The Bezold-Jarisch reflex revisited: clinical implications of inhibitory reflexes originating in the heart

The concept of depressor reflexes originating in the heart was introduced by von Bezold in 1867 and was later revived by Jarisch. The Bezold-Jarisch reflex originates in cardiac sensory receptors with nonmyelinated vagal afferent pathways. The left ventricle, particularly the inferoposterior wall, is a principal location for these sensory receptors. Stimulation of these inhibitory cardiac receptors by stretch, chemical substances or drugs increases parasympathetic activity and inhibits sympathetic activity. These effects promote reflex bradycardia, vasodilation and hypotension (Bezold-Jarisch reflex) and also modulate renin release and vasopressin secretion. Conversely, decreases in the activity of these inhibitory sensory receptors reflexly increase sympathetic activity, vascular resistance, plasma renin activity and vasopressin. Long regarded as pharmacologic curiosities, it is now clear that reflexes originating in these inhibitory cardiac sensory receptors are important to the pathophysiology of many cardiovascular disorders. This paper reviews the role of inhibitory cardiac sensory receptors in several clinical states including 1) bradycardia, hypotension and gastrointestinal disorders with inferoposterior myocardial ischemia and infarction, 2) bradycardia and hypotension during coronary arteriography, 3) exertional syncope in aortic stenosis, 4) vasovagal syncope, 5) neurohumoral excitation in chronic heart failure, and 6) the therapeutic effects of digitalis.

This article has been cited by other articles:

				W. N. Evans, R. Acherman, K. Kip, and H. Restrepo Hair-Grooming Syncope in Children Clinical Pediatrics, October 1, 2009; 48(8): 834 - 836. [Abstract] [PDF]

				G. Gratze, H. Mayer, and F. Skrabal Sympathetic reserve, serum potassium, and orthostatic intolerance after endurance exercise and implications for neurocardiogenic syncope Eur. Heart J., June 2, 2008; 29(12): 1531 - 1541. [Abstract] [Full Text] [PDF]

				G Roggla, B Moser, and M Roggla Suspension trauma Emerg. Med. J., January 1, 2008; 25(1): 59 - 59. [Full Text] [PDF]

				L. M. Salo, R. L. Woods, C. R. Anderson, and R. M. McAllen Nonuniformity in the von Bezold-Jarisch reflex Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R714 - R720. [Abstract] [Full Text] [PDF]

				A. Woywodt, G. Schneider, H. Haller, and M. Hiss A hopeless case? Nephrol. Dial. Transplant., April 1, 2007; 22(4): 1253 - 1256. [Full Text] [PDF]

				S. P. Patsilinakos, D. G. Antonatos, S. Spanodimos, N. I. Nikolaou, K. Sotirellos, P. I. Korkonikitas, and D. Tsingas Swallow Syncope in a Patient With Esophageal Stenosis Caused by an Ascending Aorta Aneurysm: Differential Diagnosis From Postprandial Hypotension: A Case Report Angiology, February 1, 2007; 58(1): 126 - 129. [Abstract] [PDF]

				P. J. Gheeraert, M. L. De Buyzere, Y. M. Taeymans, T. C. Gillebert, J. P.S. Henriques, G. De Backer, and D. De Bacquer Risk factors for primary ventricular fibrillation during acute myocardial infarction: a systematic review and meta-analysis Eur. Heart J., November 1, 2006; 27(21): 2499 - 2510. [Abstract] [Full Text] [PDF]

				K. P. Savonen, T. A. Lakka, J. A. Laukkanen, P. M. Halonen, T. H. Rauramaa, J. T. Salonen, and R. Rauramaa Heart rate response during exercise test and cardiovascular mortality in middle-aged men Eur. Heart J., March 1, 2006; 27(5): 582 - 588. [Abstract] [Full Text] [PDF]

