Skip to main content
SpringerLink
Log in

Brain-Heart Communication

Hardware and Software Strategies Through Nerves and Humoral Factors

  • Living reference work entry
  • First Online:
Book cover Brain and Heart Dynamics

Abstract

The tight crosstalk between heart and brain is becoming increasingly recognized as the underlying mutual mechanisms are better identified, having a potential impact for clinical approach. Cardiac control is achieved by means of a three-level hierarchical neuronal network (central nervous system neurons, extracardiac-intrathoracic neurons, and intrinsic cardiac nervous system), where all the components work together to fulfill the physiological demands. However, each component of this network can undergo pathologic-mediated changes due to the transduction of altered sensory inputs originating from a deteriorating heart. A key role in the maintenance of cardiovascular homeostasis is played by the autonomic nervous system with its sympathetic and parasympathetic branches, which operate in a reciprocal manner. Heart rate best mirrors the relative balance between these two systems, and especially heart rate variability has emerged as a key parameter that reflects the health status of a given individual. Neural reflexes (i.e., the baroreceptor reflex) and several neuromodulators released from the heart itself or coming from other sites, as well as neurotrophins, also contribute to cardiovascular homeostasis and will be considered in the present chapter. A deeper understanding of heart-brain interactions will facilitate the prompt recognition and management of cardiac diseases, as well as of neurologic disorders associated to heart dysfunction, and, at the same time, will help in optimizing the therapeutic approach.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Tahsili-Fahadan P, Geocadin RG. Heart-Brain axis: effects of neurologic injury on cardiovascular function. Circ Res. 2017;120(3):559–72.

    Article  CAS  PubMed  Google Scholar 

  2. Fontes MA, Filho ML, Santos Machado NL et al. Asymmetric sympathetic output: the dorsomedial hypothalamus as a potential link between emotional stress and cardiac arrhythmias. Auton Neurosci. 2017;207:22. pii:S1566-0702(16)30228-4.

    Article  PubMed  Google Scholar 

  3. Mittleman MA, Maclure M, Sherwood JB, et al. Triggering of acute myocardial infarction onset by episodes of anger. Determinants of Myocardial Infarction Onset Study Investigators. Circulation. 1995;92(7):1720–17254.

    Article  CAS  PubMed  Google Scholar 

  4. Lampert R, Shusterman V, Burg M, et al. Anger-induced T-wave alternans predicts future ventricular arrhythmias in patients with implantable cardioverter-defibrillators. J Am Coll Cardiol. 2009;53(9):774–8.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Leor J, Poole WK, Kloner RA. Sudden cardiac death triggered by an earthquake. N Engl J Med. 1996;334:413–9.

    Article  CAS  PubMed  Google Scholar 

  6. Wilbert-Lampen U, Leistner D, Greven S, et al. Cardiovascular events during World Cup soccer. N Engl J Med. 2008;358(5):475–83.

    Article  CAS  PubMed  Google Scholar 

  7. Lampert R, Rosenfeld L, Batsford W, et al. Circadian variation of sustained ventricular tachycardia in patients with coronary artery disease and implantable cardioverter-defibrillators. Circulation. 1994;90:241–7.

    Article  CAS  PubMed  Google Scholar 

  8. Tofler GH, Gebara OC, Mittleman MA, et al. Morning peak in ventricular tachyarrhythmias detected by the time of implantable cardiverter-defibrillator therapy. Circulation. 1995;92:1203–8.

    Article  CAS  PubMed  Google Scholar 

  9. Peters RW, McQuillan S, Resnick SK, et al. Increased Monday incidence of lifethreatening ventricular arrhythmias. Circulation. 1996;94:1346–9.

    Article  CAS  PubMed  Google Scholar 

  10. Warnert EA, Hart EC, Hall JE, et al. The major cerebral arteries proximal to the Circle of Willis contribute to cerebrovascular resistance in humans. J Cereb Blood Flow Metab. 2016;36(8):1384–95.

    Article  PubMed  Google Scholar 

  11. van der Wall EE. New insights in prevention, diagnosis and treatment of stroke: its relation with atrial fibrillation. Neth Hear J. 2012;20(4):141–2.

    Article  Google Scholar 

  12. Verheugt FW. Antithrombotic therapy in heart failure. Neth Hear J. 2012;20(4):176–8.

    Article  CAS  Google Scholar 

  13. van der Wall EE, van Gilst WH. Neurocardiology: close interaction between heart and brain. Neth Hear J. 2013;21(2):51–2.

