The routine use of head-up tilt testing for the evaluation of recurrent unexplained syncope has indicated that the vasodepressor (vasovagal, neurocardiogenic) response may be responsible in up to 50% of cases of recurrent unexplained syncope.<sup>6 Abi-Samra F., Malony J.D., Fouad-Tarazi F.M. , e al. The usefulness of head-up tilt testing and hemodynamic investigations in the work-up of syncope of unknown origin PACE 1988 ;  11 : 1202  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 14 Benditt D.G., Ferguson D.W., Grubb B.P. , e al. Tilt table testing for assessing syncope J Am Coll Cardiol 1996 ;  28 : 263  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 55 Grubb B.P., Kosinski D. Current trends in etiology, diagnosis, and management of neurocardiogenic syncope Curr Opin Cardiol 1996 ;  11 : 32  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 70 Kapoor W.N., Smith M.A., Miller N.L. Upright tilt testing in evaluating syncope: A comprehensive literature review Am J Med 1994 ;  97 : 78  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 73 Kaufmann H. Neurally mediated syncope: Pathogenesis, diagnosis and treatment Neurology 1995 ;  45 : S12

Cliccare qui per andare alla sezione Riferimenti, 144 Samoil D., Grubb B.P. Vasovagal (neurally mediated) syncope: Pathophysiology, diagnosis and therapeutic approach Eur J Cardiac Pacing Electrophysiol 1992 ;  4 : 234

Cliccare qui per andare alla sezione Riferimenti</sup> The vasodepressor response may be triggered by a myriad of stimuli, including orthostatic stress (head-up tilt, lower body negative pressure), emotional stress, relative or absolute blood loss, and severe pain. Similarly, data suggest that other clinical syndromes, such as carotid sinus hypersensitivity or micturition syncope, share a common reflex pathway with the classic vasodepressor response (Figure 1).<sup>73 Kaufmann H. Neurally mediated syncope: Pathogenesis, diagnosis and treatment Neurology 1995 ;  45 : S12

Cliccare qui per andare alla sezione Riferimenti, 78 Kosinski D., Grubb B.P., Temesey-Armos P. Pathophysiologic aspects of neurocardiogenic syncope: Current concepts and new perspectives PACE 1995 ;  18 : 716  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 106 Morillo C.A., Wood M.A., Gilligan D.M. , e al. Diagnostic utility of mechanical, pharmacological and orthostatic stimulation of the carotid sinus in patients with unexplained syncope [abstr] J Am Coll Cardiol 1996 ;  27 : 207A  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 177 Sra J.S., Jazayeri M.R., Dhala A. , e al. Neurocardiogenic syncope: Diagnosis, mechanisms, and treatment Cardiol Clin 1993 ;  11 : 183

Cliccare qui per andare alla sezione Riferimenti, 180 Sutton R., Petersen M.E.V. The clinical spectrum of neurocardiogenic syncope J Cardiovasc Electrophysiol 1995 ;  6 : 569  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> Interest in elucidating the mechanisms responsible for the control of arterial blood pressure have intrigued physiologists and physicians for more than a century. Hunter (1728–1729) may have inadvertently reported the first description of a vasodepressor response when he wrote: “I bled a lady but she fainted and while she continued in the fit the color of the blood that came from the vein was a fine scarlet. The circulation was very languid.”<sup>123 Palmer JF: Works of John Hunter. London, 1837.

Cliccare qui per andare alla sezione Riferimenti</sup> It has been speculated that Hunter noticed the effects of vasodilatation during syncope.<sup>207 Weissler A.M., Warren J.V. Vasodepressor syncope Am Heart J 1959 ;  40 : 786  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> By the late nineteenth century, Hill<sup>64 Hill L. The influence of the force of gravity on the circulation of the blood J Physiol (Lond) 1895 ;  18 : 15

