{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T21:37:42Z","timestamp":1785015462005,"version":"3.55.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T00:00:00Z","timestamp":1667174400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T00:00:00Z","timestamp":1667174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Decreased heart rate variability (HRV) may be a biomarker of brain injury severity in neonatal hypoxic-ischemic encephalopathy for which therapeutic hypothermia is standard treatment. While therapeutic hypothermia may influence the degree of brain injury; hypothermia may also affect HRV per se and obscure a potential association between HRV and hypoxic-ischemic encephalopathy. Previous results are conflicting. This study aimed to investigate the effect of hypothermia on HRV in healthy, anaesthetised, newborn piglets. Six healthy newborn piglets were anaesthetised. Three piglets were first kept normothermic (38.5\u201339.0\u00a0\u00b0C) for 3\u00a0h, then exposed to hypothermia (33.5\u201334.5\u00a0\u00b0C) for 3\u00a0h. Three piglets were first exposed to hypothermia for 3\u00a0h, then rewarmed to normothermia for 3\u00a0h. Temperature and ECG were recorded continuously. HRV was calculated from the ECG in 5\u00a0min epochs and included time domain and frequency domain variables. The HRV variables were compared between hypothermia and normothermia. All assessed HRV variables were higher during hypothermia compared to normothermia. Heart rate was lower during hypothermia compared to normothermia and all HRV variables correlated with heart rate. Hypothermia was associated with an increase in HRV; this could be mediated by bradycardia during hypothermia.<\/jats:p>","DOI":"10.1038\/s41598-022-22426-3","type":"journal-article","created":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T11:02:46Z","timestamp":1667214166000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Hypothermia and heart rate variability in a healthy newborn piglet model"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1120-5370","authenticated-orcid":false,"given":"Mette Vesterg\u00e5rd","family":"Pedersen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted Carl Kejlberg","family":"Andelius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah Brog\u00e5rd","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasper Jacobsen","family":"Kyng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tine Brink","family":"Henriksen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,31]]},"reference":[{"issue":"Suppl 1","key":"22426_CR1","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/pr.2013.206","volume":"74","author":"AC Lee","year":"2013","unstructured":"Lee, A. C. et al. Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990. Pediatr. Res. 74(Suppl 1), 50\u201372. https:\/\/doi.org\/10.1038\/pr.2013.206 (2013).","journal-title":"Pediatr. Res."},{"key":"22426_CR2","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.siny.2010.05.007","volume":"15","author":"L Bennet","year":"2010","unstructured":"Bennet, L., Booth, L. & Gunn, A. J. Potential biomarkers for hypoxic-ischemic encephalopathy. Semin. Fetal Neonatal. Med. 15, 253\u2013260. https:\/\/doi.org\/10.1016\/j.siny.2010.05.007 (2010).","journal-title":"Semin. Fetal Neonatal. Med."},{"key":"22426_CR3","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1161\/01.CIR.93.5.1043","volume":"93","author":"AJ Camm","year":"1996","unstructured":"Camm, A. J. et al. Heart rate variability: Standards of measurement, physiological interpretation and clinical use. Task force of the European society of cardiology and the North American society of pacing and electrophysiology. Circulation 93, 1043\u20131065 (1996).","journal-title":"Circulation"},{"key":"22426_CR4","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1186\/s12887-019-1603-7","volume":"19","author":"M Andersen","year":"2019","unstructured":"Andersen, M., Andelius, T. C. K., Pedersen, M. V., Kyng, K. J. & Henriksen, T. B. Severity of hypoxic ischemic encephalopathy and heart rate variability in neonates: A systematic review. BMC Pediatr. 