    Article  Google Scholar 

  14. Chatterjee S. ECG changes in subarachnoid haemorrhage: a synopsis. Neth Hear J. 2011;19(1):31–4.

    Article  CAS  Google Scholar 

  15. Talman WT. Cardiovascular regulation and lesions on the central nervous system. Ann Neurol. 1985;18(1):1–13.

    Article  CAS  PubMed  Google Scholar 

  16. Adams HP Jr, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation. 2007;115(20):e478–534.

    Article  PubMed  Google Scholar 

  17. Palma JA, Benarroch EE. Neural control of the heart. Recent concepts and clinical correlations. Neurology. 2014;8(3):261–71.

    Article  Google Scholar 

  18. Ardell JL, Armour JA. Neurocardiology: structure-based function. Compr Physiol. 2016;6(4):1635–53.

    Article  PubMed  Google Scholar 

  19. Oppenheimer SM, Saleh TM, Wilson JX, et al. Plasma and organ catecholamine levels following stimulation of the rat insular cortex. Brain Res. 1992;569(2):221–8.

    Article  CAS  PubMed  Google Scholar 

  20. Oppenheimer S, Cechetto D. The insular cortex and the regulation of cardiac function. Compr Physiol. 2016;6(2):1081–133.

    Article  PubMed  Google Scholar 

  21. Kawashima T. The autonomic nervous system of the human heart with special reference to its origin, course, and peripheral distribution. Anat Embryol. 2005;209:425–38.

    Article  Google Scholar 

  22. Hoover DB, Ganote CE, Ferguson SM, et al. Localization of cholinergic innervation in guinea pig heart by immunohistochemistry for high-affinity choline transporters. Cardiovasc Res. 2004;62(1):112–21.

    Article  CAS  PubMed  Google Scholar 

  23. Gatti PJ, Johnson TA, Phan P, et al. The physiological and anatomical demonstration of functionally selective parasympathetic ganglia located in discrete fat pads on the feline myocardium. J Auton Nerv Syst. 1995;51(3):255–9.

    Article  CAS  PubMed  Google Scholar 

  24. Armour JA. The little brain on the heart. Cleve Clin J Med. 2007;74(Suppl 1):S48–51.

    Article  PubMed  Google Scholar 

  25. Wake E, Brack K. Characterization of the intrinsic cardiac nervous system. Auton Neurosci. 2016;199:3–16.

    Article  PubMed  Google Scholar 

  26. Pius-Sadowska E, Machaliński B. BDNF – a key player in cardiovascular system. J Mol Cell Cardiol. 2017;110:54–60.

    Article  CAS  PubMed  Google Scholar 

  27. Fukuda K, Kanazawa H, Aizawa Y, et al. Cardiac innervation and sudden cardiac death. Circ Res. 2015;116(12):2005–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Choi EK, Chen PS. Is the atrial neural plexis a therapeutic target in atrial fibrillation? Methodist Debakey Cardiovasc J. 2015;11(2):82–6.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Singh S, Sayers S, Walter JS, et al. Hypertrophy of neurons within cardiac ganglia in human, canine, and rat heart failure: the potential role of nerve growth factor. J Am Heart Assoc. 2013;2(4):e000210.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Hasan W. Autonomic cardiac innervation: development and adult plasticity. Organogenesis. 2013;9(3):176–93.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Bers DM. Cardiac excitation-contraction coupling. Nature. 2002;415(6868):198–205.

    Article  CAS  PubMed  Google Scholar 

  32. Marx SO, Kurokawa J, Reiken S, et al. Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel. Science. 2002;295(5554):496–9.

    Article  CAS  PubMed  Google Scholar 

  33. Accili EA, Proenza C, Baruscotti M, et al. From funny current to HCN channels: 20 years of excitation. News Physiol Sci. 2002;17:32–7.

    CAS  PubMed  Google Scholar 

  34. Tsien RW. Cyclic AMP and contractile activity in heart. Adv Cyclic Nucleotide Res. 1977;8:363–420.

    CAS  PubMed  Google Scholar 

  35. Harvey RD, Belevych AE. Muscarinic regulation of cardiac ion channels. Br J Pharmacol. 2003;139(6):1074–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Fernández-Falgueras A, Sarquella-Brugada G, Brugada J, et al. Cardiac channelopathies and sudden death: recent clinical and genetic advances. Biology (Basel). 2017;6(1). pii: E7

    Google Scholar 

  37. Schwartz PJ, Ackerman MJ, Wilde AAM. Channelopathies as causes of sudden cardiac death. Card Electrophysiol Clin. 2017;9(4):537–49.

