russjcardiolРоссийский кардиологический журналRussian Journal of Cardiology1560-40712618-7620«SILICEA-POLIGRAF» LLC10.15829/1560-4071-2013-4-52-63russjcardiol-404Research ArticleК 50-ЛЕТИЮ РОССИЙСКОГО КАРДИОЛОГИЧЕСКОГО ОБЩЕСТВАTO THE 50th ANNIVERSARY OF THE RUSSIAN SOCIETY OF CARDIOLOGYВЕГЕТАТИВНАЯ НЕРВНАЯ СИСТЕМА ПРИ АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИИ И СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТИ: СОВРЕМЕННОЕ ПОНИМАНИЕ ПАТОФИЗИОЛОГИЧЕСКОЙ РОЛИ И НОВЫЕ ПОДХОДЫ К ЛЕЧЕНИЮAutonomic nervous system in arterial hypertension and heart failure: current understanding of its pathophysiologic role and innovative treatment approachesКонрадиА. О.KonradiA. O.

д. м.н., профессор, заместитель директора по научно-исследовательской работе, заведующая НИО артериальных гипертензий

konradi@almazovcentre.ruФГБУ Федеральный Центр сердца, крови и эндокринологии им. В. А. Алмазова, Минздрава России, Санкт-Петербург, РоссияРоссияV. A. Almazov Federal Centre of Heart, Blood, and Endocrinology, St. Petersburg, RussiaRussian Federation201328082013045263Copyright © Конради А.О., 20132013Конради А.О.Konradi A.O.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://russjcardiol.elpub.ru/jour/article/view/404

В обзоре представлено современное состояние понимания проблемы роли вегетативной дисфункции в развитии артериальной гипертензии и сердечной недостаточности и инновационные методы воздействия на различные компоненты вегетативной нервной системы с целью лечения сердечно-сосудистых заболеваний.

This review presents the modern understanding of the role of autonomic nervous system dysfunction in the development of arterial hypertension and heart failure. It also discusses the innovative treatment approaches which target various components of autonomic nervous system in order to treat cardiovascular disease.

вегетативная нервная системаартериальная гипертензиясердечная недостаточностьбарорефлексautonomic nervous systemarterial hypertensionheart failurebaroreflexReferencesMark A. L. The sympathetic nervous system in hypertension: a potential long-term regulator of arterial pressure. J Hypertens Suppl. 1996; 14: S159–65.Mark A. L. The sympathetic nervous system in hypertension: a potential long-term regulator of arterial pressure. J Hypertens Suppl. 1996; 14: S159–65.Shepherd J. T., Mancia G. Reflex control of the human cardiovascular system// Rev Physiol Biochem Pharmacol. 1996; 105:1–99.Shepherd J. T., Mancia G. Reflex control of the human cardiovascular system// Rev Physiol Biochem Pharmacol. 1996; 105:1–99.Grassi G., Cattaneo B. M., Seravalle G., et al. Baroreflex control of sympathetic nerve activity in essential and secondary hypertension. Hypertension. 1998; 31:68–72.Grassi G., Cattaneo B. M., Seravalle G., et al. Baroreflex control of sympathetic nerve activity in essential and secondary hypertension. Hypertension. 1998; 31:68–72.Hamilton WF & Richards DW (1982). Output of the heart. In Circulation of the Blood. Men and Ideas, ed. Fishman AP & Richards DW, pp. 87–90. American Physiological Society.Hamilton WF & Richards DW (1982). Output of the heart. In Circulation of the Blood. Men and Ideas, ed. Fishman AP & Richards DW, pp. 87–90. American Physiological Society.Grassi G. Assessment of Sympathetic cardiovascular drive in human hypertension: achievements and perspectives. Hypertension 2009; 54:690–7.Grassi G. Assessment of Sympathetic cardiovascular drive in human hypertension: achievements and perspectives. Hypertension 2009; 54:690–7.Grassi G., Colombo M., Seravalle G., et al. Dissociation between muscle and skin sympathetic nerve activity in essential hypertension, obesity, and congestive heart failure. Hypertension. 1998; 31:64–7.Grassi G., Colombo M., Seravalle G., et al. Dissociation between muscle and skin sympathetic nerve activity in essential hypertension, obesity, and congestive heart failure. Hypertension. 1998; 31:64–7.Vaz M., Jennings G., Turner A., et al. Regional sympathetic nervous activity and oxygen consumption in obese normotensive human subjects. Circulation. 1997; 96:3423–9.Vaz M., Jennings G., Turner A., et al. Regional sympathetic nervous activity and oxygen consumption in obese normotensive human subjects. Circulation. 1997; 96:3423–9.Burns J., Sivananthan M. U., Ball S. G., et al. Relationship between central sympathetic drive and magnetic resonance imaging-determined left ventricular mass in essential hypertension. Circulation. 