(Circulation. 1997;95:395-400.)
© 1997 American Heart Association, Inc.
Articles |
Baroreflex Sensitivity in Patients With Vasovagal Syncope
the Heart Failure Research Unit, Department of Medicine, University of Queensland, Royal Brisbane Hospital, Brisbane, Australia.
Correspondence to Prof Michael Frenneaux, Cardiology Department, University of Wales, College of Medicine, Heath Park, Cardiff, Wales LF4 4XN, UK.
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Abstract |
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Background In the present study, we tested the hypothesis that baroreflex sensitivity is reduced in patients with vasovagal syncope compared with normal control subjects.
Methods and Results We investigated 30 patients with vasovagal syncope (mean age, 43.6±16.7 years; 14 men and 16 women) and 32 normal control subjects (mean age, 41.8±17.0 years; 24 men and 8 women). Cardiopulmonary baroreceptor sensitivity was assessed by measuring the change in forearm vascular resistance during subhypotensive lower body negative pressure (LBNP). Carotid baroreflex sensitivity was assessed by measuring the change in RR interval during the manipulation of carotid transmural pressure. Phenylephrine baroreceptor sensitivity was assessed on the basis of the linear regression slope of the RR interval versus systolic arterial blood pressure during the increment in blood pressure after intravenous administration of phenylephrine. In patients with vasovagal syncope, during the application of -10 mm Hg LBNP, forearm vascular resistance decreased by 0.7±11.6 U versus an increase of 8.3±6.2 U in control subjects (P=.002). Phenylephrine baroreceptor sensitivity was 11±7 ms/mm Hg in patients versus 14±6 ms/mm Hg in control subjects (P=NS). Carotid baroreflex sensitivity was 4±6 versus 4±2 ms/mm Hg in patients and control subjects, respectively (P=NS).
Conclusions In patients with vasovagal syncope, during the application of subhypotensive LBNP, there is impaired forearm vasoconstriction or paradoxical forearm vasodilation. This suggests impaired cardiopulmonary baroreceptor inactivation or paradoxical activation of these receptors and is consistent with reduced cardiopulmonary baroreceptor sensitivity.
Key Words: baroreceptors • syncope • vasodilation
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Introduction |
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Blood pressure and heart rate are normally controlled by complex factors, including input from baroreceptors within the carotid sinus and aortic arch (the "high-pressure baroreceptors") and within the atria, great veins, and ventricles (the "low-pressure baroreceptors"). In the resting physiological state, some of the low-pressure baroreceptors are silent, but others fire spontaneously at a low rate of
1 s-1.1 2 3 There is evidence that the high-pressure baroreceptors exhibit pulse synchronous firing within the physiological resting blood pressure range.4 An increase in blood pressure increases the firing rate of the high-pressure baroreceptors.4 This results in a decrease in heart rate and systemic vascular resistance, with a consequent decrease in blood pressure.5 Volume or pressure loading of the heart increases the firing rate of the low-pressure baroreceptors, with the same effect.6 7 Central blood volume unloading that is insufficient to decrease blood pressure decreases the firing rate of low-pressure baroreceptors (ie, inactivates them), resulting in an increase in systemic vascular resistance.8 As central volume unloading becomes greater, and particularly as blood pressure starts to fall, inactivation of high-pressure baroreceptors also occurs.9 Profound central volume unloading associated with marked hypovolemia may for reasons that are unclear result in paradoxical activation of low-pressure baroreceptors; this has been proposed as a model of the vasovagal response.10 However, evidence for the role of cardiopulmonary mechanoreceptor abnormalities in patients with vasovagal syncope remains unclear. First, recent data call into question whether this is the exclusive mechanism.11 12 Dickinson13 proposed that activation of other cardiopulmonary (ie, nonventricular) mechanoreceptors may be an important mechanism. Second, a recent study reported exaggerated forearm vasoconstriction during the application of subhypotensive lower body negative pressure (LBNP) in patients with vasovagal syncope consistent with augmented cardiopulmonary baroreceptor sensitivity (ie, enhanced inactivation of cardiopulmonary mechanoreceptors).14 However, another study by the same authors15 demonstrated markedly impaired forearm vasoconstriction in patients with vasovagal syncope as early as 2 minutes into tilt testing (long before the onset of overt vasovagal features). This implies reduced cardiopulmonary baroreceptor sensitivity (ie, a failure of the inactivation of the cardiopulmonary mechanoreceptors, which would normally be expected to occur with central volume unloading).