				T Kawasaki, A Azuma, T Kuribayashi, T Taniguchi, S Asada, T Kamitani, S Kawasaki, H Matsubara, and H Sugihara Enhanced vagal modulation and exercise induced ischaemia of the inferoposterior myocardium Heart, March 1, 2006; 92(3): 325 - 330. [Abstract] [Full Text] [PDF]

				S. Saravanan, M. Kocarev, R. C. Wilson, E. Watkins, M. O. Columb, and G. Lyons Equivalent dose of ephedrine and phenylephrine in the prevention of post-spinal hypotension in Caesarean section Br. J. Anaesth., January 1, 2006; 96(1): 95 - 99. [Abstract] [Full Text] [PDF]

				S. M. Barman, S. W. Phillips, and G. L. Gebber Medullary lateral tegmental field mediates the cardiovascular but not respiratory component of the Bezold-Jarisch reflex in the cat Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1693 - R1702. [Abstract] [Full Text] [PDF]

				C. Fantoni, S. Raffa, F. Regoli, F. Giraldi, M. T. La Rovere, J. Prentice, F. Pastori, S. Fratini, J. A. Salerno-Uriarte, H. U. Klein, et al. Cardiac Resynchronization Therapy Improves Heart Rate Profile and Heart Rate Variability of Patients With Moderate to Severe Heart Failure J. Am. Coll. Cardiol., November 15, 2005; 46(10): 1875 - 1882. [Abstract] [Full Text] [PDF]

				A. Chockalingam, G. Gnanavelu, T. Subramaniam, S. Dorairajan, and V. Chockalingam Right Ventricular Myocardial Infarction: Presentation and Acute Outcomes Angiology, July 1, 2005; 56(4): 371 - 376. [Abstract] [PDF]

				N. Tahara, H. Takaki, A. Taguchi, K. Suyama, T. Kurita, W. Shimizu, S. Miyazaki, T. Kawada, and K. Sunagawa Pronounced HR variability after exercise in inferior ischemia: evidence that the cardioinhibitory vagal reflex is invoked by exercise-induced inferior ischemia Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1179 - H1185. [Abstract] [Full Text] [PDF]

				R. C. Ziegelstein Near-Syncope After Exercise JAMA, September 8, 2004; 292(10): 1221 - 1226. [Abstract] [Full Text] [PDF]

				G Whyte, N Stephens, R Budgett, S Sharma, R E Shave, and W J McKenna Exercise induced neurally mediated syncope in an elite rower: a treatment dilemma Br. J. Sports Med., February 1, 2004; 38(1): 84 - 85. [Full Text] [PDF]

				K. Kashihara, T. Kawada, Y. Yanagiya, K. Uemura, M. Inagaki, H. Takaki, M. Sugimachi, and K. Sunagawa Bezold-Jarisch reflex attenuates dynamic gain of baroreflex neural arc Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H833 - H840. [Abstract] [Full Text] [PDF]

				M. Bechir, C. Binggeli, R. Corti, R. Chenevard, L. Spieker, F. Ruschitzka, T. F. Luscher, and G. Noll Dysfunctional Baroreflex Regulation of Sympathetic Nerve Activity in Patients With Vasovagal Syncope Circulation, April 1, 2003; 107(12): 1620 - 1625. [Abstract] [Full Text] [PDF]

				K. E. Scrogin 5-HT1A receptor agonist 8-OH-DPAT acts in the hindbrain to reverse the sympatholytic response to severe hemorrhage Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2003; 284(3): R782 - R791. [Abstract] [Full Text] [PDF]

				C. J. Thomas and R. L. Woods Guanylyl Cyclase Receptors Mediate Cardiopulmonary Vagal Reflex Actions of ANP Hypertension, February 1, 2003; 41(2): 279 - 285. [Abstract] [Full Text] [PDF]

				J. Lorita, N. Escalona, S. Faraudo, M. Soley, and I. Ramirez Effects of epidermal growth factor on epinephrine-stimulated heart function in rodents Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1887 - H1895. [Abstract] [Full Text] [PDF]