    Article  PubMed  Google Scholar 

  38. Levy MN. Sympathetic – parasympathetic interactions in the heart. Circ Res. 1971;29(5):437–45.

    Article  CAS  PubMed  Google Scholar 

  39. Cheng X, Ji Z, Tsalkova T, Mei F. Epac and PKA: a tale of two intracellular cAMP receptors. Acta Biochim Biophys Sin Shanghai. 2008;40(7):651–62.

    Article  CAS  PubMed  Google Scholar 

  40. Fujita T, Umemura M, Yokoyama U, et al. The role of Epac in the heart. Cell Mol Life Sci. 2017;74(4):591–606.

    Article  CAS  PubMed  Google Scholar 

  41. Schmidt M, Dekker FJ, Maarsingh H. Exchange protein directly activated by cAMP (epac): a multidomain cAMP mediator in the regulation of diverse biological functions. Pharmacol Rev. 2013;65(2):670–709.

    Article  PubMed  CAS  Google Scholar 

  42. Schlicker E, Feuerstein T. Human presynaptic receptors. Pharmacol Ther. 2017;172:1–21.

    Article  CAS  PubMed  Google Scholar 

  43. Shaffer F, McCraty R, Zerr CL. A healthy heart is not a metronome: an integrative review of the heart’s anatomy and heart rate variability. Front Psychol. 2014;5:1040.

    Article  PubMed  PubMed Central  Google Scholar 

  44. McCraty R, Shaffer F. Heart rate variability: new perspectives on physiological mechanisms, assessment of self-regulatory capacity, and health risk. Glob Adv Health Med. 2015;4(1):46–61.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Wolf MM, Varigos GA, Hunt D, Sloman JG. Sinus arrhythmia in acute myocardial infarction. Med J Aust. 1978;2(2):52–3.

    CAS  PubMed  Google Scholar 

  46. Huikuri HV, Jokinen V, Syvänne M, et al. Heart rate variability and progression of coronary atherosclerosis. Arterioscler Thromb Vasc Biol. 1999;9(8):1979–85.

    Article  Google Scholar 

  47. Brown L, Karmakar C, Gray R, et al. Heart rate variability alterations in late life depression: a meta-analysis. J Affect Disord. 2018;235:456–66.

    Article  PubMed  Google Scholar 

  48. Umetani K, Singer DH, McCraty R, Atkinson M. Twenty-four hour time domain heart rate variability and heart rate: relations to age and gender over nine decades. J Am Coll Cardiol. 1998;31(3):593–601.

    Article  CAS  PubMed  Google Scholar 

  49. Kimmerly DS. A review of human neuroimaging investigations involved with central autonomic regulation of baroreflex-mediated cardiovascular control. Auton Neurosci. 2017;207:10. pii: S1566-0702(17)30117-0.

    Article  PubMed  Google Scholar 

  50. Monahan KD. Effect of aging on baroreflex function in humans. Am J Phys Regul Integr Comp Phys. 2007;293(1):R3–12.

    CAS  Google Scholar 

  51. Sykora M, Diedler J, Rupp A, et al. Impaired baroreceptor reflex sensitivity in acute stroke is associated with insular involvement, but not with carotid atherosclerosis. Stroke. 2009;40:737–74.

    Article  PubMed  Google Scholar 

  52. Pascale A, Govoni S. Cerebral aging: implications for the heart autonomic nervous system regulation. In: Gronda E, Vanoli E, Costea A, editors. Heart failure management: the neural pathways. Cham: Springer International Publishing; 2016. p. 115–27.

    Chapter  Google Scholar 

  53. De Lucia C, Femminella GD, Gambino G, et al. Adrenal adrenoceptors in heart failure. Front Physiol. 2014;5:246.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Haase M, Willenberg HS, Bornstein SR. Update on the corticomedullary interaction in the adrenal gland. Endocr Dev. 2011;20:28–37.

    Article  CAS  PubMed  Google Scholar 

  55. Hodel A. Effects of glucocorticoids on adrenal chromaffin cells. J Neuroendocrinol. 2001;13(2):216–20.

    Article  CAS  PubMed  Google Scholar 

  56. Flügge G, van Kampen M, Meyer H, et al. Alpha2A and alpha2C-adrenoceptor regulation in the brain: alpha2A changes persist after chronic stress. Eur J Neurosci. 2003;17(5):917–28.

    Article  PubMed  Google Scholar 

  57. Port JD, Bristow MR. Altered beta-adrenergic receptor gene regulation and signaling in chronic heart failure. J Mol Cell Cardiol. 2001;33(5):887–905.

