{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:46:52Z","timestamp":1790484412323,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T00:00:00Z","timestamp":1649980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>The use of zebrafish to explore cardiac physiology has been widely adopted within the scientific community. Whether this animal model can be used to determine drug cardiac toxicity via electrocardiogram (ECG) analysis is still an ongoing question. Several reports indicate that the recording configuration severely affects the ECG waveforms and its derived-parameters, emphasizing the need for improved characterization. To address this problem, we recorded ECGs from adult zebrafish hearts in three different configurations (unexposed heart, exposed heart, and extracted heart) to identify the most reliable method to explore ECG recordings at baseline and in response to commonly used clinical therapies. We found that the exposed heart configuration provided the most reliable and reproducible ECG recordings of waveforms and intervals. We were unable to determine T wave morphology in unexposed hearts. In extracted hearts, ECG intervals were lengthened and P waves were unstable. However, in the exposed heart configuration, we were able to reliably record ECGs and subsequently establish the QT-RR relationship (Holzgrefe correction) in response to changes in heart rate.<\/jats:p>","DOI":"10.3390\/biology11040603","type":"journal-article","created":{"date-parts":[[2022,4,16]],"date-time":"2022-04-16T07:42:41Z","timestamp":1650094961000},"page":"603","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Effect of Hypothermia and Osmotic Shock on the Electrocardiogram of Adult Zebrafish"],"prefix":"10.3390","volume":"11","author":[{"given":"Elodie","family":"Arel","sequence":"first","affiliation":[{"name":"PhyMedExp, Universit\u00e9 de Montpellier, Inserm U1046, UMR CNRS 9412, 34090 Montpellier, France"},{"name":"Institut de g\u00e9nomique fonctionnelle (IGF), Universit\u00e9 de Montpellier, Inserm U1191, UMR CNRS 5203, 34094 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1261-3384","authenticated-orcid":false,"given":"Laura","family":"Rolland","sequence":"additional","affiliation":[{"name":"Institut de g\u00e9nomique fonctionnelle (IGF), Universit\u00e9 de Montpellier, Inserm U1191, UMR CNRS 5203, 34094 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Thireau","sequence":"additional","affiliation":[{"name":"PhyMedExp, Universit\u00e9 de Montpellier, Inserm U1046, UMR CNRS 9412, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1721-6564","authenticated-orcid":false,"given":"Angelo Giovanni","family":"Torrente","sequence":"additional","affiliation":[{"name":"Institut de g\u00e9nomique fonctionnelle (IGF), Universit\u00e9 de Montpellier, Inserm U1191, UMR CNRS 5203, 34094 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Bechard","sequence":"additional","affiliation":[{"name":"PhyMedExp, Universit\u00e9 de Montpellier, Inserm U1046, UMR CNRS 9412, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Bride","sequence":"additional","affiliation":[{"name":"PhyMedExp, Universit\u00e9 de Montpellier, Inserm U1046, UMR CNRS 9412, 34090 Montpellier, France"},{"name":"Institut de g\u00e9nomique fonctionnelle (IGF), Universit\u00e9 de Montpellier, Inserm U1191, UMR CNRS 5203, 34094 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0950-0063","authenticated-orcid":false,"given":"Chris","family":"Jopling","sequence":"additional","affiliation":[{"name":"Institut de g\u00e9nomique fonctionnelle (IGF), Universit\u00e9 de Montpellier, Inserm U1191, UMR CNRS 5203, 34094 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4777-0654","authenticated-orcid":false,"given":"Marie","family":"Demion","sequence":"additional","affiliation":[{"name":"PhyMedExp, Universit\u00e9 de Montpellier, Inserm U1046, UMR CNRS 9412, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Yves","family":"Le Guennec","sequence":"additional","affiliation":[{"name":"PhyMedExp, Universit\u00e9 de Montpellier, Inserm U1046, UMR CNRS 9412, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"H269","DOI":"10.1152\/ajpheart.00960.2005","article-title":"In