Cliccare qui per andare alla sezione Riferimenti</sup> suggested that emotional syncope results from withdrawal of vasomotor neural traffic. This view was further supported in 1932 by Lewis,<sup>84 Lewis T. Vasovagal syncope and the carotid sinus mechanism with comments on Gower's and Nothangel's syndrome BMJ 1932 ;  1 : 873  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> who introduced the term vasovagal suggesting that both vasodilatation and bradycardia were involved in the vasodepressor response. Lewis demonstrated that bradycardia was vagally mediated; however, despite prevention of bradycardia with atropine, hypotension persisted.<sup>84 Lewis T. Vasovagal syncope and the carotid sinus mechanism with comments on Gower's and Nothangel's syndrome BMJ 1932 ;  1 : 873  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> Further interest in the pathophysiology of this syndrome was triggered by the frequent observation of vasodepressor responses in injured soldiers during World War II.<sup>41 Freeman E.N., Shaffer S.A., Schecter S.A. , e al. The effect of total sympathectomy on the occurrence of shock from hemorrhage J Clin Invest 1938 ;  27 : 359

Cliccare qui per andare alla sezione Riferimenti, 51 Grant R.T., Reeve E.B. Clinical observations on air-raid casualties BMJ 1941 ;  2 : 293

Cliccare qui per andare alla sezione Riferimenti, 52 Grant R.T., Reeve E.B. Clinical observations on air-raid casualties BMJ 1941 ;  2 : 329

Cliccare qui per andare alla sezione Riferimenti, 99 McMichael J. Clinical aspects of shock JAMA 1944 ;  124 : 275

Cliccare qui per andare alla sezione Riferimenti, 165 Shenkin H.A., Cheney R.H., Govons S.R. , e al. On the diagnosis of hemorrhage in man: A study of volunteers bled large amounts Am J Med Sci 1944 ;  208 : 421  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> This interest was renewed in the 1960s by the advent of aerospace medicine in an attempt to understand the physiology of G force–induced vasodepressor syncope.<sup>42 Gauer O.H., Henry J.P. Negative (−Gz) acceleration in relation to arterial oxygen saturation, subendocardial hemorrhage and venous pressure in the forehead Aerosp Med 1964 ;  35 : 533

Cliccare qui per andare alla sezione Riferimenti, 43 Gauer O.H., Thron H.L. Postural changes in the circulation Handbook of Physiology, Section 2: Circulation Washington, DC: American Physiological Society (1965).  2409

Cliccare qui per andare alla sezione Riferimenti, 195 Vogt F.B. Tilt table and plasma volume changes with short term deconditioning experiments Aerosp Med 1967 ;  39 : 564

Cliccare qui per andare alla sezione Riferimenti</sup> The introduction of head-up tilt as a clinical diagnostic tool in 1986 by Kenny and associates<sup>77 Kenny R.A., Ingram A., Bayliss J. , e al. Head-up tilt: A useful test for investigating unexplained syncope Lancet 1986 ;  1 : 1352

Cliccare qui per andare alla sezione Riferimenti</sup> revived the interest in elucidating the mechanism of vasodepressor syncope.<sup>78 Kosinski D., Grubb B.P., Temesey-Armos P. Pathophysiologic aspects of neurocardiogenic syncope: Current concepts and new perspectives PACE 1995 ;  18 : 716  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 131 Rea R.F. Neurally mediated hypotension and bradycardia: Which nerves? How mediated? J Am Coll Cardiol 1989 ;  14 : 1633  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 133 Rea R.F., Thames M.D. Neural control mechanisms and vasovagal syncope J Cardiovasc Electrophysiol 1993 ;  4 : 587  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 176 Sra J.S., Akhtar M. Cardiac pacing during neurocardiogenic (vasovagal) syncope J Cardiovasc Electrophysiol 1995 ;  6 : 751  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup>

Activation of left ventricular vagal–C mechanoreceptors owing to a sympathetically mediated increase in contractility in an empty or preload reduced left ventricular cavity leading to a reflex increase in vagal efferent traffic and sympathetic withdrawal to skeletal muscle arterioles and splanchnic venules has been usually regarded as the potential mechanism of vasodepressor syncope (Figure 2).<sup>12 Bearn A.G., Billing B., Edholm O.G. , e al. Hepatic flow and carbohydrate changes in man during fainting J Physiol (Lond) 1951 ;  115 : 442

Cliccare qui per andare alla sezione Riferimenti, 69 Jarisch A., Zotterman Y. Depressor reflexes from the heart Acta Physiol Scand 1948 ;  16 : 31

