Analyze Diet
PloS one2018; 13(3); e0194008; doi: 10.1371/journal.pone.0194008

Cardiac electrophysiological adaptations in the equine athlete-Restitution analysis of electrocardiographic features.

Abstract: Exercising horses uniquely accommodate 7-8-fold increases in heart rate (HR). The present experiments for the first time analysed the related adaptations in action potential (AP) restitution properties recorded by in vivo telemetric electrocardiography from Thoroughbred horses. The horses were subjected to a period of acceleration from walk to canter. The QRS durations, and QT and TQ intervals yielded AP conduction velocities, AP durations (APDs) and diastolic intervals respectively. From these, indices of active, λ = QT/(QRS duration), and resting, λ0 = TQ/(QRS duration), AP wavelengths were calculated. Critical values of QT and TQ intervals, and of λ and λ0 at which plots of these respective pairs of functions showed unity slope, were obtained. These were reduced by 38.9±2.7% and 86.2±1.8%, and 34.1±3.3% and 85.9±1.2%, relative to their resting values respectively. The changes in λ were attributable to falls in QT interval rather than QRS duration. These findings both suggested large differences between the corresponding critical (129.1±10.8 or 117.4±5.6 bpm respectively) and baseline HRs (32.9±2.1 (n = 7) bpm). These restitution analyses thus separately identified concordant parameters whose adaptations ensure the wide range of HRs over which electrophysiological activation takes place in an absence of heart block or arrhythmias in equine hearts. Since the horse is amenable to this in vivo electrophysiological analysis and displays a unique wide range of heart rates, it could be a novel cardiac electrophysiology animal model for the study of sudden cardiac death in human athletes.
Publication Date: 2018-03-09 PubMed ID: 29522557PubMed Central: PMC5844547DOI: 10.1371/journal.pone.0194008Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study explores how horses adapt their heart rate during exercise, demonstrating electrophysiological changes which enable a broad range of heart rates. The research can potentially advance our understanding of sudden cardiac death in human athletes, with horses serving as a feasible experimental model due to their unique electrophysiological characteristics.

Research context and objectives

  • While it is known that exercising horses can accommodate significant increases in heart rate, the electrophysiological adaptations associated with this are less understood.
  • The purpose of this study is to investigate these physiological changes through analysis of the horses’ action potential or AP (the short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls).

Research Methodology

  • The study used in vivo telemetric electrocardiography (ECG) to record data from Thoroughbred horses subjected to exercise conditions, transitioning from a walk to a canter.
  • Various ECG features were measured, including the durations of the QRS complex, QT interval (time between start of the Q wave and the end of the T wave in the heart’s electrical cycle), and TQ interval (time from end of the T wave to the start of the next QRS complex), providing insights into AP conduction velocities, AP durations (APDs), and diastolic intervals.
  • From these measurements, the researchers calculated indices of active and resting AP wavelengths, respectively labeled λ and λ0. The critical values at which these functions showed unity slope were also obtained.

Findings

  • The study found that these critical values reduced by significant percentages relative to their resting values. The changes in λ were due to decreases in QT interval rather than changes in QRS duration.
  • They observed large differences between baseline heart rates and the critical values, indicative of the electrophysiological adaptations that allow a wide range of heart rates without inducing heart block or arrhythmias.

Implications

  • The results provide insights into adaptive mechanisms in the equine heart that allow for enhanced heart rate performance during exercise.
  • Given the unique range of heart rates exhibited by horses, they could serve as an appropriate animal model for studying cardiac electrophysiology, potentially aiding our understanding of sudden cardiac deaths in human athletes.

Cite This Article

APA
Li M, Chadda KR, Matthews GDK, Marr CM, Huang CL, Jeevaratnam K. (2018). Cardiac electrophysiological adaptations in the equine athlete-Restitution analysis of electrocardiographic features. PLoS One, 13(3), e0194008. https://doi.org/10.1371/journal.pone.0194008

Publication

ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 13
Issue: 3
Pages: e0194008
PII: e0194008

Researcher Affiliations

Li, Mengye
  • Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom.
Chadda, Karan R
  • Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom.
  • Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.
Matthews, Gareth D K
  • Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom.
Marr, Celia M
  • Rossdales Equine Hospital and Diagnostic Centre, Exning, Suffolk, United Kingdom.
Huang, Christopher L-H
  • Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom.
  • Division of Cardiovascular Biology, Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
Jeevaratnam, Kamalan
  • Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom.
  • Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.