Vivo Recording of Adult Zebrafish Electrocardiogram and Assessment of Drug-Induced QT Prolongation","volume":"291","author":"Milan","year":"2006","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11316","DOI":"10.1073\/pnas.0702724104","article-title":"Zebrafish Model for Human Long QT Syndrome","volume":"104","author":"Arnaout","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.vascn.2013.01.007","article-title":"Optimization of the Adult Zebrafish ECG Method for Assessment of Drug-Induced QTc Prolongation","volume":"67","author":"Chaudhari","year":"2013","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"25073","DOI":"10.1038\/srep25073","article-title":"Improvement of Surface ECG Recording in Adult Zebrafish Reveals That the Value of This Model Exceeds Our Expectation","volume":"6","author":"Liu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15986","DOI":"10.1038\/s41598-018-33577-7","article-title":"Development of a Rapid and Economic in Vivo Electrocardiogram Platform for Cardiovascular Drug Assay and Electrophysiology Research in Adult Zebrafish","volume":"8","author":"Lin","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"607860","DOI":"10.3389\/fphys.2020.607860","article-title":"Adult and Developing Zebrafish as Suitable Models for Cardiac Electrophysiology and Pathology in Research and Industry","volume":"11","author":"Echeazarra","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.yjmcc.2009.08.034","article-title":"Adult Zebrafish Heart as a Model for Human Heart? An Electrophysiological Study","volume":"48","author":"Nemtsas","year":"2010","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.bbrc.2008.06.109","article-title":"Characterization of Isolated Ventricular Myocytes from Adult Zebrafish (Danio rerio)","volume":"374","author":"Brette","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.vascn.2013.05.004","article-title":"Preclinical QT Safety Assessment: Cross-Species Comparisons and Human Translation from an Industry Consortium","volume":"69","author":"Holzgrefe","year":"2014","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1136\/hrt.2004.057307","article-title":"The Normal ECG in Childhood and Adolescence","volume":"91","author":"Dickinson","year":"2005","journal-title":"Heart Br. Card. Soc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"E12","DOI":"10.3171\/foc.2007.22.5.13","article-title":"Medical Management of Cerebral Edema","volume":"22","author":"Raslan","year":"2007","journal-title":"Neurosurg. Focus"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Dabrowski, W., Siwicka-Gieroba, D., Robba, C., Badenes, R., Bialy, M., Iwaniuk, P., Schlegel, T.T., and Jaroszynski, A. (2020). Plasma Hyperosmolality Prolongs QTc Interval and Increases Risk for Atrial Fibrillation in Traumatic Brain Injury Patients. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051293"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Dabrowski, W., Siwicka-Gieroba, D., Robba, C., Bielacz, M., So\u0142ek-Pastuszka, J., Kotfis, K., Bohatyrewicz, R., Jaroszy\u0144ski, A., Malbrain, M.L.N.G., and Badenes, R. (2021). Potentially Detrimental Effects of Hyperosmolality in Patients Treated for Traumatic Brain Injury. J. Clin. Med., 10.","DOI":"10.3390\/jcm10184141"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1093\/europace\/eup376","article-title":"QTc Prolongation during Therapeutic Hypothermia: Are We Giving It the Attention It Deserves?","volume":"12","author":"Khan","year":"2010","journal-title":"EP Europace"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.jcrc.2017.02.030","article-title":"The Effect of Targeted Temperature Management on QT and Corrected QT Intervals in Patients with Cardiac Arrest","volume":"39","author":"Rosol","year":"2017","journal-title":"J. Crit. Care"},{"key":"ref_16","first-page":"353","article-title":"An Analysis of the Time-Relations of Electrocardiograms","volume":"7","author":"Bazett","year":"1920","journal-title":"Heart"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Br\u00f6nnimann, D., Djukic, T., Triet, R., Dellenbach, C., Saveljic, I., Rieger, M., Rohr, S., Filipovic, N., and Djonov, V. (2016). Pharmacological Modulation of Hemodynamics in Adult Zebrafish In Vivo. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150948"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4283","DOI":"10.1109\/JSEN.2019.2897789","article-title":"Acquisition, Processing and Analysis of Electrocardiogram in Awake Zebrafish","volume":"19","author":"Le","year":"2019","journal-title":"IEEE Sens. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/j.chemosphere.2018.09.014","article-title":"Toxic Responses of Zebrafish (Danio Rerio) to Thallium and Deltamethrin Characterized in the Electrocardiogram","volume":"212","author":"Song","year":"2018","journal-title":"Chemosphere"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1093\/cvr\/cvaa238","article-title":"Adult Zebrafish Ventricular Electrical Gradients as Tissue Mechanisms of ECG Patterns under Baseline vs. Oxidative Stress","volume":"117","author":"Zhao","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1007\/s10439-010-9993-6","article-title":"Electrocardiogram Signals to Assess Zebrafish Heart Regeneration: Implication of Long QT Intervals","volume":"38","author":"Yu","year":"2010","journal-title":"Ann. Biomed. Eng."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Chablais, F., Veit, J., Rainer, G., and Ja\u017awi\u0144ska, A. (2011). The Zebrafish Heart Regenerates after Cryoinjury-Induced Myocardial Infarction. BMC Dev. Biol., 11.","DOI":"10.1186\/1471-213X-11-21"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1089\/zeb.2014.1016","article-title":"Hemodynamics and Ventricular Function in a Zebrafish Model of Injury and Repair","volume":"11","author":"Lee","year":"2014","journal-title":"Zebrafish"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhang, X., Tai, J., Park, J., and Tai, Y.-C. (2014, January 26\u201330). Flexible MEA for Adult Zebrafish ECG Recording Covering Both Ventricle and Atrium. Proceedings of the 2014 IEEE 27th International Conference on Micro Electro Mechanical Systems (MEMS), San Francisco, CA, USA.","DOI":"10.1109\/MEMSYS.2014.6765772"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lenning, M., Fortunato, J., Le, T., Clark, I., Sherpa, A., Yi, S., Hofsteen, P., Thamilarasu, G., Yang, J., and Xu, X. (2017). Real-Time Monitoring and Analysis of Zebrafish Electrocardiogram with Anomaly Detection. Sensors, 18.","DOI":"10.3390\/s18010061"},{"key":"ref_26","first-page":"61","article-title":"In Vivo Surface Electrocardiography for Adult Zebrafish","volume":"18","author":"Zhao","year":"2019","journal-title":"J. Vis. Exp. JoVE"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1007\/s10439-009-9668-3","article-title":"Micro-Electrocardiograms to Study Post-Ventricular Amputation of Zebrafish Heart","volume":"37","author":"Sun","year":"2009","journal-title":"Ann. Biomed. Eng."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.bios.2015.04.027","article-title":"Flexible and Waterproof Micro-Sensors to Uncover Zebrafish Circadian Rhythms: The next Generation of Cardiac Monitoring for Drug Screening","volume":"71","author":"Zhang","year":"2015","journal-title":"Biosens. Bioelectron."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s10544-011-9612-9","article-title":"Flexible Microelectrode Arrays to Interface Epicardial Electrical Signals with Intracardial Calcium Transients in Zebrafish Hearts","volume":"14","author":"Yu","year":"2012","journal-title":"Biomed. Microdevices"},{"key":"ref_30","first-page":"789","article-title":"Wearable Multi-Channel Microelectrode Membranes for Elucidating Electrophysiological Phenotypes of Injured Myocardium","volume":"6","author":"Cao","year":"2014","journal-title":"Integr. Biol. Quant. Biosci. Nano Macro"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.bbrc.2011.03.121","article-title":"Reconstitution of Defective Protein Trafficking Rescues Long-QT Syndrome in Zebrafish","volume":"408","author":"Meder","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1016\/j.cca.2011.07.002","article-title":"In-Vitro Recording of Adult Zebrafish Heart Electrocardiogram\u2014A Platform for Pharmacological Testing","volume":"412","author":"Tsai","year":"2011","journal-title":"Clin. Chim. Acta Int. J. Clin. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"H676","DOI":"10.1152\/ajpheart.00330.2016","article-title":"Zebrafish Heart as a Model to Study the Integrative Autonomic Control of Pacemaker Function","volume":"311","author":"Stoyek","year":"2016","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1242\/jeb.02117","article-title":"Development of the Sympatho-Vagal Balance in the Cardiovascular System in Zebrafish (Danio rerio) Characterized by Power Spectrum and Classical Signal Analysis","volume":"209","author":"Schwerte","year":"2006","journal-title":"J. Exp. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Stoyek, M.R., Hortells, L., and Quinn, T.A. (2021). From Mice to Mainframes: Experimental Models for Investigation of the Intracardiac Nervous System. J. Cardiovasc. Dev. Dis., 8.","DOI":"10.3390\/jcdd8110149"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1111\/bph.13391","article-title":"The High Frequency Relationship: Implications for Torsadogenic HERG Blockers","volume":"173","author":"Champeroux","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.1111\/bph.14354","article-title":"High-Frequency Autonomic Modulation: A New Model for Analysis of Autonomic Cardiac Control","volume":"175","author":"Fesler","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/nature08899","article-title":"Zebrafish Heart Regeneration Occurs by Cardiomyocyte Dedifferentiation and Proliferation","volume":"464","author":"Jopling","year":"2010","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1007\/s00018-019-03343-7","article-title":"MiR-182-5p Is an Evolutionarily Conserved Tbx5 Effector That Impacts Cardiac Development and Electrical Activity in Zebrafish","volume":"77","author":"Guzzolino","year":"2020","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.bbamem.2003.08.016","article-title":"Sodium and Chloride Transport in Soft Water and Hard Water Acclimated Zebrafish (Danio rerio)","volume":"1618","author":"Boisen","year":"2003","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e62386","DOI":"10.7554\/eLife.62386","article-title":"Osmolarity-Independent Electrical Cues Guide Rapid Response to Injury in Zebrafish Epidermis","volume":"9","author":"Kennard","year":"2020","journal-title":"eLife"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/emp2.12104","article-title":"Electrocardiographic Changes in Patients Undergoing Targeted Temperature Management","volume":"1","author":"Jandu","year":"2020","journal-title":"J. Am. Coll. Emerg. Physicians Open"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1161\/CIRCULATIONAHA.107.752220","article-title":"Deficient Zebrafish Ether-\u00e0-Go-Go-Related Gene Channel Gating Causes Short-QT Syndrome in Zebrafish Reggae Mutants","volume":"117","author":"Hassel","year":"2008","journal-title":"Circulation"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cbpc.2015.03.007","article-title":"The Effects of Cocaine on Heart Rate and Electrocardiogram in Zebrafish (Danio rerio)","volume":"172\u2013173","author":"Mersereau","year":"2015","journal-title":"Comp. Biochem. Physiol. Toxicol. Pharmacol. CBP"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4780","DOI":"10.1038\/s41598-018-23129-4","article-title":"Baseline MRNA Expression Differs Widely between Common Laboratory Strains of Zebrafish","volume":"8","author":"Holden","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"dmm048827","DOI":"10.1242\/dmm.048827","article-title":"Development and Optimization of an In Vivo Electrocardiogram Recording Method and Analysis Program for Adult Zebrafish","volume":"14","author":"Duong","year":"2021","journal-title":"Dis. Model. Mech."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/11\/4\/603\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:54:57Z","timestamp":1760136897000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/11\/4\/603"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,15]]},"references-count":46,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["biology11040603"],"URL":"https:\/\/doi.org\/10.3390\/biology11040603","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,15]]}}}