To clarify the role of abnormalities of cardiopulmonary or arterial baroreceptor function in patients with vasovagal syncope, we assessed cardiopulmonary, phenylephrine baroreceptor, and carotid baroreflex sensitivities, testing the hypothesis that baroreflex sensitivity is decreased in patients with vasovagal syncope. To confirm the integrity of the central and efferent component of the reflex arc, we also assessed the pressor responses to 
1-adrenergic stimulation and to handgrip. We hypothesized that the abnormality would most likely be in the afferent limb of the cardiopulmonary baroreflex.
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Methods |
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Patients
Of 74 patients referred to the Syncope Clinic of the Royal Brisbane Hospital for assessment of syncope between January 1993 and December 1994, a diagnosis of vasovagal syncope was established in 39 patients on the basis of a typical history; negative electroencephalographic, echocardiographic, and cardiac electrophysiological (where appropriate) studies; and a positive head-up tilt test without isoproterenol (60° head-up tilt for 45 minutes).16 None of the patients had a history suggestive of ischemic heart disease; none were hypertensive; all had negative exercise ECGs for ischemia; and all were in sinus rhythm. Patients were excluded on the basis of a definite history or clinical suspicion of autonomic failure (specifically, none had diabetes mellitus or renal impairment). Of this group, 30 consented to enter the study. Thirty-two approximately age-matched normal subjects with no previous cardiac history or current symptoms, normal cardiovascular and neurological examinations, normal ECG and echocardiogram, and negative tilt tests were recruited from the gastroenterology department endoscopy database and enrolled as control subjects. Three of the patients had been taking vasoactive medications (1 patient each received 100 mg of disopyramide BID, 80 mg of sotalol BID, and 50 mg of metoprolol BID). None of the control subjects had been taking vasoactive medications.
Study Protocol
The investigations were performed at the Royal Brisbane Hospital with the approval of the hospital ethics committee. Informed consent was obtained for all patients and control subjects. Subjects arrived at 8 AM after fasting since midnight. All cardioactive medications were withdrawn for at least five half-lives before the study.
Phenylephrine Baroreceptor Sensitivity
Phenylephrine baroreceptor sensitivity was assessed using a standard phenylephrine ramp method.5 In brief, phenylephrine was injected into an antecubital vein at a dose sufficient to progressively increase systolic blood pressure by 20 to 30 mm Hg and therefore increase the activity of the arterial baroreceptors. This induced a linearly related lengthening in RR interval, which allowed the slope of the linear regression of the RR interval over systolic blood pressure to be taken as the baroreflex sensitivity during baroreceptor stimulation. Blood pressure was measured with a Finapres recorder (Ohmeda 2300). Blood pressure and ECG data were recorded with the use of the Acq Knowledge data acquisition program (Biopac Systems) on an Apple Macintosh II CI computer.
The phenylephrine dose required to increase the systolic blood pressure by 30 mm Hg was administered three times, and three separate measurements of baroreceptor sensitivity were calculated. The mean value of these three measurements was used to represent phenylephrine baroreceptor sensitivity.
Cardiopulmonary Baroreceptor Sensitivity
Cardiopulmonary receptors were deactivated by reducing central venous pressure through the application with the use of an LBNP device of negative pressures sufficiently mild (-10 and -20 mm Hg) to have little effect on blood pressure (not causing a decrease in mean blood pressure of >10 mm Hg) and thus to modify arterial baroreceptor activity to only a minor degree.8
During this study, arterial blood pressure was measured with a Finapres recorder. The pressure within the lower body box was measured with a transducer (Dwyer series 602 differential pressure transmitter integrated with an Innotech current-sensing controller and display). Forearm blood flow was measured with a standard mercury-in-Silastic strain-gauge plethysmographic technique17 (Hokanson). Forearm blood flow was calculated from three slopes, and the results were averaged. The ECG was recorded. Central venous pressure was recorded using a Baxter transducer (Baxter Health Care Corp) via a central venous line inserted from the antecubital vein. All data were acquired with an Acq Knowledge multichannel data-acquisition system and fed to an Apple Macintosh II CI computer. Measurements were performed at rest and during applications of -10 and -20 mm Hg LBNP after stabilization for 2 minutes at each pressure. Forearm vascular resistance (FVR), expressed in resistance units, was calculated as the quotient of the mean arterial pressure (mm Hg) and forearm blood flow (mL·min-1·100 mL-1).