				J. A. Goldstein Pathophysiology and management of right heart ischemia J. Am. Coll. Cardiol., September 4, 2002; 40(5): 841 - 853. [Abstract] [Full Text] [PDF]

				M A Mercader, P J Varghese, S J Potolicchio, G K Venkatraman, and S W Lee New insights into the mechanism of neurally mediated syncope Heart, September 1, 2002; 88(3): 217 - 221. [Abstract] [Full Text] [PDF]

				P. Linz and R. Veelken Serotonin 5-HT3 receptors on mechanosensitive neurons with cardiac afferents Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1828 - H1835. [Abstract] [Full Text] [PDF]

				L. A. Henderson, P. L. Yu, R. C. Frysinger, J.-P. Galons, R. Bandler, and R. M. Harper Neural responses to intravenous serotonin revealed by functional magnetic resonance imaging J Appl Physiol, January 1, 2002; 92(1): 331 - 342. [Abstract] [Full Text] [PDF]

				S. M. Kinsella and J. P. Tuckey Perioperative bradycardia and asystole: relationship to vasovagal syncope and the Bezold-Jarisch reflex Br. J. Anaesth., June 1, 2001; 86(6): 859 - 868. [Abstract] [Full Text] [PDF]

				L.A Graham, J.C Gray, and R.A Kenny Comparison of provocative tests for unexplained syncope: isoprenaline and glyceryl trinitrate for diagnosing vasovagal syncope Eur. Heart J., March 2, 2001; 22(6): 497 - 503. [Abstract] [PDF]

				J. S. Sra Can we assess the efficacy of therapy in neurocardiogenic syncope? J. Am. Coll. Cardiol., February 1, 2001; 37(2): 560 - 561. [Full Text] [PDF]

				C. J. Thomas, C. N. May, A. D. Sharma, and R. L. Woods ANP, BNP, and CNP enhance bradycardic responses to cardiopulmonary chemoreceptor activation in conscious sheep Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2001; 280(1): R282 - R288. [Abstract] [Full Text] [PDF]

				R. Mosqueda-Garcia, R. Furlan, J. T. MD, and R. Fernandez-Violante The Elusive Pathophysiology of Neurally Mediated Syncope Circulation, December 5, 2000; 102(23): 2898 - 2906. [Full Text] [PDF]

				J. Vitovec, J. Spinar, and Czech and Slovak Investigator Group First-dose hypotension after angiotensin-converting enzyme (ACE) inhibitors in chronic heart failure: a comparison of enalapril and perindopril Eur J Heart Fail, September 1, 2000; 2(3): 299 - 304. [Abstract] [Full Text] [PDF]

				J. E. Liu, R. T. Hahn, K. M. Stein, S. M. Markowitz, P. M. Okin, R. B. Devereux, and B. B. Lerman Left Ventricular Geometry and Function Preceding Neurally Mediated Syncope Circulation, February 22, 2000; 101(7): 777 - 783. [Abstract] [Full Text] [PDF]

				A Zaidi, D Benitez, P A Gaydecki, A Vohra, and A P Fitzpatrick Haemodynamic effects of increasing angle of head up tilt Heart, February 1, 2000; 83(2): 181 - 184. [Abstract] [Full Text]

				P. J. Gheeraert, J. P. S. Henriques, M. L. De Buyzere, J. Voet, P. Calle, Y. Taeymans, and F. Zijlstra Out-of-hospital ventricular fibrillation in patients with acute myocardial infarction: Coronary angiographic determinants J. Am. Coll. Cardiol., January 1, 2000; 35(1): 144 - 150. [Abstract] [Full Text] [PDF]

				F. Duru, U. Bauersfeld, and R. Candinas Autonomic effects of radiofrequency catheter ablation Europace, January 1, 2000; 2(2): 181 - 185. [Abstract] [PDF]

				S.W. Parry and R.A. Kenny Tilt table testing in the diagnosis of unexplained syncope QJM, November 1, 1999; 92(11): 623 - 629. [Full Text] [PDF]