2007; 115:1999–2005.Burns J., Sivananthan M. U., Ball S. G., et al. Relationship between central sympathetic drive and magnetic resonance imaging-determined left ventricular mass in essential hypertension. Circulation. 2007; 115:1999–2005.Strand A. H., Gudmundsdottir H., Os I., et al. Arterial plasma noradrenaline predicts left ventricular mass independently of blood pressure and body build in men who develop hypertension over 20 years. J Hypertens. 2006; 24:905–13.Strand A. H., Gudmundsdottir H., Os I., et al. Arterial plasma noradrenaline predicts left ventricular mass independently of blood pressure and body build in men who develop hypertension over 20 years. J Hypertens. 2006; 24:905–13.Mancia G., Grassi G., Giannattasio C., et al. Sympathetic activation in the pathogenesis of hypertension and progression of organ damage. Hypertension. 1999; 34:724–8.Mancia G., Grassi G., Giannattasio C., et al. Sympathetic activation in the pathogenesis of hypertension and progression of organ damage. Hypertension. 1999; 34:724–8.DiBona G. F., Kopp U. C. Neural control of renal function. Physiol Rev. 1997; 77:75–197.DiBona G. F., Kopp U. C. Neural control of renal function. Physiol Rev. 1997; 77:75–197.Converse R. L. Jr, Jacobsen T. N., Toto R. D., et al. Sympathetic overactivity in patients with chronic renal failure. N Engl J Med. 1992; 327:1912–8.Converse R. L. Jr, Jacobsen T. N., Toto R. D., et al. Sympathetic overactivity in patients with chronic renal failure. N Engl J Med. 1992; 327:1912–8.Zoccali C., Mallamaci F., Parlongo S., et al. Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease. Circulation. 2002; 105:1354–9.Zoccali C., Mallamaci F., Parlongo S., et al. Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease. Circulation. 2002; 105:1354–9.Qvisth V., Hagstr m-Toft E., Enoksson S., et al. Catecholamine regulation of local lactate production in vivo in skeletal muscle and adipose tissue: role of adrenoreceptor subtypes. J Clin Endocrinol Metab. 2008; 93:240–6.Qvisth V., Hagstr m-Toft E., Enoksson S., et al. Catecholamine regulation of local lactate production in vivo in skeletal muscle and adipose tissue: role of adrenoreceptor subtypes. J Clin Endocrinol Metab. 2008; 93:240–6.Lambert E., Dawood T., Schlaich M., et al. Single-unit sympathetic discharge pattern in pathological conditions associated with elevated cardiovascular risk. Clin Exp Pharmacol Physiol. 2008; 35:503–7.Lambert E., Dawood T., Schlaich M., et al. Single-unit sympathetic discharge pattern in pathological conditions associated with elevated cardiovascular risk. Clin Exp Pharmacol Physiol. 2008; 35:503–7.Wallin B. G., Kunimoto M. M., Sellgren J. Possible genetic influence on the strength of human muscle sympathetic activity at rest. Hypertension. 1993; 22:282–4.Wallin B. G., Kunimoto M. M., Sellgren J. Possible genetic influence on the strength of human muscle sympathetic activity at rest. Hypertension. 1993; 22:282–4.Miller J. W., Keogh J. M., Henning E., et al. Modulation of blood pressure by central melonocortinergic pathways. N Engl J Med. 2009; 360:44–52.Miller J. W., Keogh J. M., Henning E., et al. Modulation of blood pressure by central melonocortinergic pathways. N Engl J Med. 2009; 360:44–52.Zubcevic J., Waki H., Raizada M. K., et al. Autonomic-Immune-Vascular Interaction: An Emerging Concept for Neurogenic Hypertension. 2011; 57:1026–33.Zubcevic J., Waki H., Raizada M. K., et al. Autonomic-Immune-Vascular Interaction: An Emerging Concept for Neurogenic Hypertension. 2011; 57:1026–33.Cowley A. W., Jr.б Liard JF, Guyton AC. Role of baroreceptor reflex in daily control of arterial blood pressure and other variables in dogs. Circulation Research. 1973; 32 (5):564–76.Cowley A. W., Jr.б Liard JF, Guyton AC. Role of baroreceptor reflex in daily control of arterial blood pressure and other variables in dogs. Circulation Research. 1973; 32 (5):564–76.Doumas M., Douma S. Interventional management of resistant hypertension. The Lancet. 2009; 373 (9671):1228–30.Doumas M., Douma S. Interventional management of resistant hypertension. The Lancet. 2009; 373 (9671):1228–30.Bilgutay A. M., Lillehei C. W. Surgical treatment of hypertension with reference to baropacing. Am J Cardiol. 1966; 17:663–7.Bilgutay A. M., Lillehei C. W. Surgical treatment of hypertension with reference to baropacing. Am J Cardiol. 