    Article  CAS  PubMed  Google Scholar 

  58. Tigerstedt R, Bergman PG. Niere und kreislauf. Skand Arch Physiol. 1898;8:223–71.

    Article  Google Scholar 

  59. Yang T, Xu C. Physiology and pathophysiology of the intrarenal renin-angiotensin system: an update. J Am Soc Nephrol. 2017;28(4):1040–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. De Mello WC. Local renin angiotensin aldosterone systems and cardiovascular diseases. Med Clin North Am. 2017;101(1):117–27.

    Article  PubMed  Google Scholar 

  61. Kawada T, Yamazaki T, Akiyama T, et al. Angiotensin II attenuates myocardial interstitial acetylcholine release in response to vagal stimulation. Am J Physiol Heart Circ Physiol. 2007;293(4):H2516–22.

    Article  CAS  PubMed  Google Scholar 

  62. Serneri GG, Boddi M, Cecioni I, et al. Cardiac angiotensin II formation in the clinical course of heart failure and its relationship with left ventricular function. Circ Res. 2001;88(9):961–8.

    Article  CAS  PubMed  Google Scholar 

  63. Danser AH, van Kesteren CA, Bax WA, et al. Prorenin, renin, angiotensinogen, and angiotensin-converting enzyme in normal and failing human hearts. Evidence for renin binding. Circulation. 1997;96(1):220–6.

    Article  CAS  PubMed  Google Scholar 

  64. De Mello WC. Intracellular renin alters the electrical properties of the intact heart ventricle of adult Sprague Dawley rats. Regul Pept. 2013;181:45–9.

    Article  PubMed  CAS  Google Scholar 

  65. Leenen F, Blaustein MP, Hamlyn J. Update on angiotensin II: new endocrine connections between the brain, adrenal glands and the cardiovascular system. Endocr Connect. 2017;6(7):R131–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Santos RA, Simoes e Silva AC, Maric C, et al. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A. 2003;100(14):8258–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Zini S, Fournie-Zaluski MC, Chauvel E, et al. Identification of metabolic pathways of brain angiotensin II and III using specific aminopeptidase inhibitors: predominant role of angiotensin III in the control of vasopressin release. Proc Natl Acad Sci U S A. 1996;93(21):11968–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Huang BS, Zheng H, Tan J, et al. Regulation of hypothalamic renin-angiotensin system and oxidative stress by aldosterone. Exp Physiol. 2011;96(10):1028–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Uijl E, Ren L, Danser AHJ. Angiotensin generation in the brain: a re-evaluation. Clin Sci (Lond). 2018;132(8):839–50.

    Article  CAS  Google Scholar 

  70. von Lueder TG, Atar D, Krum H. Current role of neprilysin inhibitors in hypertension and heart failure. Pharmacol Ther. 2014;144(1):41–9.

    Article  CAS  Google Scholar 

  71. Suga SI, Itoh H, Komatsu Y, et al. Regulation of endothelial production of C-type natriuretic peptide by interaction between endothelial cells and macrophages. Endocrinology. 1998;139(4):1920–6.

    Article  CAS  PubMed  Google Scholar 

  72. Santhekadur PK, Kumar DP, Seneshaw M, et al. The multifaceted role of natriuretic peptides in metabolic syndrome. Biomed Pharmacother. 2017;92:826–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Havakuk O, Elkayam U. Angiotensin receptor-neprilysin inhibition. J Cardiovasc Pharmacol Ther. 2017;22(4):356–64.

    Article  CAS  PubMed  Google Scholar 

  74. Nishikimi T, Maeda N, Matsuoka H. The role of natriuretic peptides in cardio protection. Cardiovasc Res. 2006;69:318–28.

    Article  CAS  PubMed  Google Scholar 

  75. Volpe M. Natriuretic peptides and cardio-renal disease. Int J Cardiol. 2014;176:630–9.

    Article  PubMed  Google Scholar 

  76. Yoshimura M, Yasue H, Ogawa H. Pathophysiological significance and clinical application of ANP and BNP in patients with heart failure. Can J Physiol Pharmacol. 2001;79:730–5.

    Article  CAS  PubMed  Google Scholar 

  77. Pandit K, Mukhopadhyay P, Ghosh S, et al. Natriuretic peptides: diagnostic and therapeutic use. Indian J Endocrinol Metab. 2011;15:S345–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Rubattu S, Triposkiadis F. Resetting the neurohormonal balance in heart failure (HF): the relevance of the natriuretic peptide (NP) system to the clinical management of patients with HF. Heart Fail Rev. 2017;22(3):279–88.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Caporali A, Emanueli C. Cardiovascular actions of neurotrophins. Physiol Rev. 2009;89:279–308.

