{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T01:17:41Z","timestamp":1788484661092,"version":"build-2803163510"},"reference-count":58,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T00:00:00Z","timestamp":1557446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>The electrical stability of the myocardium is dependent on the dynamic balance between sympathetic and parasympathetic influences on the heart, which is reflected by heart rate variability (HRV). Reduced HRV is a proposed predictor of sudden death caused by ventricular tachyarrhythmias in cardiac patients. However, the link between individual differences in HRV and ventricular tachyarrhythmic risk in populations without known pre-existing cardiac conditions is less well explored. In this study we investigated the extent to which individual differences in resting state HRV predict susceptibility to spontaneous and pharmacologically-induced ventricular arrhythmias in healthy rats. Radiotelemetric transmitters were implanted in 42 adult male Wild-type Groningen rats. ECG signals were recorded during 24-h resting conditions and under \u03b2-adrenoceptor pharmacological stimulation with isoproterenol and analyzed by means of time- and frequency-domain indexes of HRV. No significant association was found between individual differences in resting measures of HRV and spontaneous incidence of ventricular arrhythmias. However, lower resting values of HRV predicted a higher number of ventricular ectopic beats following \u03b2-adrenergic pharmacological stimulation with isoproterenol (0.02 mg\/kg). Moreover, after isoproterenol administration, one rat with low resting HRV developed sustained ventricular tachycardia that led to death. The present results might be indicative of the potential utility of HRV measures of resting cardiac autonomic function for the prediction of ventricular arrhythmias, particularly during conditions of strong sympathetic activation, in populations without known cardiac disease.<\/jats:p>","DOI":"10.3390\/jcm8050655","type":"journal-article","created":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T03:57:07Z","timestamp":1557719827000},"page":"655","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Resting Heart Rate Variability Predicts Vulnerability to Pharmacologically-Induced Ventricular Arrhythmias in Male Rats"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9053-7976","authenticated-orcid":false,"given":"Luca","family":"Carnevali","sequence":"first","affiliation":[{"name":"Stress Physiology Lab, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43121 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Statello","sequence":"additional","affiliation":[{"name":"Stress Physiology Lab, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43121 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Sgoifo","sequence":"additional","affiliation":[{"name":"Stress Physiology Lab, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43121 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.neubiorev.2011.11.009","article-title":"A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and health","volume":"36","author":"Thayer","year":"2012","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/S0022-3476(97)70280-4","article-title":"Effect of physical training on heart-period variability in obese children","volume":"130","author":"Gutin","year":"1997","journal-title":"J. Pediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1161\/01.HYP.35.4.880","article-title":"Effects of work stress on ambulatory blood pressure, heart rate, and heart rate variability","volume":"35","author":"Vrijkotte","year":"2000","journal-title":"Hypertension"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1179\/1476830515Y.0000000018","article-title":"Short-term effects of espresso coffee on heart rate variability and blood pressure in habitual and non-habitual coffee consumers\u2014A randomized crossover study","volume":"19","author":"Thayer","year":"2016","journal-title":"Nutr. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1111\/j.1542-474X.2005.00636.x","article-title":"Cigarette smoking and heart rate variability: Dynamic influence of parasympathetic and sympathetic maneuvers","volume":"10","author":"Barutcu","year":"2005","journal-title":"Ann. Noninvasive Electrocardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ijpsycho.2016.04.008","article-title":"Genetic influences on heart rate variability","volume":"115","author":"Golosheykin","year":"2017","journal-title":"Int. J. Psychophysiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1111\/j.1469-8986.2009.00793.x","article-title":"Genetic influences on heart rate variability at rest and during stress","volume":"46","author":"Wang","year":"2009","journal-title":"Psychophysiology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1161\/01.CIR.103.16.2072","article-title":"Baroreflex sensitivity and heart rate variability in the identification of patients at risk for life-threatening arrhythmias: Implications for clinical trials","volume":"103","author":"Pinna","year":"2001","journal-title":"Circulation"},{"key":"ref_9","first-page":"F72","article-title":"The autonomic nervous system and sudden death","volume":"19","author":"Schwartz","year":"1998","journal-title":"Eur. Heart J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ijcard.2009.09.543","article-title":"The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors","volume":"141","author":"Thayer","year":"2010","journal-title":"Int. J. Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.ijcard.2010.02.048","article-title":"Ignoring lack of association of heart rate variability with cardiovascular disease and risk factors: Response to the manuscript \u201cThe relationship of autonomic imbalance, heart rate variability cardiovascular disease risk factors\u201d by Julian F. Thayer, Shelby S. Yamamoto, Jos F. Brosschot","volume":"145","author":"Kluttig","year":"2010","journal-title":"Int. J. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1136\/hrt.2003.026146","article-title":"Autonomic changes in patients with heart failure and in post-myocardial infarction patients","volume":"90","author":"Frenneaux","year":"2004","journal-title":"Heart"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3389\/fphys.2012.00041","article-title":"Clinical application of heart rate variability after acute myocardial infarction","volume":"3","author":"Huikuri","year":"2012","journal-title":"Front. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1161\/01.CIR.0000047275.25795.17","article-title":"Short-term heart rate variability strongly predicts sudden cardiac death in chronic heart failure patients","volume":"107","author":"Pinna","year":"2003","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1159\/000177071","article-title":"Reduced beat-to-beat changes of heart rate: An important risk factor after acute myocardial infarction","volume":"87","author":"Reinhardt","year":"1996","journal-title":"Cardiology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1111\/j.1540-8159.2006.00457.x","article-title":"The role of heart rate variability in prognosis for different modes of death in chronic heart failure","volume":"29","author":"Sandercock","year":"2006","journal-title":"Pacing Clin. Electrophysiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1093\/oxfordjournals.aje.a009959","article-title":"Both decreased and increased heart rate variability on the standard 10-second electrocardiogram predict cardiac mortality in the elderly: The Rotterdam study","volume":"150","author":"Kors","year":"1999","journal-title":"Am. J. Epidemiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1093\/oxfordjournals.aje.a009049","article-title":"Heart rate variability from short electrocardiographic recordings predicts mortality from all causes in middle-aged and elderly men. The Zutphen study","volume":"145","author":"Dekker","year":"1997","journal-title":"Am. J. Epidemiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.yjmcc.2018.02.001","article-title":"Autonomic conflict exacerbates long QT associated ventricular arrhythmias","volume":"116","author":"Winter","year":"2018","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"289","DOI":"10.4065\/84.3.289","article-title":"Ventricular tachycardia and sudden cardiac death","volume":"84","author":"Koplan","year":"2009","journal-title":"Mayo Clin. Proc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/0002-9149(88)91295-7","article-title":"Mechanism of death and prevalence of myocardial ischemic symptoms in the terminal event after acute myocardial infarction","volume":"61","author":"Marcus","year":"1988","journal-title":"Am. J. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.autneu.2016.07.001","article-title":"Neuro-cardiac interaction in malignant ventricular arrhythmia and sudden cardiac death","volume":"199","author":"Ng","year":"2016","journal-title":"Auton. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1093\/europace\/eus341","article-title":"Heart rate variability and first cardiovascular event in populations without known cardiovascular disease: Meta-analysis and dose-response meta-regression","volume":"15","author":"Hillebrand","year":"2013","journal-title":"Europace"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"118","DOI":"10.3389\/fphys.2014.00118","article-title":"Vagal modulation of resting heart rate in rats: The role of stress, psychosocial factors, and physical exercise","volume":"5","author":"Carnevali","year":"2014","journal-title":"Front. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.neubiorev.2013.12.005","article-title":"The socially stressed heart. Insights from studies in rodents","volume":"39","author":"Sgoifo","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_26","unstructured":"Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology (1996). Heart rate variability: Standards of measurement, physiological interpretation and clinical use. Circulation, 93, 1043\u20131065."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"213","DOI":"10.3389\/fpsyg.2017.00213","article-title":"Heart rate variability and cardiac vagal tone in psychophysiological research\u2014Recommendations for experiment planning, data analysis, and data reporting","volume":"8","author":"Laborde","year":"2017","journal-title":"Front. Psychol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1161\/01.CIR.84.2.482","article-title":"Cardiovascular neural regulation explored in the frequency domain","volume":"84","author":"Malliani","year":"1991","journal-title":"Circulation"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/psyp.12027","article-title":"The utility of low frequency heart rate variability as an index of sympathetic cardiac tone: A review with emphasis on a reanalysis of previous studies","volume":"50","author":"Langewitz","year":"2013","journal-title":"Psychophysiology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1113\/expphysiol.2010.056259","article-title":"Low-frequency power of heart rate variability is not a measure of cardiac sympathetic tone but may be a measure of modulation of cardiac autonomic outflows by baroreflexes","volume":"96","author":"Goldstein","year":"2011","journal-title":"Exp. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/j.1469-8986.1997.tb02140.x","article-title":"Heart rate variability: Origins, methods, and interpretive caveats","volume":"34","author":"Berntson","year":"1997","journal-title":"Psychophysiology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3389\/fphys.2013.00026","article-title":"The LF\/HF ratio does not accurately measure cardiac sympatho-vagal balance","volume":"4","author":"Billman","year":"2013","journal-title":"Front. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1111\/j.1469-8986.2008.00710.x","article-title":"Comparing low frequency heart rate variability and preejection period: Two sides of a different coin","volume":"45","author":"Goedhart","year":"2008","journal-title":"Psychophysiology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1161\/CIRCRESAHA.113.302549","article-title":"Role of the autonomic nervous system in modulating cardiac arrhythmias","volume":"114","author":"Shen","year":"2014","journal-title":"Circ. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.physbeh.2012.01.022","article-title":"Social defeat and isolation induce clear signs of a depression-like state, but modest cardiac alterations in wild-type rats","volume":"106","author":"Carnevali","year":"2012","journal-title":"Physiol. Behav."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/S0031-9384(96)00228-4","article-title":"Electrode positioning for reliable telemetry ECG recordings during social stress in unrestrained rats","volume":"60","author":"Sgoifo","year":"1996","journal-title":"Physiol. Behav."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"18218","DOI":"10.1038\/srep18218","article-title":"Cardioprotective effects of fatty acid amide hydrolase inhibitor URB694, in a rodent model of trait anxiety","volume":"5","author":"Carnevali","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.pharmthera.2013.04.008","article-title":"The lambeth conventions (II): Guidelines for the study of animal and human ventricular and supraventricular arrhythmias","volume":"139","author":"Curtis","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/0008-6363(96)00086-7","article-title":"Short- and long-term reproducibility of time and frequency domain heart rate variability measurements in normal subjects","volume":"32","author":"Pitzalis","year":"1996","journal-title":"Cardiovasc. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ijpsycho.2012.01.011","article-title":"Test-retest reliability of regional electroencephalogram (EEG) and cardiovascular measures in social anxiety disorder (SAD)","volume":"84","author":"Schmidt","year":"2012","journal-title":"Int. J. Psychophysiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.archger.2015.11.011","article-title":"Aging, heart rate variability and patterns of autonomic regulation of the heart","volume":"63","author":"Oliveira","year":"2016","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_42","first-page":"3178","article-title":"Attenuation of vagal modulation with aging: Univariate and bivariate analysis of HRV","volume":"2017","author":"Junior","year":"2017","journal-title":"Conf. Proc. IEEE Eng. Med. Biol. Soc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1093\/europace\/eul063","article-title":"Heart