1966; 17:663–7.Griffith L. S., Schwartz S. I. Reversal of renal hypertension by electrical stimulation of the carotid sinus nerve. Surgery. 1964; 56:232–9.Griffith L. S., Schwartz S. I. Reversal of renal hypertension by electrical stimulation of the carotid sinus nerve. Surgery. 1964; 56:232–9.Neistadt A., Schwartz S. I. Effects of electrical stimulation of the carotid sinus nerve in reversal of experimentally induced hypertension. Surgery. 1967; 61:923–31.Neistadt A., Schwartz S. I. Effects of electrical stimulation of the carotid sinus nerve in reversal of experimentally induced hypertension. Surgery. 1967; 61:923–31.Thrasher T. N. Effects of chronic baroreceptor unloading on blood pressure in the dog. American Journal of Physiology. 2005; 288: R863–71.Thrasher T. N. Effects of chronic baroreceptor unloading on blood pressure in the dog. American Journal of Physiology. 2005; 288: R863–71.Chapleau M. W., Hajduczok G., Abboud F. M. Mechanisms of resetting of arterial baroreceptors: an overview. American Journal of the Medical Sciences. 1988; 295 (4):327–34.Chapleau M. W., Hajduczok G., Abboud F. M. Mechanisms of resetting of arterial baroreceptors: an overview. American Journal of the Medical Sciences. 1988; 295 (4):327–34.Parsonnet V., Rothfeld E. L., Raman K. V., et al. Electrical stimulation of the carotid sinus nerve. Surg Clin North Am. 1969; 49:589–96.Parsonnet V., Rothfeld E. L., Raman K. V., et al. Electrical stimulation of the carotid sinus nerve. Surg Clin North Am. 1969; 49:589–96.Rothfeld E. L., Parsonnet V., Raman K. V., et al. The effect of carotid sinus nerve stimulation on cardiovascular dynamics in man. Angiology. 1969; 20:213–8.Rothfeld E. L., Parsonnet V., Raman K. V., et al. The effect of carotid sinus nerve stimulation on cardiovascular dynamics in man. Angiology. 1969; 20:213–8.Brest A. N. Carotid sinus nerve stimulation. Am J Cardiol. 1970; 26:328–9.Brest A. N. Carotid sinus nerve stimulation. Am J Cardiol. 1970; 26:328–9.Carlsten A., Folkow B., Grimby G., et al. Cardiovascular effects of direct stimulation of the carotid sinus nerve in man. Acta Physiol Scand. 1958; 44:138–45.Carlsten A., Folkow B., Grimby G., et al. Cardiovascular effects of direct stimulation of the carotid sinus nerve in man. Acta Physiol Scand. 1958; 44:138–45.Bilgutay A. M., Lillehei C. W. Treatment of hypertension with an implantable electronic device. JAMA. 1965; 191:649–53.Bilgutay A. M., Lillehei C. W. Treatment of hypertension with an implantable electronic device. JAMA. 1965; 191:649–53.Schwartz S., Griffith L., Neistadt A., et al. Chronic carotid sinus nerve stimulation in the treatment of essential hypertension. Am J Surg. 1967; 114:5–15.Schwartz S., Griffith L., Neistadt A., et al. Chronic carotid sinus nerve stimulation in the treatment of essential hypertension. Am J Surg. 1967; 114:5–15.Tuckman J., Reich T., Goodman B., et al.: Effects of radio frequency carotid sinus nerve stimulators in patients with severe hypertension [abstract]. Circulation 1966, 33 (Suppl III): III-231.Tuckman J., Reich T., Goodman B., et al.: Effects of radio frequency carotid sinus nerve stimulators in patients with severe hypertension [abstract]. Circulation 1966, 33 (Suppl III): III-231.Khatri I. M, Cohn J. N. Cardiac and peripheral vascular effects of carotid sinus nerve stimulation in hypertension in man. Clin Res. 1968; 16:235.Khatri I. M, Cohn J. N. Cardiac and peripheral vascular effects of carotid sinus nerve stimulation in hypertension in man. Clin Res. 1968; 16:235.Torresani J., Chevalier-Cholat A. M., Heuillet G., et al. Stimulation du nerf du dinus carotidien et hypertension art rielle. Acta Chir Belg. 1970; 69:33–41.Torresani J., Chevalier-Cholat A. M., Heuillet G., et al. Stimulation du nerf du dinus carotidien et hypertension art rielle. Acta Chir Belg. 1970; 69:33–41.Brest A. N., Wiener L., Bachrach B. Bilateral carotid sinus nerve stimulation in the treatment of hypertension. Am J Cardiol. 1972; 29:821–5.Brest A. N., Wiener L., Bachrach B. Bilateral carotid sinus nerve stimulation in the treatment of hypertension. Am J Cardiol. 