MeSH Terms

  • Action Potentials
  • Adaptation, Physiological
  • Animals
  • Electrocardiography / veterinary
  • Female
  • Heart Conduction System / physiology
  • Horses / physiology
  • Male
  • Physical Conditioning, Animal / physiology
  • Running / physiology
  • Telemetry / veterinary
  • Walking / physiology

Grant Funding

  • Wellcome Trust
  • MR/M001288/1 / Medical Research Council
  • PG/14/79/31102 / British Heart Foundation

Conflict of Interest Statement

The authors have declared that no competing interests exist.

References

This article includes 52 references
  1. De Backer G, Ambrosioni E, Borch-Johnsen K, Brotons C, Cifkova R, Dallongeville J, Ebrahim S, Faergeman O, Graham I, Mancia G, Manger Cats V, Orth-Gomér K, Perk J, Pyörälä K, Rodicio JL, Sans S, Sansoy V, Sechtem U, Silber S, Thomsen T, Wood D. European guidelines on cardiovascular disease prevention in clinical practice. Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice.. Eur Heart J 2003 Sep;24(17):1601-10.
    pubmed: 12964575doi: 10.1016/s0195-668x(03)00347-6google scholar: lookup
  2. Wasfy MM, Hutter AM, Weiner RB. Sudden Cardiac Death in Athletes.. Methodist Debakey Cardiovasc J 2016 Apr-Jun;12(2):76-80.
    doi: 10.14797/mdcj-12-2-76pmc: PMC4969030pubmed: 27486488google scholar: lookup
  3. Chandra N, Bastiaenen R, Papadakis M, Sharma S. Sudden cardiac death in young athletes: practical challenges and diagnostic dilemmas.. J Am Coll Cardiol 2013 Mar 12;61(10):1027-40.
    doi: 10.1016/j.jacc.2012.08.1032pubmed: 23473408google scholar: lookup
  4. Corrado D, Basso C, Pavei A, Michieli P, Schiavon M, Thiene G. Trends in sudden cardiovascular death in young competitive athletes after implementation of a preparticipation screening program.. JAMA 2006 Oct 4;296(13):1593-601.
    doi: 10.1001/jama.296.13.1593pubmed: 17018804google scholar: lookup
  5. Drezner JA, Rao AL, Heistand J, Bloomingdale MK, Harmon KG. Effectiveness of emergency response planning for sudden cardiac arrest in United States high schools with automated external defibrillators.. Circulation 2009 Aug 11;120(6):518-25.
  6. Harmon KG, Asif IM, Klossner D, Drezner JA. Incidence of sudden cardiac death in National Collegiate Athletic Association athletes.. Circulation 2011 Apr 19;123(15):1594-600.
  7. Baldesberger S, Bauersfeld U, Candinas R, Seifert B, Zuber M, Ritter M, Jenni R, Oechslin E, Luthi P, Scharf C, Marti B, Attenhofer Jost CH. Sinus node disease and arrhythmias in the long-term follow-up of former professional cyclists.. Eur Heart J 2008 Jan;29(1):71-8.
    doi: 10.1093/eurheartj/ehm555pubmed: 18065754google scholar: lookup
  8. D'Souza A, Sharma S, Boyett MR. CrossTalk opposing view: bradycardia in the trained athlete is attributable to a downregulation of a pacemaker channel in the sinus node.. J Physiol 2015 Apr 15;593(8):1749-51.
  9. Hood S, Northcote RJ. Cardiac assessment of veteran endurance athletes: a 12 year follow up study.. Br J Sports Med 1999 Aug;33(4):239-43.
    pmc: PMC1756191pubmed: 10450477doi: 10.1136/bjsm.33.4.239google scholar: lookup
  10. D'Souza A, Bucchi A, Johnsen AB, Logantha SJ, Monfredi O, Yanni J, Prehar S, Hart G, Cartwright E, Wisloff U, Dobryznski H, DiFrancesco D, Morris GM, Boyett MR. Exercise training reduces resting heart rate via downregulation of the funny channel HCN4.. Nat Commun 2014 May 13;5:3775.
    doi: 10.1038/ncomms4775pmc: PMC4024745pubmed: 24825544google scholar: lookup