19, 242. https:\/\/doi.org\/10.1186\/s12887-019-1603-7 (2019).","journal-title":"BMC Pediatr."},{"key":"22426_CR5","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1159\/000493002","volume":"115","author":"V Oliveira","year":"2019","unstructured":"Oliveira, V. et al. Prognostic accuracy of heart rate variability analysis in neonatal encephalopathy: A systematic review. Neonatology 115, 59\u201367. https:\/\/doi.org\/10.1159\/000493002 (2019).","journal-title":"Neonatology"},{"key":"22426_CR6","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-020-03882-3","author":"I Bersani","year":"2020","unstructured":"Bersani, I. et al. Heart rate variability as possible marker of brain damage in neonates with hypoxic ischemic encephalopathy: A systematic review. Eur. J. Pediatr. https:\/\/doi.org\/10.1007\/s00431-020-03882-3 (2020).","journal-title":"Eur. J. Pediatr."},{"key":"22426_CR7","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1038\/pr.2015.28","volume":"77","author":"RM Goulding","year":"2015","unstructured":"Goulding, R. M. et al. Heart rate variability in hypoxic ischemic encephalopathy: Correlation with EEG grade and 2-y neurodevelopmental outcome. Pediatr. Res. 77, 681\u2013687. https:\/\/doi.org\/10.1038\/pr.2015.28 (2015).","journal-title":"Pediatr. Res."},{"key":"22426_CR8","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1055\/s-0033-1361937","volume":"31","author":"BD Vergales","year":"2014","unstructured":"Vergales, B. D. et al. Depressed heart rate variability is associated with abnormal EEG, MRI, and death in neonates with hypoxic ischemic encephalopathy. Am. J. Perinatol. 31, 855\u2013862. https:\/\/doi.org\/10.1055\/s-0033-1361937 (2014).","journal-title":"Am. J. Perinatol."},{"key":"22426_CR9","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1007\/s12098-012-0703-2","volume":"79","author":"D Aliefendio\u011flu","year":"2012","unstructured":"Aliefendio\u011flu, D., Do\u011fru, T., Albayrak, M., Dibekm\u0131s\u0131rl\u0131o\u011flu, E. & Sanl\u0131, C. Heart rate variability in neonates with hypoxic ischemic encephalopathy. Indian J. Pediatr. 79, 1468\u20131472. https:\/\/doi.org\/10.1007\/s12098-012-0703-2 (2012).","journal-title":"Indian J. Pediatr."},{"key":"22426_CR10","doi-asserted-by":"publisher","first-page":"5535","DOI":"10.1113\/jp278523","volume":"597","author":"M Kasai","year":"2019","unstructured":"Kasai, M. et al. Early sinusoidal heart rate patterns and heart rate variability to assess hypoxia-ischaemia in near-term fetal sheep. J. Physiol. 597, 5535\u20135548. https:\/\/doi.org\/10.1113\/jp278523 (2019).","journal-title":"J. Physiol."},{"key":"22426_CR11","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1038\/jp.2014.108","volume":"34","author":"AN Massaro","year":"2014","unstructured":"Massaro, A. N. et al. Heart rate variability in encephalopathic newborns during and after therapeutic hypothermia. J. Perinatol. 34, 836\u2013841. https:\/\/doi.org\/10.1038\/jp.2014.108 (2014).","journal-title":"J. Perinatol."},{"key":"22426_CR12","doi-asserted-by":"publisher","first-page":"Cd003311","DOI":"10.1002\/14651858.CD003311.pub3","volume":"2013","author":"SE Jacobs","year":"2013","unstructured":"Jacobs, S. E. et al. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst. Rev. 2013, Cd003311. https:\/\/doi.org\/10.1002\/14651858.CD003311.pub3 (2013).","journal-title":"Cochrane Database Syst. Rev."