Carotid Baroreceptor Sensitivity
Carotid arterial baroreceptor sensitivity was measured with the use of a standard technique.18 In brief, the patients were fitted with a lead collar connected to an air source. This permitted the application of negative and positive pressures around the neck, increasing and decreasing carotid transmural pressure and selectively stimulating and inhibiting carotid baroreceptors, respectively. The negative and positive pressures were applied in six random steps ranging from -50 to +50 mm Hg. Each step was of 10-second duration. Blood pressure was again recorded with a Finapres recorder, and the ECG was recorded. All data were acquired with an Acq Knowledge multichannel data-acquisition system and fed to an Apple Macintosh II CI computer. The maximal lengthening or shortening in RR interval observed over three beats after the application of neck pressure represented the reflex response for that applied pressure, and the slope of the linear regression of the RR intervals versus applied neck pressures was taken as the carotid baroreflex sensitivity.
Response to Handgrip and Intravenous Phenylephrine
To assess whether the vasoconstrictor response to -adrenergic stimulation is impaired in patients with vasovagal syncope, we assessed the blood pressure response to the 1-agonist phenylephrine in patients and control subjects according to a previously reported technique.19 In brief, the dose response of phenylephrine was assessed when phenylephrine baroreceptor sensitivity was measured. Phenylephrine was injected into an antecubital vein. Blood pressure was measured with a Finapres recorder (Ohmeda 2300). Blood pressure and ECG data were recorded with the Acq Knowledge data-acquisition program on an Apple Macintosh II CI computer. The dose required to produce an increase in maximum systolic blood pressure of 30 mm Hg was divided by the patient's weight to give a weight-adjusted dose-response ratio.
To assess whether reflex responses to other pressor maneuvers were impaired in patients with vasovagal syncope, the response of diastolic blood pressure to handgrip was assessed in patients and control subjects. Handgrip was maintained at 30% of the maximum voluntary contraction to a maximum of 5 minutes with the use of a handgrip dynamometer, and blood pressure was measured every minute. The difference between the blood pressure value just before the release of handgrip and the value before the start was taken as the measure of response.20
Data Analysis
Results are expressed as mean±SD. Statistical analysis was performed with unpaired t tests. A value of P<.05 was considered statistically significant.
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Results |
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Patient Characteristics
Fourteen of the patients were men and 16 were women, with a mean age of 43.6±16.7 years. The mean age of the control subjects was 41.8±17.0 years; 24 were men, and 8 were women. None of the patients or control subjects participated in competitive athletics. The patients gave a history of 12.0±10.6 syncopal episodes for each, whereas none of the control subjects gave a history of syncope. The tilt tests were classified as cardioinhibitory in 15 and vasodepressive in 15, where a cardioinhibitory response was defined as a decrease in heart rate at the time of syncope to
60 bpm followed by a decrease in blood pressure. A vasodepressor response was defined as a decrease in blood pressure at the time of syncope, where heart rate is maintained at >60 bpm.21
Phenylephrine Baroreceptor Sensitivity
As shown in Table 1
, phenylephrine baroreceptor sensitivity was similar in patients with vasovagal syncope and in control subjects (11±7 versus 14±6 ms/mm Hg, P=.09).
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Cardiopulmonary Baroreceptor Sensitivity
As shown in Table 2, heart rate and mean blood pressure were similar in the patients and the control subjects at baseline and during the application of LBNP. Mean blood pressure decreased in 1 patient by 22 mm Hg at -10 mm Hg LBNP and in another patient by 11 mm Hg at -20 mm Hg LBNP. These data were therefore excluded from the analysis. Change in systolic blood pressure was similar in patients versus control subjects at -10 and -20 mm Hg LBNP (1.6±6.9 versus 1.1±5.3 mm Hg, P=NS, and 0.2±14.8 versus 3.0±8.2 mm Hg, P=NS, respectively). Changes in diastolic blood pressure were also similar in patients versus control subjects at -10 and -20 mm Hg LBNP (4.8±7.7 versus 3.0±8.2 mm Hg, P=NS, and 4.4±13.5 versus 4.0±8.9 mm Hg, P=NS, respectively), as was change in pulse pressure (-3.2±8.5 versus -3.4±9.5 mm Hg, P=NS, and -4.6±9.7 versus -1.2±10.3 mm Hg, P=NS, respectively).