  11. Aschar-Sobbi R, Izaddoustdar F, Korogyi AS, Wang Q, Farman GP, Yang F, Yang W, Dorian D, Simpson JA, Tuomi JM, Jones DL, Nanthakumar K, Cox B, Wehrens XH, Dorian P, Backx PH. Increased atrial arrhythmia susceptibility induced by intense endurance exercise in mice requires TNFα.. Nat Commun 2015 Jan 19;6:6018.
    doi: 10.1038/ncomms7018pmc: PMC4661059pubmed: 25598495google scholar: lookup
  12. Benito B, Gay-Jordi G, Serrano-Mollar A, Guasch E, Shi Y, Tardif JC, Brugada J, Nattel S, Mont L. Cardiac arrhythmogenic remodeling in a rat model of long-term intensive exercise training.. Circulation 2011 Jan 4;123(1):13-22.
  13. Janssen PM, Biesiadecki BJ, Ziolo MT, Davis JP. The Need for Speed: Mice, Men, and Myocardial Kinetic Reserve.. Circ Res 2016 Jul 22;119(3):418-21.
  14. Buhl R, Petersen EE, Lindholm M, Bak L, Nostell K. Cardiac Arrhythmias in Standardbreds During and After Racing—Possible Association Between Heart Size, Valvular Regurgitations, and Arrhythmias. Journal of Equine Veterinary Science 2013;33(8):590–6.
  15. Finley MR, Li Y, Hua F, Lillich J, Mitchell KE, Ganta S, Gilmour RF Jr, Freeman LC. Expression and coassociation of ERG1, KCNQ1, and KCNE1 potassium channel proteins in horse heart.. Am J Physiol Heart Circ Physiol 2002 Jul;283(1):H126-38.
    doi: 10.1152/ajpheart.00622.2001pubmed: 12063283google scholar: lookup
  16. Sabir IN, Killeen MJ, Grace AA, Huang CL. Ventricular arrhythmogenesis: insights from murine models.. Prog Biophys Mol Biol 2008 Oct-Nov;98(2-3):208-18.
  17. Lyle CH, Uzal FA, McGorum BC, Aida H, Blissitt KJ, Case JT, Charles JT, Gardner I, Horadagoda N, Kusano K, Lam K, Pack JD, Parkin TD, Slocombe RF, Stewart BD, Boden LA. Sudden death in racing Thoroughbred horses: an international multicentre study of post mortem findings.. Equine Vet J 2011 May;43(3):324-31.
  18. Ryan N, Marr CM, McGladdery AJ. Survey of cardiac arrhythmias during submaximal and maximal exercise in Thoroughbred racehorses.. Equine Vet J 2005 May;37(3):265-8.
    pubmed: 15892238doi: 10.2746/0425164054530713google scholar: lookup
  19. Martin BB Jr, Reef VB, Parente EJ, Sage AD. Causes of poor performance of horses during training, racing, or showing: 348 cases (1992-1996).. J Am Vet Med Assoc 2000 Feb 15;216(4):554-8.
    pubmed: 10687012doi: 10.2460/javma.2000.216.554google scholar: lookup
  20. Williams RB, Harkins LS, Hammond CJ, Wood JL. Racehorse injuries, clinical problems and fatalities recorded on British racecourses from flat racing and National Hunt racing during 1996, 1997 and 1998.. Equine Vet J 2001 Sep;33(5):478-86.
    pubmed: 11558743doi: 10.2746/042516401776254808google scholar: lookup
  21. Birettoni F, Porciello F, Rishniw M, della Rocca G, Di Salvo A, Sgorbini M. Treatment of chronic atrial fibrillation in the horse with flecainide: personal observation.. Vet Res Commun 2007 Aug;31 Suppl 1:273-5.
    doi: 10.1007/s11259-007-0045-0pubmed: 17682893google scholar: lookup
  22. De Clercq D, van Loon G, Tavernier R, Duchateau L, Deprez P. Atrial and ventricular electrical and contractile remodeling and reverse remodeling owing to short-term pacing-induced atrial fibrillation in horses.. J Vet Intern Med 2008 Nov-Dec;22(6):1353-9.
  23. Haugaard MM, Pehrson S, Carstensen H, Flethøj M, Hesselkilde EZ, Praestegaard KF, Diness JG, Grunnet M, Jespersen T, Buhl R. Antiarrhythmic and electrophysiologic effects of flecainide on acutely induced atrial fibrillation in healthy horses.. J Vet Intern Med 2015 Jan;29(1):339-47.
    doi: 10.1111/jvim.12496pmc: PMC4858114pubmed: 25328012google scholar: lookup