},{"key":"22426_CR13","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1053\/j.semperi.2015.12.005","volume":"40","author":"RE Giesinger","year":"2016","unstructured":"Giesinger, R. E. & McNamara, P. J. Hemodynamic instability in the critically ill neonate: An approach to cardiovascular support based on disease pathophysiology. Semin Perinatol. 40, 174\u2013188. https:\/\/doi.org\/10.1053\/j.semperi.2015.12.005 (2016).","journal-title":"Semin Perinatol."},{"key":"22426_CR14","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1542\/peds.106.1.92","volume":"106","author":"M Thoresen","year":"2000","unstructured":"Thoresen, M. & Whitelaw, A. Cardiovascular changes during mild therapeutic hypothermia and rewarming in infants with hypoxic-ischemic encephalopathy. Pediatrics 106, 92\u201399. https:\/\/doi.org\/10.1542\/peds.106.1.92 (2000).","journal-title":"Pediatrics"},{"key":"22426_CR15","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1097\/pcc.0000000000001094","volume":"18","author":"AN Massaro","year":"2017","unstructured":"Massaro, A. N. et al. Effect of temperature on heart rate variability in neonatal ICU patients with hypoxic-ischemic encephalopathy. Pediatr. Crit. Care Med. 18, 349\u2013354. https:\/\/doi.org\/10.1097\/pcc.0000000000001094 (2017).","journal-title":"Pediatr. Crit. Care Med."},{"key":"22426_CR16","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/jp.2017.42","volume":"37","author":"ZA Vesoulis","year":"2017","unstructured":"Vesoulis, Z. A., Rao, R., Trivedi, S. B. & Mathur, A. M. The effect of therapeutic hypothermia on heart rate variability. J. Perinatol. 37, 679\u2013683. https:\/\/doi.org\/10.1038\/jp.2017.42 (2017).","journal-title":"J. Perinatol."},{"key":"22426_CR17","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1038\/pr.2016.245","volume":"81","author":"RM Goulding","year":"2017","unstructured":"Goulding, R. M. et al. Heart rate variability in hypoxic ischemic encephalopathy during therapeutic hypothermia. Pediatr. Res. 81, 609\u2013615. https:\/\/doi.org\/10.1038\/pr.2016.245 (2017).","journal-title":"Pediatr. Res."},{"key":"22426_CR18","doi-asserted-by":"publisher","DOI":"10.3791\/52454","author":"KJ Kyng","year":"2015","unstructured":"Kyng, K. J. et al. A piglet model of neonatal hypoxic-ischemic encephalopathy. J. Vis. Exp. https:\/\/doi.org\/10.3791\/52454 (2015).","journal-title":"J. Vis. Exp."},{"key":"22426_CR19","doi-asserted-by":"publisher","first-page":"299","DOI":"10.3389\/fped.2020.00299","volume":"8","author":"TCK Andelius","year":"2020","unstructured":"Andelius, T. C. K. et al. No added neuroprotective effect of remote ischemic postconditioning and therapeutic hypothermia after mild hypoxia-ischemia in a piglet model. Front. Pediatr. 8, 299. https:\/\/doi.org\/10.3389\/fped.2020.00299 (2020).","journal-title":"Front. Pediatr."},{"key":"22426_CR20","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1203\/00006450-199611000-00014","volume":"40","author":"M Thoresen","year":"1996","unstructured":"Thoresen, M. et al. A piglet survival model of posthypoxic encephalopathy. Pediatr. Res. 40, 738\u2013748. https:\/\/doi.org\/10.1203\/00006450-199611000-00014 (1996).","journal-title":"Pediatr. Res."},{"key":"22426_CR21","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1042\/cs0900097","volume":"90","author":"LA Fleisher","year":"1996","unstructured":"Fleisher, L. A. et al. Thermoregulation and heart rate variability. Clin. Sci. (London) 90, 97\u2013103. https:\/\/doi.org\/10.1042\/cs0900097 (1996).","journal-title":"Clin. Sci. (London)"},{"key":"22426_CR22","doi-asserted-by":"publisher","first-page":"e13287","DOI":"10.1111\/psyp.13287","volume":"56","author":"EJC de Geus","year":"2019","unstructured":"de Geus, E. J. C., Gianaros, P. J., Brindle, R. C., Jennings, J. R. & Berntson, G. G. Should heart rate variability be \u201ccorrected\u201d for heart