myocardial dysfunction","volume":"108","author":"JT Niemann","year":"2003","journal-title":"Circulation"},{"key":"pone.0264165.ref036","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.lab.2005.07.005","article-title":"Levosimendan improves postresuscitation outcomes in a rat model of CPR","volume":"146","author":"L Huang","year":"2005","journal-title":"J Lab Clin Med"},{"key":"pone.0264165.ref037","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.ajem.2008.05.004","article-title":"Combination pharmacotherapy in the treatment of experimental cardiac arrest","volume":"27","author":"T Xanthos","year":"2009","journal-title":"Am J Emerg Med"},{"key":"pone.0264165.ref038","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1007\/s11357-020-00171-7","article-title":"Aging alters acetylation status in skeletal and cardiac muscles","volume":"42","author":"D Yeo","year":"2020","journal-title":"Geroscience"},{"key":"pone.0264165.ref039","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0300-9572(97)01108-8","article-title":"Asphyxiation versus ventricular fibrillation cardiac arrest in dogs. Differences in cerebral resuscitation effects\u2014a preliminary study","volume":"35","author":"P Vaagenes","year":"1997","journal-title":"Resuscitation"},{"key":"pone.0264165.ref040","doi-asserted-by":"crossref","first-page":"e018657","DOI":"10.1161\/JAHA.120.018657","article-title":"Cardiac Arrest Induced by Asphyxia Versus Ventricular Fibrillation Elicits Comparable Early Changes in Cytokine Levels in the Rat Brain, Heart, and Serum","volume":"10","author":"T Uray","year":"2021","journal-title":"J Am Heart Assoc"},{"key":"pone.0264165.ref041","doi-asserted-by":"crossref","first-page":"e508","DOI":"10.1097\/CCM.0000000000003070","article-title":"University of Pittsburgh Post-Cardiac Arrest Service. Phenotyping Cardiac Arrest: Bench and Bedside Characterization of Brain and Heart Injury Based on Etiology","volume":"46","author":"T Uray","year":"2018","journal-title":"Crit Care Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0264165","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T03:10:03Z","timestamp":1674789003000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0264165"}},"subtitle":[],"editor":[{"given":"Vincenzo","family":"Lionetti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,2,17]]},"references-count":41,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0264165","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,17]]}}}