1972; 29:821–5.Braunwald E., Epstein S. E., Glick G., et al. Relief of angina pectoris by electrical stimulation of the carotid-sinus nerves. N Engl J Med. 1967; 277:1278–83.Braunwald E., Epstein S. E., Glick G., et al. Relief of angina pectoris by electrical stimulation of the carotid-sinus nerves. N Engl J Med. 1967; 277:1278–83.Grassi G. Sympathetic deactivation as a goal of nonpharmacologic and pharmacologic antihypertensive treatment: rationale and options. Curr Hypertens Rep. 2003; 5:277–80.Grassi G. Sympathetic deactivation as a goal of nonpharmacologic and pharmacologic antihypertensive treatment: rationale and options. Curr Hypertens Rep. 2003; 5:277–80.Scheffers I., Schmidli J., Kroon A. A., et al. Sustained blood pressure reduction by baroreflex hypertension therapy with a chronically implanted system: 2-year data from the Rheos DEBUT-HT study in patients with resistant hypertension. Journal of Hypertension. 2008; 26 (supplement 1): p. S19.Scheffers I., Schmidli J., Kroon A. A., et al. Sustained blood pressure reduction by baroreflex hypertension therapy with a chronically implanted system: 2-year data from the Rheos DEBUT-HT study in patients with resistant hypertension. Journal of Hypertension. 2008; 26 (supplement 1): p. S19.Peters T. K., Koralewski H. E., Zerbst E. The principle of electrical carotid sinus nerve stimulation: a nerve pacemaker system for angina pectoris and hypertension therapy. Ann Biomed Eng. 1980;8:445–58.Peters T. K., Koralewski H. E., Zerbst E. The principle of electrical carotid sinus nerve stimulation: a nerve pacemaker system for angina pectoris and hypertension therapy. Ann Biomed Eng. 1980;8:445–58.Lohmeier T. E., Irwin E. D., Rossing M. A., et al. Prolonged activation of the baroreflex produces sustained hypotension. Hypertension. 2004; 43:306–11.Lohmeier T. E., Irwin E. D., Rossing M. A., et al. Prolonged activation of the baroreflex produces sustained hypotension. Hypertension. 2004; 43:306–11.Schmidli J., Savolainen H., Eckstein F., et al. Acute device-based blood pressure reduction: electrical activation of the carotid baroreflex in patients undergoing elective carotid surgery. Vascular. 2007; 15:63–9.Schmidli J., Savolainen H., Eckstein F., et al. Acute device-based blood pressure reduction: electrical activation of the carotid baroreflex in patients undergoing elective carotid surgery. Vascular. 2007; 15:63–9.Scheffers I. J., Kroon A. A., Tordoir J. H., et al. Rheos Baroreflex Hypertension Therapy System to treat resistant hypertension. Expert Rev Med Devices. 2008; 5:33–9.Scheffers I. J., Kroon A. A., Tordoir J. H., et al. Rheos Baroreflex Hypertension Therapy System to treat resistant hypertension. Expert Rev Med Devices. 2008; 5:33–9.Sanchez L. A., Illig K., Levy M., et al. Implantable carotid sinus stimulator for the treatment of resistant hypertension: local effects on carotid artery morphology. Annals of Vascular Surgery. 2010; 24 (2):178–84.Sanchez L. A., Illig K., Levy M., et al. Implantable carotid sinus stimulator for the treatment of resistant hypertension: local effects on carotid artery morphology. Annals of Vascular Surgery. 2010; 24 (2):178–84.Lovett E. G., Shaefer J., Kaifman C. L. Chronic activation by the Pheos system: an overview of results from European and North American feasibility studies@ Conf Proc IEEE Eng Med Biol Soc. 2009; 2009:4626.Lovett E. G., Shaefer J., Kaifman C. L. Chronic activation by the Pheos system: an overview of results from European and North American feasibility studies@ Conf Proc IEEE Eng Med Biol Soc. 2009; 2009:4626.Lohmeier T. E., Dwyer T. M., Hildebrandt D. A., et al. Influence of prolonged baroreflex activation on arterial pressure in angiotensin hypertension. Hypertension. 2005; 46 (5):1194–200.Lohmeier T. E., Dwyer T. M., Hildebrandt D. A., et al. Influence of prolonged baroreflex activation on arterial pressure in angiotensin hypertension. Hypertension. 2005; 46 (5):1194–200.Lohmeier T. E., Dwyer T. M., Irwin E. D., et al. Prolonged activation of the baroreflex abolishes obesity-induced hypertension. Hypertension. 2007; 49 (6):1307–14.Lohmeier T. E., Dwyer T. M., Irwin E. D., et al. Prolonged activation of the baroreflex abolishes obesity-induced hypertension. Hypertension. 2007; 49 (6):1307–14.Schwartz S. I., Griffith L. S., Neistadt A., et al. Chronic carotid sinus nerve stimulation in the treatment of essential hypertension. Am J Surg. 1967; 114:5–15.Schwartz S. I., Griffith L. S., Neistadt A., et al. Chronic carotid sinus nerve stimulation in the treatment of essential hypertension. Am J Surg. 1967; 114:5–15.DiBona G. F., Kopp U. C. Neural control of renal function. Physiological Reviews. 1997; 77 (1):75–197.DiBona G. F., Kopp U. C. Neural control of renal function. Physiological Reviews. 