				K.-C. Hung, F.-C. Lin, M.-S. Chern, H.-J. Chang, I.-C. Hsieh, and D. Wu Mechanisms and clinical significance of transient atrioventricular block during dobutamine stress echocardiography J. Am. Coll. Cardiol., October 1, 1999; 34(4): 998 - 1004. [Abstract] [Full Text] [PDF]

				J. K. Shoemaker, C. S. Hogeman, and L. I. Sinoway Contributions of MSNA and stroke volume to orthostatic intolerance following bed rest Am J Physiol Regulatory Integrative Comp Physiol, October 1, 1999; 277(4): R1084 - R1090. [Abstract] [Full Text] [PDF]

				C Kouakam, D Lacroix, N Zghal, R Logier, D Klug, P Le Franc, M Jarwe, and S Kacet Inadequate sympathovagal balance in response to orthostatism in patients with unexplained syncope and a positive head up tilt test Heart, September 1, 1999; 82(3): 312 - 318. [Abstract] [Full Text] [PDF]

				T. R. Burklow, J. P. Moak, J. J. Bailey, and F. T. Makhlouf Neurally mediated cardiac syncope: autonomic modulation after normal saline infusion J. Am. Coll. Cardiol., June 1, 1999; 33(7): 2059 - 2066. [Abstract] [Full Text] [PDF]

				E. Di Girolamo, C. Di Iorio, P. Sabatini, L. Leonzio, C. Barbone, and A. Barsotti Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double-blind, placebo-controlled study J. Am. Coll. Cardiol., April 1, 1999; 33(5): 1227 - 1230. [Abstract] [Full Text] [PDF]

				A Elhendy, R T van Domburg, J J Bax, P R Nierop, M L Geleijnse, M M Ibrahim, and J R T C Roelandt The functional significance of chronotropic incompetence during dobutamine stress test Heart, April 1, 1999; 81(4): 398 - 403. [Abstract] [Full Text]

				A. Raviele, M. Brignole, R. Sutton, P. Alboni, P. Giani, C. Menozzi, and A. Moya Effect of Etilefrine in Preventing Syncopal Recurrence in Patients With Vasovagal Syncope : A Double-Blind, Randomized, Placebo-Controlled Trial Circulation, March 23, 1999; 99(11): 1452 - 1457. [Abstract] [Full Text] [PDF]

				S. Mittal, K. M. Stein, S. M. Markowitz, D. J. Slotwiner, S. Rohatgi, and B. B. Lerman Induction of Neurally Mediated Syncope With Adenosine Circulation, March 16, 1999; 99(10): 1318 - 1324. [Abstract] [Full Text] [PDF]

				F. Ammirati, F. Colivicchi, G. Di Battista, F. F. Garelli, and M. Santini Electroencephalographic Correlates of Vasovagal Syncope Induced by Head-Up Tilt Testing Stroke, November 1, 1998; 29(11): 2347 - 2351. [Abstract] [Full Text] [PDF]

				K PRASAD and M P FRENNEAUX Sudden death in hypertrophic cardiomyopathy: potential importance of altered autonomic control of vasculature Heart, June 1, 1998; 79(6): 538 - 540. [Full Text]

				R. D. Deliva and U. Ackermann Atrial natriuretic peptide and mechanisms of cardiovascular control. Role of serotonergic receptors Am J Physiol Regulatory Integrative Comp Physiol, March 1, 1998; 274(3): R711 - R717. [Abstract] [Full Text] [PDF]

				A. K. Younoszai, W. H. Franklin, D. P. Chan, S. C. Cassidy, and H. D. Allen Oral Fluid Therapy: A Promising Treatment for Vasodepressor Syncope Arch Pediatr Adolesc Med, February 1, 1998; 152(2): 165 - 168. [Abstract] [Full Text] [PDF]