Cliccare qui per andare alla sezione Riferimenti, 95 Mark A.L. The Bezold-Jarisch reflex revisited: Clinical implications of inhibitory reflexes originating in the heart J Am Coll Cardiol 1983 ;  1 : 90  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 199 Wallin B.G., Sundlof G. Sympathetic outflow to muscles during vasovagal syncope J Auton Nerv Syst 1982 ;  6 : 287

Cliccare qui per andare alla sezione Riferimenti</sup> This view, largely supported by experimental evidence obtained from cats by Öberg<sup>118 Öberg B., Thore´n P. Studies on left ventricle receptors, signalling in non-medullated vagal afferents Acta Physiol Scand 1972 ;  85 : 145

Cliccare qui per andare alla sezione Riferimenti, 119 Öberg B., Thore´n P. Increased activity in left ventricular receptors during hemorrhage or occlusion of caval veins in the cat: A possible cause of the vasovagal reaction Acta Physiol Scand 1972 ;  85 : 164

Cliccare qui per andare alla sezione Riferimenti, 120 Öberg B., White S. Circulatory effects of interruption and stimulation of cardiac vagal afferents Acta Physiol Scand 1970 ;  80 : 383

Cliccare qui per andare alla sezione Riferimenti, 121 Öberg B., White S. The role of vagal cardiac nerves and arterial baroreceptors in the circulatory adjustments to hemorrhage in the cat Acta Physiol Scand 1970 ;  80 : 395

Cliccare qui per andare alla sezione Riferimenti</sup> and Thore´n<sup>186 Thore´n P. Role of cardiac C fibers in cardiovascular control Rev Physiol Biochem Pharmacol 1979 ;  86 : 1

Cliccare qui per andare alla sezione Riferimenti, 187 Thore´n P., Donald D.E., Shepherd J.T. Role of heart and lung receptors with nonmedullated vagal afferents in circulatory control Circ Res 1976 ;  38 : II-I2

Cliccare qui per andare alla sezione Riferimenti</sup> and rats in the mid 1970s prevailed until the observation of vasodepressor syncope in heart transplant recipients reported by several groups.<sup>38 Fitzpatrick A.P., Banner N., Cheng A. , e al. Vasovagal syncope may occur after orthotopic heart transplantation J Am Coll Cardiol 1993 ;  21 : 1132  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 86 Lightfoot J.T., Rowe S.A., Fortney S.M. Occurrence of presyncope in subjects without ventricular innervation Clin Sci 1993 ;  85 : 695

Cliccare qui per andare alla sezione Riferimenti, 142 Rudas L., Pflugfelder P.W., Kostuk W.J. Vasodepressor syncope in a cardiac transplant recipient: A case of vagal reinnervation? Can J Cardiol 1992 ;  8 : 403

Cliccare qui per andare alla sezione Riferimenti, 204 Waxman M.B., Cameron D.A., Wald R.W. Role of ventricular vagal afferents in the vasovagal reactions J Am Coll Cardiol 1993 ;  21 : 1138  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> Species differences in the genesis of the vasodepressor response may be responsible for this discrepancy.<sup>164 Shen Y.T., Knight D.R., Thomas J.X. , e al. Relative roles of cardiac receptors and arterial baroreceptors during hemorrhage in conscious dogs Circ Res 1990 ;  66 : 397

Cliccare qui per andare alla sezione Riferimenti</sup> Morita and Vatner<sup>109 Morita H., Vatner S.F. Effects of hemorrhage on renal nerve activity in conscious dogs Circ Res 1985 ;  57 : 788

Cliccare qui per andare alla sezione Riferimenti</sup> observed in conscious dogs sympathoexcitation and tachycardia as the initial response to hemorrhage. Progressive hemorrhage led to sympathetic withdrawal and bradycardia. Interruption of cardiac afferents or arterial baroreceptors, however, was unable to prevent the onset of the vasodepressor response.<sup>109 Morita H., Vatner S.F. Effects of hemorrhage on renal nerve activity in conscious dogs Circ Res 1985 ;  57 : 788

Cliccare qui per andare alla sezione Riferimenti</sup> These findings suggest that cardiac afferents may not be required to trigger the vasodepressor response and have been met with the proposal of alternative hypotheses. This article focuses on the current knowledge regarding the neuroendocrine, hemodynamic, and neurophysiologic components of the vasodepressor response and proposes a unifying hypothesis for vasodepressor syncope.