1997; 77 (1):75–197.Campese VM, Kogosov E. Renal afferent denervation prevents hypertension in rats with chronic renal failure. Hypertension. 1995; 25 (4, part 2):878–82.Campese VM, Kogosov E. Renal afferent denervation prevents hypertension in rats with chronic renal failure. Hypertension. 1995; 25 (4, part 2):878–82.Kopp U. C., DiBona G. F. The neural control of renal function. In: Seldin G, Giebisch G, editors. The Kidney: Physiology and Pathophysiology. 3rd edition. New York, NY, USA: Raven Press; 2006. pp. 981–1006.Kopp U. C., DiBona G. F. The neural control of renal function. In: Seldin G, Giebisch G, editors. The Kidney: Physiology and Pathophysiology. 3rd edition. New York, NY, USA: Raven Press; 2006. pp. 981–1006.Barajas L., Liu L., Powers K. Anatomy of the renal innervation: intrarenal aspects and ganglia of origin. Canadian Journal of Physiology and Pharmacology. 1992; 70 (5):735–49.Barajas L., Liu L., Powers K. Anatomy of the renal innervation: intrarenal aspects and ganglia of origin. Canadian Journal of Physiology and Pharmacology. 1992; 70 (5):735–49.Luff S. E., Hengstberger S. G., McLachlan E. M., et al. Distribution of sympathetic neuroeffector junctions in the juxtaglomerular region of the rabbit kidney. Journal of the Autonomic Nervous System. 1992; 40 (3):239–54.Luff S. E., Hengstberger S. G., McLachlan E. M., et al. Distribution of sympathetic neuroeffector junctions in the juxtaglomerular region of the rabbit kidney. Journal of the Autonomic Nervous System. 1992; 40 (3):239–54.Sobotka P. A., Mahfoud F., Schlaich M. P., et al. Sympatho-renal axis in chronic disease. Clin Res Cardiol. 2011.Sobotka P. A., Mahfoud F., Schlaich M. P., et al. Sympatho-renal axis in chronic disease. Clin Res Cardiol. 2011.Page I. H., Heuer G. J. A surgical treatment of essential hypertension. The Journal of Clinical Investigation. 1935; 14:22–6.Page I. H., Heuer G. J. A surgical treatment of essential hypertension. The Journal of Clinical Investigation. 1935; 14:22–6.Smithwick R. H. Surgical treatment of hypertension. The American Journal of Medicine. 1948; 4 (5):744–59.Smithwick R. H. Surgical treatment of hypertension. The American Journal of Medicine. 1948; 4 (5):744–59.Isberg E. M., Peet M. M. The influence of supradiaphragmatic splanchnicectomy on the heart in hypertension. American Heart Journal. 1948; 35 (4):567–83.Isberg E. M., Peet M. M. The influence of supradiaphragmatic splanchnicectomy on the heart in hypertension. American Heart Journal. 1948; 35 (4):567–83.Allen E. V. Sympathectomy for essential hypertension. Circulation. 1952; 6 (1):131–40.Allen E. V. Sympathectomy for essential hypertension. Circulation. 1952; 6 (1):131–40.Krum H., Schlaich M., Whitbourn R., et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009; 373 (9671):1275–81.Krum H., Schlaich M., Whitbourn R., et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009; 373 (9671):1275–81.DiBona G. F., Esler M. Translational medicine: the antihypertensive effect of renal denervation. Am J Physiol Regul Integr Comp Physiol. 2010; 298 (2): R245–53.DiBona G. F., Esler M. Translational medicine: the antihypertensive effect of renal denervation. Am J Physiol Regul Integr Comp Physiol. 2010; 298 (2): R245–53.Doumas M., Douma S. Interventional management of resistant hypertension. The Lancet. 2009; 373 (9671):1228–30.Doumas M., Douma S. Interventional management of resistant hypertension. The Lancet. 2009; 373 (9671):1228–30.Katholi R. E., Rocha-Singh K. J., Goswami N. J., et al. Renal nerves in the maintenance of hypertension: a potential therapeutic target. Curr Hypertens Rep. 2010; 57:196–204.Katholi R. E., Rocha-Singh K. J., Goswami N. J., et al. Renal nerves in the maintenance of hypertension: a potential therapeutic target. Curr Hypertens Rep. 2010; 57:196–204.Symplicity HTN-1 Investigators. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension. 2011; 57:911–7.Symplicity HTN-1 Investigators. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension. 2011; 57:911–7.Mahfoud F., Schlaich M., Kindermann I., et al. Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study. Circulation. 2011 May 10; 123:1940–6.Mahfoud F., Schlaich M., Kindermann I., et al. Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study. Circulation. 2011 May 10; 123:1940–6.Schlaich M. P., Sobotka P. A., Krum H., et al. Renal sympathetic-nerve ablation for uncontrolled hypertension. The New England Journal of Medicine. 