  24. Ohmura H, Nukada T, Mizuno Y, Yamaya Y, Nakayama T, Amada A. Safe and efficacious dosage of flecainide acetate for treating equine atrial fibrillation.. J Vet Med Sci 2000 Jul;62(7):711-5.
    pubmed: 10945288doi: 10.1292/jvms.62.711google scholar: lookup
  25. van Loon G, Blissitt KJ, Keen JA, Young LE. Use of intravenous flecainide in horses with naturally-occurring atrial fibrillation.. Equine Vet J 2004 Nov;36(7):609-14.
    pubmed: 15581326doi: 10.2746/0425164044864516google scholar: lookup
  26. Matthews GD, Guzadhur L, Grace A, Huang CL. Nonlinearity between action potential alternans and restitution, which both predict ventricular arrhythmic properties in Scn5a+/- and wild-type murine hearts.. J Appl Physiol (1985) 2012 Jun;112(11):1847-63.
  27. Matthews GD, Guzadhur L, Sabir IN, Grace AA, Huang CL. Action potential wavelength restitution predicts alternans and arrhythmia in murine Scn5a(+/-) hearts.. J Physiol 2013 Sep 1;591(17):4167-88.
  28. Sabir IN, Li LM, Grace AA, Huang CL. Restitution analysis of alternans and its relationship to arrhythmogenicity in hypokalaemic Langendorff-perfused murine hearts.. Pflugers Arch 2008 Jan;455(4):653-66.
    doi: 10.1007/s00424-007-0327-ypmc: PMC2082653pubmed: 17704939google scholar: lookup
  29. Sabir IN, Li LM, Jones VJ, Goddard CA, Grace AA, Huang CL. Criteria for arrhythmogenicity in genetically-modified Langendorff-perfused murine hearts modelling the congenital long QT syndrome type 3 and the Brugada syndrome.. Pflugers Arch 2008 Jan;455(4):637-51.
    doi: 10.1007/s00424-007-0326-zpmc: PMC2082651pubmed: 17805561google scholar: lookup
  30. Pastore JM, Laurita KR, Rosenbaum DS. Importance of spatiotemporal heterogeneity of cellular restitution in mechanism of arrhythmogenic discordant alternans.. Heart Rhythm 2006 Jun;3(6):711-9.
    doi: 10.1016/j.hrthm.2006.02.1034pubmed: 16731476google scholar: lookup
  31. Padrini R, Speranza G, Nollo G, Bova S, Piovan D, Antolini R, Ferrari M. Adaptation of the QT interval to heart rate changes in isolated perfused guinea pig heart: influence of amiodarone and D-sotalol.. Pharmacol Res 1997 May;35(5):409-16.
    doi: 10.1006/phrs.1997.0152pubmed: 9299203google scholar: lookup
  32. Banville I, Chattipakorn N, Gray RA. Restitution dynamics during pacing and arrhythmias in isolated pig hearts.. J Cardiovasc Electrophysiol 2004 Apr;15(4):455-63.
  33. Nolasco JB, Dahlen RW. A graphic method for the study of alternation in cardiac action potentials.. J Appl Physiol 1968 Aug;25(2):191-6.
    doi: 10.1152/jappl.1968.25.2.191pubmed: 5666097google scholar: lookup
  34. Tolkacheva EG ZX. Nonlinear dynamics of periodically paced cardiac tissue. Nonlinear Dynamics 2012;68(3):347–63.
    doi: 10.1007/s11071-011-0241-xgoogle scholar: lookup
  35. Qu Z, Weiss JN. Dynamics and cardiac arrhythmias.. J Cardiovasc Electrophysiol 2006 Sep;17(9):1042-9.
  36. Noble D. The initiation of the heart beat.. Adv Sci 1966 Dec;23(114):412-8.
    pubmed: 5974438
  37. Wolff L. Electrocardiography. Philadelphia,: Saunders; 1950. viii, 187 p. p..
  38. Huang CL. From channels to systems: Ca(2+) -sensitive K(+) currents, alternans and cardiac arrhythmia.. J Physiol 2017 Apr 1;595(7):2299-2300.
    doi: 10.1113/JP273815pmc: PMC5374108pubmed: 28028806google scholar: lookup
  39. Broux B, De Clercq D, Decloedt A, Van Der Vekens N, Verheyen T, Ven S, Pardon B, van Loon G. Atrial Premature Depolarization-Induced Changes in QRS and T Wave Morphology on Resting Electrocardiograms in Horses.. J Vet Intern Med 2016 Jul;30(4):1253-9.