rate? Biological, quantitative, and interpretive considerations. Psychophysiology 56, e13287. https:\/\/doi.org\/10.1111\/psyp.13287 (2019).","journal-title":"Psychophysiology"},{"key":"22426_CR23","doi-asserted-by":"publisher","first-page":"e0157557","DOI":"10.1371\/journal.pone.0157557","volume":"11","author":"SZ Kazmi","year":"2016","unstructured":"Kazmi, S. Z. et al. Inverse correlation between heart rate variability and heart rate demonstrated by linear and nonlinear analysis. PLoS ONE 11, e0157557. https:\/\/doi.org\/10.1371\/journal.pone.0157557 (2016).","journal-title":"PLoS ONE"},{"key":"22426_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s004330050128","volume":"199","author":"SF Langer","year":"1999","unstructured":"Langer, S. F., Lambertz, M., Langhorst, P. & Schmidt, H. D. Interbeat interval variability in isolated working rat hearts at various dynamic conditions and temperatures. Res. Exp. Med. (Berlin) 199, 1\u201319. https:\/\/doi.org\/10.1007\/s004330050128 (1999).","journal-title":"Res. Exp. Med. (Berlin)"},{"key":"22426_CR25","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/bf00421205","volume":"45","author":"J Werner","year":"1980","unstructured":"Werner, J. & Reents, T. A contribution to the topography of temperature regulation in man. Eur. J. Appl. Physiol. Occup. Physiol. 45, 87\u201394. https:\/\/doi.org\/10.1007\/bf00421205 (1980).","journal-title":"Eur. J. Appl. Physiol. Occup. Physiol."},{"key":"22426_CR26","doi-asserted-by":"publisher","first-page":"6093","DOI":"10.1113\/jp275434","volume":"596","author":"K Yamaguchi","year":"2018","unstructured":"Yamaguchi, K. et al. Evolving changes in fetal heart rate variability and brain injury after hypoxia-ischaemia in preterm fetal sheep. J. Physiol. 596, 6093\u20136104. https:\/\/doi.org\/10.1113\/jp275434 (2018).","journal-title":"J. Physiol."},{"key":"22426_CR27","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1139\/apnm-2018-0248","volume":"44","author":"GJ Hodges","year":"2019","unstructured":"Hodges, G. J., Ferguson, S. A. H. & Cheung, S. S. Cardiac autonomic function during hypothermia and its measurement repeatability. Appl. Physiol. Nutr. Metab. 44, 31\u201336. https:\/\/doi.org\/10.1139\/apnm-2018-0248 (2019).","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"22426_CR28","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jpeds.2017.12.071","volume":"196","author":"H Campbell","year":"2018","unstructured":"Campbell, H. et al. Autonomic dysfunction in neonates with hypoxic ischemic encephalopathy undergoing therapeutic hypothermia impairs physiological responses to routine care events. J. Pediatr. 196, 38\u201344. https:\/\/doi.org\/10.1016\/j.jpeds.2017.12.071 (2018).","journal-title":"J. Pediatr."},{"key":"22426_CR29","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1177\/026119299502300306","volume":"23","author":"WM Russell","year":"1995","unstructured":"Russell, W. M. The development of the three Rs concept. Altern. Lab. Anim. 23, 298\u2013304 (1995).","journal-title":"Altern. Lab. Anim."},{"key":"22426_CR30","doi-asserted-by":"publisher","first-page":"2246","DOI":"10.1177\/0271678x18791631","volume":"39","author":"JO Davidson","year":"2019","unstructured":"Davidson, J. O. et al. Limited benefit of slow rewarming after cerebral hypothermia for global cerebral ischemia in near-term fetal sheep. J. Cereb. Blood Flow Metab. 39, 2246\u20132257. https:\/\/doi.org\/10.1177\/0271678x18791631 (2019).","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"22426_CR31","doi-asserted-by":"publisher","first-page":"277","DOI":"10.2165\/11319360-000000000-00000","volume":"49","author":"MP van den Broek","year":"2010","unstructured":"van den Broek, M. P., Groenendaal, F., Egberts, A. C. & Rademaker, C. M. Effects of hypothermia on pharmacokinetics and pharmacodynamics: A systematic review of preclinical and clinical studies. Clin. Pharmacokinet. 