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As shown in Table 1
, FVR decreased by 0.7±11.6 U in patients compared with an increase of 8.3±6.2 U in control subjects (P=.002) during the application of -10 mm Hg LBNP (Figure). In 14 patients, there was a decrease in FVR during the application of -10 mm Hg LBNP, a pattern of response that was not seen in any of the control subjects. The increase in FVR was also less in the patients at -20 mm Hg LBNP compared with the control group (0.4±12.5 versus 12.3±12.2 U, P=.003). The change in FVR was similar in those with cardioinhibitory and those with vasodepressive syncope at both -10 and -20 mm Hg LBNP (0.1±5.4 versus -1.4±15.6 U, P=NS, and -0.6±3.7 versus 1.2±16.4 U, P=NS, respectively). The decrease in central venous pressure was similar in patients and control subjects at -10 mm Hg LBNP (2±2 versus 2±1 mm Hg, P=NS) and at -20 mm Hg LBNP (4±2 versus 3±3 mm Hg, P=NS). The patient group was divided into those with a high number of episodes of syncope (greater than the mean for the group) and those with a low number of episodes (lower than the mean for the group). Those with a low number of episodes of syncope had a greater increase in FVR during the application of -10 mm Hg LBNP than did those with a high number of episodes of syncope in whom FVR decreased (-6.2±11.4 versus 4.8±9.4 U, P=.016).
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Because there was an excess number of women in the patient group versus the control group, subgroup analysis was performed. The increase in FVR was less in the male patients at -10 and -20 mm Hg LBNP than in the male control group (1.6±7.4 versus 7.3±5.6 U, P=.03, and 0.5±13.7 versus 13.6±10.7 U, P=.01, respectively). The increase in FVR was less in the female patients at -20 mm Hg LBNP (-1.7±14.6 versus 20.2±13.4 U, P=.02), but at -10 mm Hg LBNP, the difference did not reach statistical significance (-2.2±14.7 versus 11.8±6.1 U, P=.09).
Carotid Baroreceptor Sensitivity
As shown in Table 1, carotid baroreflex sensitivity was similar in the patients and control subjects (4±6 versus 4±2 ms/mm Hg, respectively, P=NS).
Response to Handgrip and Phenylephrine
The increase in diastolic blood pressure during handgrip was similar in the patients and control subjects (22±9 versus 22±10 mm Hg, P=NS). The phenylephrine dose-response ratio was also similar in the patients and control subjects (3.5±1.9 versus 3.9±2.0 mm Hg·kg-1·mg-1 phenylephrine, P=NS).
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Discussion |
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The important findings of this study are that there is impaired forearm vasoconstriction and in some patients paradoxical vasodilation during the application of subhypotensive LBNP in patients with tilt-table–positive vasovagal syncope compared with age-matched normal control subjects, confirming the hypothesis that patients with vasovagal syncope have decreased cardiopulmonary baroreceptor sensitivity. Carotid baroreceptor sensitivity was similar in patients and control subjects. There was a nonsignificant trend to lower phenylephrine baroreceptor sensitivity in patients. The pressor responses to
1-adrenergic stimulation and to handgrip were normal in patients with vasovagal syncope.
Baroreflex Function in Patients With Vasovagal Syncope
We confirmed our hypothesis that cardiopulmonary baroreceptor sensitivity is reduced in patients with vasovagal syncope. Compared with control subjects, patients with vasovagal syncope demonstrated either reduced forearm vasoconstriction, reflecting less inactivation of cardiopulmonary baroreceptors than in control subjects, or paradoxical forearm vasodilation during LBNP, most likely as a result of paradoxical activation of these receptors. Although these differences are highly significant statistically, the Figure emphasizes the much greater variability of the response in patients versus control subjects, which may be consistent with heterogeneous mechanisms in patients with vasovagal syncope. This heterogeneity does not appear to relate to the pattern of the vasovagal response on tilt-table testing (cardioinhibitory or vasodepressor). Phenylephrine baroreceptor sensitivity assesses predominantly carotid and aortic baroreflex systems,22 although there is some evidence in cats that cardiopulmonary baroreceptors may be involved.23
Cardiopulmonary baroreceptor sensitivity was lower in patients with frequent episodes of syncope than in those with less frequent episodes of syncope, suggesting an association between the degree of abnormality of baroreflex function and disease severity.
In one previous study, phenylephrine baroreceptor sensitivity was lower in patients with vasovagal syncope than in control subjects.24 Our data show a similar trend, although the difference was not significant.
The patients in our study were relatively young. There are important clinical differences in vasovagal syncope in young versus older patients. In the elderly, clear precipitants are often absent, and a prodrome is often lacking (malignant vasovagal syncope). These two syndromes may therefore be very different pathophysiologically. It has been proposed that vasovagal syncope and carotid sinus syndrome may be very similar pathophysiologically. In one series, 50% of patients with carotid sinus syndrome had positive tilt-table tests.25 Carotid and phenylephrine baroreceptor sensitivities are increased in the latter.25 26 Currently, no data are available on baroreceptor sensitivity in older patients with vasovagal syncope.
Cause of Lower Cardiopulmonary Baroreceptor Sensitivity in Patients With Vasovagal Syncope
Lower cardiopulmonary baroreceptor sensitivity in patients with vasovagal syncope could be the result of an intrinsic abnormality of the baroreceptor reflex arc. Alternatively, it could be the result of exaggerated venous pooling, leading to an abnormal decrease in central venous filling pressures and resulting in inappropriate firing of ventricular baroreceptors.27 The latter seems unlikely for two reasons. First, the observation of similar decreases in central venous pressure in patients and control subjects makes exaggerated central hypovolemia in the patients unlikely. Second, we previously investigated changes in forearm venous tone during the application of similar levels of LBNP and demonstrated that patients constrict their veins as much as control subjects.28
The difference in responses of the venous and resistance vessels to central volume unloading implies deferential changes in autonomic outflow in these two beds. The potential role of activation of nitroxidergic nerves as a mechanism of the dilation of resistance vessels may warrant study. Dense innervation of cerebral vessels by nitroxidergic neurons has been demonstrated, but the functional significance is unclear.29 Nitroxidergic innervation of the human corpus cavernosum has been demonstrated and may be important in penile erection.30
We therefore believe our observations are most likely the result of an abnormality of the cardiopulmonary baroreflex arc. We previously reported abnormal forearm resistance vessel vasodilator responses and impaired splenic venoconstriction during dynamic leg exercise in patients with vasovagal syncope, which may be the result of exaggerated cardiopulmonary mechanoreceptor activation on exercise in these patients.19 28 31 Taken together, these observations are consistent with abnormal cardiopulmonary baroreflex responses during both central volume unloading and exercise in patients with vasovagal syncope.
Site of the Abnormality Within the Baroreceptor Reflex Arc in Patients With Vasovagal Syncope
The site of the abnormality of the baroreceptor reflex arc in patients with vasovagal syncope is uncertain, but we believe that our data suggest it is probably within the afferent limb of the reflex arc. We do not believe an impairment of peripheral responsiveness to -adrenergic stimulation is the explanation. First, this would not explain the paradoxical vasodilation during either exercise or LBNP that is observed in some of the patients. Second, the pressor response to phenylephrine was normal in patients with vasovagal syncope. The normal response to handgrip implies that central command and skeletal metaboreceptor reflexes are intact and that central integration (at least of this reflex) and the efferent limb are intact.32 The normal carotid baroreflex sensitivity in patients with vasovagal syncope implies normal carotid baroreflex function and normal central integration, at least of this reflex. Thus, our data support the existence of an abnormality of the afferent limb of the cardiac baroreflex. The site of this abnormality within the afferent limb remains speculative. It might be caused by a primary abnormality of the receptors or abnormal global or local left ventricular wall strains. One group has demonstrated a greater reduction in left ventricular volumes in patients with vasovagal syncope during tilt-table testing than in control subjects.33 Although our observations are consistent with an abnormality in the cardiopulmonary baroreflex arc, this does not exclude the presence of other factors. Emotion and pain commonly precipitate vasovagal syncope, suggesting that central factors may also be important. The observation by Evans et al11 that phase 2 in the rabbit hemorrhage model cannot always be completely blocked by vagotomy also suggests that cardiac vagal afferents are not the only input to the brainstem capable of precipitating the vasovagal reaction. Stimulation of the rostral cingulate gyrus in dogs precipitated vasovagal syncope consistent with the importance of central factors.34 The relative importance of central factors versus an abnormality in the cardiopulmonary baroreflex arc may differ from patient to patient. This may at least in part explain the heterogeneity of responses observed in patients in the present study.