    doi: 10.1111/jvim.13957pmc: PMC5089572pubmed: 27209267google scholar: lookup
  40. Pedersen PJ, Karlsson M, Flethøj M, Trachsel DS, Kanters JK, Klaerke DA, Buhl R. Differences in the electrocardiographic QT interval of various breeds of athletic horses during rest and exercise.. J Vet Cardiol 2016 Sep;18(3):255-264.
    doi: 10.1016/j.jvc.2016.02.002pubmed: 27068842google scholar: lookup
  41. Rosenbaum DS, Albrecht P, Cohen RJ. Predicting sudden cardiac death from T wave alternans of the surface electrocardiogram: promise and pitfalls.. J Cardiovasc Electrophysiol 1996 Nov;7(11):1095-111.
  42. Rosenbaum DS, Jackson LE, Smith JM, Garan H, Ruskin JN, Cohen RJ. Electrical alternans and vulnerability to ventricular arrhythmias.. N Engl J Med 1994 Jan 27;330(4):235-41.
    doi: 10.1056/NEJM199401273300402pubmed: 8272084google scholar: lookup
  43. Salerno JA, Previtali M, Panciroli C, Klersy C, Chimienti M, Regazzi Bonora M, Marangoni E, Falcone C, Guasti L, Campana C. Ventricular arrhythmias during acute myocardial ischaemia in man. The role and significance of R-ST-T alternans and the prevention of ischaemic sudden death by medical treatment.. Eur Heart J 1986 May;7 Suppl A:63-75.
    pubmed: 3720777
  44. Platt SB, Vijgen JM, Albrecht P, Van Hare GF, Carlson MD, Rosenbaum DS. Occult T wave alternans in long QT syndrome.. J Cardiovasc Electrophysiol 1996 Feb;7(2):144-8.
  45. Gaeta SA, Christini DJ. Non-linear dynamics of cardiac alternans: subcellular to tissue-level mechanisms of arrhythmia.. Front Physiol 2012;3:157.
    doi: 10.3389/fphys.2012.00157pmc: PMC3389489pubmed: 22783195google scholar: lookup
  46. Weiss JN, Karma A, Shiferaw Y, Chen PS, Garfinkel A, Qu Z. From pulsus to pulseless: the saga of cardiac alternans.. Circ Res 2006 May 26;98(10):1244-53.
  47. Sabir IN, Ma N, Jones VJ, Goddard CA, Zhang Y, Kalin A, Grace AA, Huang CL. Alternans in genetically modified langendorff-perfused murine hearts modeling catecholaminergic polymorphic ventricular tachycardia.. Front Physiol 2010;1:126.
    doi: 10.3389/fphys.2010.00126pmc: PMC3059940pubmed: 21423368google scholar: lookup
  48. Noble D. The initiation of the heartbeat. 2d ed: Oxford University Press; 1979. xiii, 186 p. p..
  49. Fossa AA, Zhou M, Robinson A, Purkayastha J, Martin P. Use of ECG restitution (beat-to-beat QT-TQ interval analysis) to assess arrhythmogenic risk of QTc prolongation with guanfacine.. Ann Noninvasive Electrocardiol 2014 Nov;19(6):582-94.
    doi: 10.1111/anec.12202pmc: PMC6931917pubmed: 25200912google scholar: lookup
  50. Kijtawornrat A, Panyasing Y, Del Rio C, Hamlin RL. Assessment of ECG interval and restitution parameters in the canine model of short QT syndrome.. J Pharmacol Toxicol Methods 2010 May-Jun;61(3):231-7.
    doi: 10.1016/j.vascn.2010.02.001pubmed: 20156577google scholar: lookup
  51. Fossa AA, Wisialowski T, Crimin K. QT prolongation modifies dynamic restitution and hysteresis of the beat-to-beat QT-TQ interval relationship during normal sinus rhythm under varying states of repolarization.. J Pharmacol Exp Ther 2006 Feb;316(2):498-506.
    doi: 10.1124/jpet.105.095471pubmed: 16204470google scholar: lookup
  52. Hothi SS, Booth SW, Sabir IN, Killeen MJ, Simpson F, Zhang Y, Grace AA, Huang CL. Arrhythmogenic substrate and its modification by nicorandil in a murine model of long QT type 3 syndrome.. Prog Biophys Mol Biol 2008 Oct-Nov;98(2-3):267-80.