rate variability in an ageing population and its association with lifestyle and cardiovascular risk factors: Results of the SAPALDIA study","volume":"8","author":"Schindler","year":"2006","journal-title":"Europace"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1177\/2047487317736827","article-title":"Sudden death: Neurogenic causes, prediction and prevention","volume":"25","author":"Sarenac","year":"2018","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Rossi, S., Fortunati, I., Carnevali, L., Baruffi, S., Mastorci, F., Trombini, M., Sgoifo, A., Corradi, D., Callegari, S., and Miragoli, M. (2014). The effect of aging on the specialized conducting system: A telemetry ECG study in rats over a 6 month period. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112697"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ijcard.2018.08.005","article-title":"Heart rate variability as a marker of healthy ageing","volume":"275","author":"Tan","year":"2019","journal-title":"Int. J. Cardiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.jelectrocard.2008.02.014","article-title":"Time domain parameters can be estimated with less statistical error than frequency domain parameters in the analysis of heart rate variability","volume":"41","author":"Kuss","year":"2008","journal-title":"J. Electrocardiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1056\/NEJM198501243120401","article-title":"Long-term follow-up of asymptomatic healthy subjects with frequent and complex ventricular ectopy","volume":"312","author":"Kennedy","year":"1985","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1046\/j.1460-9592.2001.00166.x","article-title":"Reversal of tachycardia induced cardiomyopathy following ablation of repetitive monomorphic right ventricular outflow tract tachycardia","volume":"24","author":"Grimm","year":"2001","journal-title":"Pacing Clin. Electrophysiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1136\/hrt.2008.159558","article-title":"Prognostic significance of frequent premature ventricular contractions originating from the ventricular outflow tract in patients with normal left ventricular function","volume":"95","author":"Niwano","year":"2009","journal-title":"Heart"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Carnevali, L., Trombini, M., Porta, A., Montano, N., de Boer, S.F., and Sgoifo, A. (2013). Vagal withdrawal and susceptibility to cardiac arrhythmias in rats with high trait aggressiveness. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068316"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e72","DOI":"10.1161\/01.RES.0000264101.06417.33","article-title":"Autonomic nerve stimulation reverses ventricular repolarization sequence in rabbit hearts","volume":"100","author":"Mantravadi","year":"2007","journal-title":"Circ. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.hrthm.2009.01.035","article-title":"Sympathetic nerve stimulation produces spatial heterogeneities of action potential restitution","volume":"6","author":"Ng","year":"2009","journal-title":"Heart Rhythm"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.hrthm.2013.11.028","article-title":"Cardiac sympathetic denervation in patients with refractory ventricular arrhythmias or electrical storm: Intermediate and long-term follow-up","volume":"11","author":"Vaseghi","year":"2014","journal-title":"Heart Rhythm"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1097\/PSY.0b013e318276cb0d","article-title":"Structural and electrical myocardial remodeling in a rodent model of depression","volume":"75","author":"Carnevali","year":"2013","journal-title":"Psychosom. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.autneu.2016.08.016","article-title":"Cardiac sympatho-vagal balance and ventricular arrhythmia","volume":"199","author":"Kalla","year":"2016","journal-title":"Auton. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4073","DOI":"10.1113\/jphysiol.2013.257758","article-title":"Myths and realities of the cardiac vagus","volume":"591","author":"Coote","year":"2013","journal-title":"J. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1111\/j.1469-7793.2001.00547.x","article-title":"Vagus nerve stimulation decreases left ventricular contractility in vivo in the human and pig heart","volume":"534","author":"Lewis","year":"2001","journal-title":"J. Physiol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/8\/5\/655\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:51:00Z","timestamp":1760187060000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/8\/5\/655"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,10]]},"references-count":58,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["jcm8050655"],"URL":"https:\/\/doi.org\/10.3390\/jcm8050655","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,10]]}}}