2009; 361:932–4.Schlaich M. P., Sobotka P. A., Krum H., et al. Renal sympathetic-nerve ablation for uncontrolled hypertension. The New England Journal of Medicine. 2009; 361:932–4.Symplicity HTN-2 Investigators, Esler M. D., Krum H., Sobotka P. A., et al. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010 Dec 4; 376:1903–9.Symplicity HTN-2 Investigators, Esler M. D., Krum H., Sobotka P. A., et al. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010 Dec 4; 376:1903–9.Voskuil M., Verloop W. L., Blankestijn P. J., et al. Percutaneous renal denervation for the treatment of resistant essential hypertension; the first Dutch experience. Neth Heart J. 2011; 19:319–23.Voskuil M., Verloop W. L., Blankestijn P. J., et al. Percutaneous renal denervation for the treatment of resistant essential hypertension; the first Dutch experience. Neth Heart J. 2011; 19:319–23.Witkowski A., Prejbisz A., Florczak E., et al. Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea. Hypertension. 2011; 58:167–77.Witkowski A., Prejbisz A., Florczak E., et al. Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea. Hypertension. 2011; 58:167–77.Pepper G. S., Lee R. W. Sympathetic activation in heart failure and its treatment with betablockade. Arch Intern Med. 1999; 159:225–34.Pepper G. S., Lee R. W. Sympathetic activation in heart failure and its treatment with betablockade. Arch Intern Med. 1999; 159:225–34.Dargie H. J., Lechat P. The cardiac insufficiency bisoprolol study (CIBIS-II): a randomized trial. Lancet. 1999; 353:9–13.Dargie H. J., Lechat P. The cardiac insufficiency bisoprolol study (CIBIS-II): a randomized trial. Lancet. 1999; 353:9–13.Merit-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/ XL randomized intervention trial in congestive heart failure (MERIT-HF). Lancet. 1999; 353:2001–7.Merit-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/ XL randomized intervention trial in congestive heart failure (MERIT-HF). Lancet. 1999; 353:2001–7.Eichorn E., Domanski M., Krause-Steinrauf H., et al.The beta-blocker evaluation of survival trial investigators. A trial of the beta–blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med. 2001; 344:1659–67.Eichorn E., Domanski M., Krause-Steinrauf H., et al.The beta-blocker evaluation of survival trial investigators. A trial of the beta–blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med. 2001; 344:1659–67.Packer M., Bristow M. R., Cohn J. N., et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med. 1996; 334:1349–55.Packer M., Bristow M. R., Cohn J. N., et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med. 1996; 334:1349–55.Packer M., Coats A. J., Fowler M. B., et al. Effect on carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001; 344:1651–8.Packer M., Coats A. J., Fowler M. B., et al. Effect on carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001; 344:1651–8.Giles T. D., Thomas M. G., Quiroz A., et al. Acute and short-term effects of clonidine in heart failure. Angiology. 1987; 38:537–48.Giles T. D., Thomas M. G., Quiroz A., et al. Acute and short-term effects of clonidine in heart failure. Angiology. 1987; 38:537–48.Issa Z. F., Ujhelyi M. R., Hildebrand K. R., et al. Intrathecal clonidine reduces the incidence of ischemia-provoked ventricular arrhythmias in a canine post infarction heart failure model. Heart Rhythm. 2005; 2:1122–7.Issa Z. F., Ujhelyi M. R., Hildebrand K. R., et al. Intrathecal clonidine reduces the incidence of ischemia-provoked ventricular arrhythmias in a canine post infarction heart failure model. Heart Rhythm. 2005; 2:1122–7.Cohn J. N., Pfeffer M. A., Rouleau J., et al. on behalf of the MOXCON Investigators. Adverse mortality effect of central sympathetic inhibition with sustained–release moxonidine in patients with heart failure (MOXCON). Eur J Heart Fail. 2003; 5:659–67.Cohn J. N., Pfeffer M. A., Rouleau J., et al. on behalf of the MOXCON Investigators. Adverse mortality effect of central sympathetic inhibition with sustained–release moxonidine in patients with heart failure (MOXCON). Eur J Heart Fail. 2003; 5:659–67.Behling A., Moraes R. S., Rohde L. E., et al. Cholinergic stimulation with pyridostigmine reduces ventricular arrhythmias and enhances heart rate variability in heart failure. Am Heart J. 2003; 146:494–500.Behling A., Moraes R. S., Rohde L. E., et al. Cholinergic stimulation with pyridostigmine reduces ventricular arrhythmias and enhances heart rate variability in heart failure. Am Heart J. 2003; 146:494–500.Mahajan A., Moore J., Cesario D. A. Use of thoracic epidural anesthesia for management of electrical storm: a case report. Heart Rhythm. 