Comparison With Previous Studies
One group has previously demonstrated impaired forearm vasoconstriction in patients with vasovagal syncope at 2 minutes into head-up tilt testing.15 However, the same authors reported an increase in forearm vasoconstriction during LBNP in patients with vasovagal syncope.14 Our results are consistent with the results of the first of these studies but differ from those of the second study.
The question arises as to why the results of these studies differ. The most likely explanation is that patients with vasovagal syncope may be a heterogeneous group with different mechanisms that are operative in different patients. The Figure demonstrates a much greater variability in forearm vascular response to LBNP in patients versus control subjects, presumably reflecting this heterogeneity. There may be some patients in whom there is an increase in forearm vasoconstriction at minor levels of central venous unloading but paradoxical vasodilation with more profound levels of central venous volume unloading. An alternative explanation noted by Sneddon et al14 is that they used patients with unexplained syncope and negative tilt-table tests as the control population, and it is possible that at least some of the control subjects had vasovagal syncope.
Study Limitations
Our control group consisted of subjects with no past history of syncope and a negative tilt test. However, it is likely that all subjects have the potential for vasovagal syncope given sufficiently adverse circumstances. This raises the question of who can be considered to be a control in this disorder. Nevertheless, we believe the use of a population with no history of syncope and a negative tilt test selects a group of patients with a high threshold for vasovagal syncope and represents the most appropriate group of control subjects.
The patients and control subjects were not sex matched. There was a relative excess of men in the control group. However, subgroup analysis confirmed that female patients had lower cardiopulmonary baroreceptor sensitivity than female control subjects and that male patients had lower cardiopulmonary baroreceptor sensitivity than male control subjects. Therefore, we do not believe that this bias is a significant limitation of the study. As discussed earlier, our patient population was relatively young, and our data may not apply to elderly patients with vasovagal syncope, a group in whom clinical features differ from those of younger patients.
Because central venous pressure decreased equally in the vasovagal patients and the control subjects, we conclude that there was no evidence of exaggerated central hypovolemia in patients. However, because pressure is only an indirect reflection of volume, we cannot be certain of volume changes.
Although we demonstrated that the carotid baroreflex sensitivity as assessed by change in RR interval per unit change in applied neck pressure was similar in patients with vasovagal syncope and control subjects, these data cannot be generalized to other aspects of carotid baroreflex control. Specifically, we assessed the carotid/vagal reflex. The carotid/sympathetic reflex (as measured by change in muscle sympathetic nerve activity) was not assessed. These two aspects of the reflex may differ. For example, in the canine rapid pacing heart rate model, one report describes loss of the heart failure responses to pharmacologically induced changes in blood pressure but preservation of arterial baroreflex control of hindlimb vascular resistance.35 Similarly, the phenylephrine baroreceptor sensitivity reported in the present study concerned only the vagal aspect of the efferent limb of the reflex.
Although the phenylephrine technique that we used in the present study to assess baroreceptor sensitivity is the dominant one in the literature, others have plotted heart rate against blood pressure change. This may result in differences in interpretation. In one animal study, exercise resulted in reduction in carotid baroreceptor sensitivity when plotted as RR interval versus blood pressure, whereas there was no change in sensitivity when plotted as heart rate versus blood pressure.36
Conclusions
During the application of LBNP in patients with vasovagal syncope, there is impaired forearm vasoconstriction or paradoxical vasodilation. This implies reduced inactivation or paradoxical activation of cardiopulmonary mechanoreceptors and is contrary to a previous study demonstrating exaggerated forearm vasoconstriction. Taken together with our previous observations of normal reflex forearm venoconstriction during the application of subhypotensive LBNP and evidence of probable profound cardiopulmonary mechanoreceptor activation during exercise as well as during tilt-table testing, we believe that the evidence indicates an abnormality in the afferent limb of the cardiac baroreflex, supporting our initial hypothesis. This may not, however, be the sole abnormality. Emotion commonly precipitates vasovagal syncope, suggesting the importance of central factors.
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Acknowledgments |
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This work was supported in part by grants from the National Health and Medical Research Council of Australia (project grant 665 941193 and scholarship 948220).
Received May 28, 1996; revision received August 21, 1996; accepted September 1, 1996.
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