				J. J. Atherton, H. L. Thomson, T. D. Moore, K. N. Wright, G. W. F. Muehle, L. E. Fitzpatrick, and M. P. Frenneaux Diastolic Ventricular Interaction : A Possible Mechanism for Abnormal Vascular Responses During Volume Unloading in Heart Failure Circulation, December 16, 1997; 96(12): 4273 - 4279. [Abstract] [Full Text]

				L. A. Lipsitz, R. Morin, M. Gagnon, D. Kiely, and A. Medina Vasomotor instability preceding tilt-induced syncope: does respiration play a role? J Appl Physiol, August 1, 1997; 83(2): 383 - 390. [Abstract] [Full Text] [PDF]

				Z. Mallat, E. Vicaut, A. Sangare, J. Verschueren, G. Fontaine, and R. Frank Prediction of Head-Up Tilt Test Result by Analysis of Early Heart Rate Variations Circulation, July 15, 1997; 96(2): 581 - 584. [Abstract] [Full Text]

				A. Medina, N. Bodick, A. L. Goldberger, M. M. Mahon, and L. A. Lipsitz Effects of Central Muscarinic-1 Receptor Stimulation on Blood Pressure Regulation Hypertension, March 1, 1997; 29(3): 828 - 834. [Abstract] [Full Text]

				A. Englund, M. Fredrikson, and M.°r. Rosenqvist Head-up Tilt Test: A Nonspecific Method of Evaluating Patients With Bifascicular Block Circulation, February 18, 1997; 95(4): 951 - 954. [Abstract] [Full Text]

				M. H. Ellestad Chronotropic Incompetence : The Implications of Heart Rate Response to Exercise (Compensatory Parasympathetic Hyperactivity?) Circulation, April 15, 1996; 93(8): 1485 - 1487. [Full Text]

				J. M. Stewart, M. H. Gewitz, P. K. Woolf, F. Niguidula, B. G. Fish, and G. A. Zeballos ELEVATED ARGININE VASOPRESSIN AND LOWERED ATRIAL NATRIURETIC FACTOR ASSOCIATED WITH HYPERTENSION IN COARCTATION OF THE AORTA J. Thorac. Cardiovasc. Surg., October 1, 1995; 110(4): 900 - 908. [Abstract] [Full Text]

				J. A. Arrowood, E. Goudreau, A. J. Minisi, A. B. Davis, and P. K. Mohanty Evidence Against Reinnervation of Cardiac Vagal Afferents After Human Orthotopic Cardiac Transplantation Circulation, August 1, 1995; 92(3): 402 - 408. [Abstract] [Full Text]

				A. Natale, M. Akhtar, M. Jazayeri, A. Dhala, Z. Blanck, S. Deshpande, A. Krebs, and J. S. Sra Provocation of Hypotension During Head-Up Tilt Testing in Subjects With No History of Syncope or Presyncope Circulation, July 1, 1995; 92(1): 54 - 58. [Abstract] [Full Text]

				W. N. Kapoor Evaluation and Management of the Patient With Syncope JAMA, November 11, 1992; 268(18): 2553 - 2560. [Abstract] [PDF]

				B. P. Grubb, G. Gerard, K. Roush, P. Temesy-Armos, L. Elliott, H. Hahn, and C. Spann Differentiation of Convulsive Syncope and Epilepsy with Head-Up Tilt Testing Ann Intern Med, December 1, 1991; 115(11): 871 - 876. [Abstract] [PDF]

				A. S. Manolis, M. Linzer, D. Salem, and N. A. M. Estes III Syncope: Current Diagnostic Evaluation and Management Ann Intern Med, June 1, 1990; 112(11): 850 - 863. [Abstract] [PDF]

				L. A. Lipsitz, E. R. Marks, J. Koestner, P. V. Jonsson, and J. Y. Wei Reduced Susceptibility to Syncope During Postural Tilt in Old Age: Is Beta-blockade Protective? Arch Intern Med, December 1, 1989; 149(12): 2709 - 2712. [Abstract] [PDF]