2005; 2:1359–62.Mahajan A., Moore J., Cesario D. A. Use of thoracic epidural anesthesia for management of electrical storm: a case report. Heart Rhythm. 2005; 2:1359–62.Southerland E. M., Milhorn D. M., Foreman R. D., et al. Preemptive, but not reactive, spinal cord stimulation mitigates transient ischemia induced myocardial infarction via cardiac adrenergic neurons. Am J Physiol Heart Circ Physiol. 2007; 292: H311–7.Southerland E. M., Milhorn D. M., Foreman R. D., et al. Preemptive, but not reactive, spinal cord stimulation mitigates transient ischemia induced myocardial infarction via cardiac adrenergic neurons. Am J Physiol Heart Circ Physiol. 2007; 292: H311–7.Issa Z. F., Zhou X., Ujhelyi M. R., et al. Thoracic spinal cord stimulation reduces the risk of ischemic ventricular arrhythmias in a post-infarction heart failure canine model. Circulation. 2005; 111:3217–20.Issa Z. F., Zhou X., Ujhelyi M. R., et al. Thoracic spinal cord stimulation reduces the risk of ischemic ventricular arrhythmias in a post-infarction heart failure canine model. Circulation. 2005; 111:3217–20.Lopshire J. C., Zhou X., Dusa C., et al. Spinal cord stimulation improves ventricular function and reduces ventricular arrhythmias in a canine postinfarction heart failure model. Circulation. 2009; 120:286–94.Lopshire J. C., Zhou X., Dusa C., et al. Spinal cord stimulation improves ventricular function and reduces ventricular arrhythmias in a canine postinfarction heart failure model. Circulation. 2009; 120:286–94.Determining the feasibility of spinal cord neuromodulation for he treatment of chronic heart failure (defeat-HF). Curr Cardiol Rep 2012 14:593–600.Determining the feasibility of spinal cord neuromodulation for he treatment of chronic heart failure (defeat-HF). Curr Cardiol Rep 2012 14:593–600.Spinal cord stimulation for heart failure (SCS HEART). Available t: http://clinicaltrials.gov/ct2/show/NCT01362725. Accessed 1 pr 2012.Spinal cord stimulation for heart failure (SCS HEART). Available t: http://clinicaltrials.gov/ct2/show/NCT01362725. Accessed 1 pr 2012.Neurostimulation of spinal nerves that affect the heart. Available t: http://clinicaltrials.gov/ct2/show/NCT01124136. Accessed 1 pr 2012.Neurostimulation of spinal nerves that affect the heart. Available t: http://clinicaltrials.gov/ct2/show/NCT01124136. Accessed 1 pr 2012.Vanoli E., De Ferrari G. M., Stramba-Badiale M., et al. Vagal stimulation and preventionof sudden death in conscious dogs with a healed myocardial infarction. Circ Res. 1991; 68:1471–81.Vanoli E., De Ferrari G. M., Stramba-Badiale M., et al. Vagal stimulation and preventionof sudden death in conscious dogs with a healed myocardial infarction. Circ Res. 1991; 68:1471–81.Li M., Zheng C., Sato T., et al. Vagal nerve stimulation markedly improves long-term survival after chronic heart failure in rats. Circulation. 2004;109:120–4.Li M., Zheng C., Sato T., et al. Vagal nerve stimulation markedly improves long-term survival after chronic heart failure in rats. Circulation. 2004;109:120–4.Zheng C., Li M., Inagaki M, et al. Vagal stimulation markedly suppresses arrhythmias in conscious rats with chronic heart failure after myocardial infarction. Conf Proc IEEE Eng Med Biol Soc. 2004; 7:7072–5.Zheng C., Li M., Inagaki M, et al. Vagal stimulation markedly suppresses arrhythmias in conscious rats with chronic heart failure after myocardial infarction. Conf Proc IEEE Eng Med Biol Soc. 2004; 7:7072–5.Zhang Y., Popovic Z. B., Bibevski S., et al. Chronic vagus nerve stimulation improves autonomic control and attenuates systemic inflammation and heart failure progression in a canine high–rate pacing model. Circulation. 2009; 2:692–9.Zhang Y., Popovic Z. B., Bibevski S., et al. Chronic vagus nerve stimulation improves autonomic control and attenuates systemic inflammation and heart failure progression in a canine high–rate pacing model. Circulation. 2009; 2:692–9.Sabbah H. N., Ilsar I., Zaretsky A., et al. Vagus nerve stimulation in experimental heart failure. Heart Fail Rev. 2011; 16:171–178.Sabbah H. N., Ilsar I., Zaretsky A., et al. Vagus nerve stimulation in experimental heart failure. Heart Fail Rev. 2011; 16:171–178.De Ferrari G. M., Ezra O. B., Ajmone-Marsan N, et al. Chronic vagal stimulation in patients with heart failure is feasible, safe and appears beneficial. Eur Heart J. 2006; 27:330–7.De Ferrari G. M., Ezra O. B., Ajmone-Marsan N, et al. Chronic vagal stimulation in patients with heart failure is feasible, safe and appears beneficial. Eur Heart J. 2006; 27:330–7.Schwartz P. J., Gaetano M., De Ferrari G. M. Vagal stimulation for heart failure: Background and first in–man study. Heart Rhythm. 2009; 6: S76–S81.Schwartz P. J., Gaetano M., De Ferrari G. M. Vagal stimulation for heart failure: Background and first in–man study. Heart Rhythm. 2009; 6: S76–S81.CardioFit™ for the treatment of heart failure. Available at: http:// clinicaltrials.gov/ct2/show/NCT00461019.CardioFit™ for the treatment of heart failure. Available at: http:// clinicaltrials.gov/ct2/show/NCT00461019.De Ferrari G. M., Crijns H. J., Borggrefe M., et al. Chronic vagus nerve stimulation; a new and promising therapeutic approach for chronic heart failure. Eur Heart J. 2011; 32 (7):847–55.De Ferrari G. M., Crijns H. J., Borggrefe M., et al. Chronic vagus nerve stimulation; a new and promising therapeutic approach for chronic heart failure. Eur Heart J. 2011; 32 (7):847–55.Increase of vagal tone in chf (inovate–hf). Available at: http://clinicaltrials.gov/ct2/show/NCT01303718.Increase of vagal tone in chf (inovate–hf). Available at: http://clinicaltrials.gov/ct2/show/NCT01303718.Neural cardiac therapy for heart failure study (NECTAR–HF). Available at: http://clinicaltrials.gov/ct2/show/NCT01385176.Neural cardiac therapy for heart failure study (NECTAR–HF). Available at: http://clinicaltrials.gov/ct2/show/NCT01385176.Filippone J. D., Bisognano J. D. Baroreflex stimulation in the treatment of hypertension. Curr Opin Nephrol Hypertens. 2007; 16:403–8.Filippone J. D., Bisognano J. D. Baroreflex stimulation in the treatment of hypertension. Curr Opin Nephrol Hypertens. 2007; 16:403–8.Heusser K., Tank J., Engeli S., et al. Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients. Hypertension. 2010; 55:619–26.Heusser K., Tank J., Engeli S., et al. Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients. Hypertension. 2010; 55:619–26.Sabbah H. N., Gupta R. C., Imai M, et al. Chronic electrical stimulation of the carotid sinus baroreflex improves left ventricular function and promotes reversal of ventricular remodeling in dogs with advanced heart failure. Circ Heart Fail. 2011; 4:65–70.Sabbah H. N., Gupta R. C., Imai M, et al. Chronic electrical stimulation of the carotid sinus baroreflex improves left ventricular function and promotes reversal of ventricular remodeling in dogs with advanced heart failure. Circ Heart Fail. 2011; 4:65–70.Rheos® diastolic heart failure trial. Available at: http://clinicaltrials. gov/ct2/show/NCT00718939.Rheos® diastolic heart failure trial. Available at: http://clinicaltrials. gov/ct2/show/NCT00718939.Lovett E. G., Schafer J., Kaufman C. L. Chronic baroreflex activation by the Rheos system: an overview of results from European and North American feasibility studies. Proceedings of the Engineering in Medicine and Biology Society, 2009 Annual International Conference of the IEEE, pp 4626–4630.Lovett E. G., Schafer J., Kaufman C. L. Chronic baroreflex activation by the Rheos system: an overview of results from European and North American feasibility studies. Proceedings of the Engineering in Medicine and Biology Society, 2009 Annual International Conference of the IEEE, pp 4626–4630.Baroreflex activation therapy in heart failure. Available at: http:// clinicaltrials.gov/ct2/show/NCT01484288.Baroreflex activation therapy in heart failure. Available at: http:// clinicaltrials.gov/ct2/show/NCT01484288.Georgakopoulos D., Little W. C., Abraham W. T., et al. Chronic baroreflex activation: a potential therapeutic approach to treat heart failure with preserved ejection fraction. J Card Fail. 2011; 17:167–78.Georgakopoulos D., Little W. C., Abraham W. T., et al. Chronic baroreflex activation: a potential therapeutic approach to treat heart failure with preserved ejection fraction. J Card Fail. 2011; 17:167–78.Rheos HOPE4HF trial. Available at: http://clinicaltrials.gov/ct2/ show/NCT00957073.Rheos HOPE4HF trial. Available at: http://clinicaltrials.gov/ct2/ show/NCT00957073.

The authors declare that there are no conflicts of interest present.