Citations

This article has been cited 7 times.
  1. Premont A, Saadeh K, Edling C, Lewis R, Marr CM, Jeevaratnam K. Cardiac ion channel expression in the equine model - In-silico prediction utilising RNA sequencing data from mixed tissue samples. Physiol Rep 2022 Jul;10(14):e15273.
    doi: 10.14814/phy2.15273pubmed: 35880716google scholar: lookup
  2. Huang YH, Alexeenko V, Tse G, Huang CL, Marr CM, Jeevaratnam K. ECG Restitution Analysis and Machine Learning to Detect Paroxysmal Atrial Fibrillation: Insight from the Equine Athlete as a Model for Human Athletes. Function (Oxf) 2021;2(1):zqaa031.
    doi: 10.1093/function/zqaa031pubmed: 35330977google scholar: lookup
  3. Alexeenko V, Fraser JA, Dolgoborodov A, Bowen M, Huang CL, Marr CM, Jeevaratnam K. The application of Lempel-Ziv and Titchener complexity analysis for equine telemetric electrocardiographic recordings. Sci Rep 2019 Feb 22;9(1):2619.
    doi: 10.1038/s41598-019-38935-7pubmed: 30796330google scholar: lookup
  4. Avison A, Goderre BG, Pyle WG, Physick-Sheard PW. QT Interval and Cardiac Restitution Ratio Complexity in Standardbred Racehorses From Rest to Maximal Effort: Insights Into Arrhythmia Risk. J Vet Intern Med 2025 Sep-Oct;39(5):e70207.
    doi: 10.1111/jvim.70207pubmed: 40926462google scholar: lookup
  5. Maas LT, Morgan JM, Case J, Chell DD, McLean AK. Pilot Study: Heart Rate and Heart Rate Variability Indices in Mules Evaluated by 24-Hour Electrocardiogram. Animals (Basel) 2025 Aug 20;15(16).
    doi: 10.3390/ani15162438pubmed: 40867766google scholar: lookup
  6. Avison A, Physick-Sheard PW, Pyle WG. Performance horses as a model for exercise-associated cardiac arrhythmias and sudden cardiac death. J Mol Cell Cardiol Plus 2025 Jun;12:100452.
    doi: 10.1016/j.jmccpl.2025.100452pubmed: 40475708google scholar: lookup
  7. Nissen SD, Saljic A, Carstensen H, Braunstein TH, Hesselkilde EM, Kjeldsen ST, Hopster-Iversen C, D'Souza A, Jespersen T, Buhl R. Muscarinic acetylcholine receptors M(2) are upregulated in the atrioventricular nodal tract in horses with a high burden of second-degree atrioventricular block. Front Cardiovasc Med 2023;10:1102164.
    doi: 10.3389/fcvm.2023.1102164pubmed: 38034369google scholar: lookup