49, 277\u2013294. https:\/\/doi.org\/10.2165\/11319360-000000000-00000 (2010).","journal-title":"Clin. Pharmacokinet."},{"key":"22426_CR32","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/s1053-0770(96)80138-8","volume":"10","author":"B Zickmann","year":"1996","unstructured":"Zickmann, B. et al. Changes in heart rate variability during induction of anesthesia with fentanyl and midazolam. J. Cardiothorac. Vasc. Anesth. 10, 609\u2013613. https:\/\/doi.org\/10.1016\/s1053-0770(96)80138-8 (1996).","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"22426_CR33","doi-asserted-by":"publisher","first-page":"3000410","DOI":"10.1371\/journal.pbio.3000410","volume":"18","author":"N du Percie Sert","year":"2020","unstructured":"du Percie Sert, N. et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol. 18, 3000410. https:\/\/doi.org\/10.1371\/journal.pbio.3000410 (2020).","journal-title":"PLoS Biol."},{"key":"22426_CR34","doi-asserted-by":"publisher","first-page":"10652","DOI":"10.1038\/s41598-019-47052-4","volume":"9","author":"TCK Andelius","year":"2019","unstructured":"Andelius, T. C. K. et al. Consequence of insertion trauma - effect on early measurements when using intracerebral devices. Sci. Rep. 9, 10652. https:\/\/doi.org\/10.1038\/s41598-019-47052-4 (2019).","journal-title":"Sci. Rep."},{"key":"22426_CR35","doi-asserted-by":"publisher","first-page":"e844","DOI":"10.1542\/peds.2007-1987","volume":"121","author":"A R\u00f3ka","year":"2008","unstructured":"R\u00f3ka, A. et al. Elevated morphine concentrations in neonates treated with morphine and prolonged hypothermia for hypoxic ischemic encephalopathy. Pediatrics 121, e844-849. https:\/\/doi.org\/10.1542\/peds.2007-1987 (2008).","journal-title":"Pediatrics"},{"key":"22426_CR36","doi-asserted-by":"publisher","unstructured":"Govindan, R. B. et al. Effect of EKG sampling rate on heart rate variability analysis. In 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 6780\u20136783. doi:https:\/\/doi.org\/10.1109\/embc.2019.8857754 (2019)","DOI":"10.1109\/embc.2019.8857754"},{"key":"22426_CR37","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.cmpb.2013.07.024","volume":"113","author":"MP Tarvainen","year":"2014","unstructured":"Tarvainen, M. P., Niskanen, J. P., Lipponen, J. A., Ranta-Aho, P. O. & Karjalainen, P. A. Kubios HRV\u2013heart rate variability analysis software. Comput. Methods Programs Biomed. 113, 210\u2013220. https:\/\/doi.org\/10.1016\/j.cmpb.2013.07.024 (2014).","journal-title":"Comput. Methods Programs Biomed."},{"key":"22426_CR38","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1088\/0967-3334\/30\/8\/009","volume":"30","author":"OM Doyle","year":"2009","unstructured":"Doyle, O. M. et al. Heart rate variability during sleep in healthy term newborns in the early postnatal period. Physiol. Meas. 30, 847\u2013860. https:\/\/doi.org\/10.1088\/0967-3334\/30\/8\/009 (2009).","journal-title":"Physiol. Meas."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-22426-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-22426-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-22426-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T18:14:48Z","timestamp":1667240088000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-22426-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,31]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["22426"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-22426-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,31]]},"assertion":[{"value":"12 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 October 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 October 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18282"}}