    Article  CAS  PubMed  Google Scholar 

  80. Bothwell M. NGF, BDNF, NT3, and NT4. Handb Exp Pharmacol. 2014;220:3–15.

    Article  CAS  PubMed  Google Scholar 

  81. Govoni S, Pascale A, Amadio M, et al. NGF and heart: is there a role in heart disease? Pharmacol Res. 2011;63(4):266–77.

    Article  CAS  PubMed  Google Scholar 

  82. Skaper SD. The biology of neurotrophins, signalling pathways, and functional peptide mimetics of neurotrophins and their receptors. CNS Neurol Disord Drug Targets. 2008;7:46–62.

    Article  CAS  PubMed  Google Scholar 

  83. Scott-Solomon E, Kuruvilla R. Mechanisms of neurotrophin trafficking via Trk receptors. Mol Cell Neurosci. 2018;91:25. pii: S1044-7431(18)30014–30019.

    Article  CAS  PubMed  Google Scholar 

  84. Causing CG, Gloster A, Aloyz R, et al. Synaptic innervation density is regulated by neuron-derived BDNF. Neuron. 1997;18(2):257–67.

    Article  CAS  PubMed  Google Scholar 

  85. Wan R, Weigand LA, Bateman R, et al. Evidence that BDNF regulates heart rate by a mechanism involving increased brainstem parasympathetic neuron excitability. J Neurochem. 2014;129(4):573–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Wang H, Zhou XF. Injection of brain-derived neurotrophic factor in the rostral ventrolateral medulla increases arterial blood pressure in anaesthetized rats. Neuroscience. 2002;112(4):967–75.

    Article  CAS  PubMed  Google Scholar 

  87. Yang B, Slonimsky JD, Birren SJ. A rapid switch in sympathetic neurotransmitter release properties mediated by the p75 receptor. Nat Neurosci. 2002;5(6):539–45.

    Article  CAS  PubMed  Google Scholar 

  88. Hildreth V, Anderson RH, Henderson DJ. Autonomic innervation of the developing heart: origins and function. Clin Anat. 2009;22(1):36–46.

    Article  PubMed  Google Scholar 

  89. Hasan W, Smith PG. Nerve growth factor expression in parasympathetic neurons: regulation by sympathetic innervation. Eur J Neurosci. 2000;12:4391–7.

    Article  CAS  PubMed  Google Scholar 

  90. Meloni M, Caporali A, Graiani G, et al. Nerve growth factor promotes cardiac repair following myocardial infarction. Circ Res. 2010;106(7):1275–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. D’Elia E, Pascale A, Marchesi N, et al. Novel approaches to the post-myocardial infarction/heart failure neural remodeling. Heart Fail Rev. 2014;19(5):611–9.

    Article  PubMed  CAS  Google Scholar 

  92. Hassankhani A, Steinhelper ME, Soonpaa MH, et al. Overexpression of NGF within the heart of transgenic mice causes hyperinnervation, cardiac enlargement, and hyperplasia of ectopic cells. Dev Biol. 1995;169(1):309–21.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Drug Sciences, Section of Pharmacology, University of Pavia, Pavia, Italy

    Alessia Pascale & Stefano Govoni

Authors
  1. Alessia Pascale
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stefano Govoni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alessia Pascale .

Editor information

Editors and Affiliations

  1. Dept of Drug Sciences, Pharmacology Sect, University of Pavia, Dept of Drug Sciences, Pharmacology Sect, Pavia, Pavia, Italy

    Stefano Govoni

  2. Dept of Brain and Behavioural Sciences, University of Pavia Dept of Brain and Behavioural Sciences, Pavia, Pavia, Italy

    Pierluigi Politi

  3. Department of Molecular Medicine, University of Pavia, Department of Molecular Medicine, Pavia, Pavia, Italy

    Emilio Vanoli

Section Editor information

  1. Department of Drug Sciences, Section of Pharmacology, University of Pavia, Pavia, Italy

    Alessia Pascale

  2. Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy

    Emilia d'Elia

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Pascale, A., Govoni, S. (2019). Brain-Heart Communication. In: Govoni, S., Politi, P., Vanoli, E. (eds) Brain and Heart Dynamics. Springer, Cham. https://doi.org/10.1007/978-3-319-90305-7_4-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-90305-7_4-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-90305-7

  • Online ISBN: 978-3-319-90305-7

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation