Background Baroreflexes originate in the great vessels of theneck and thorax and prevent arterial pressure from rising orfalling excessively.
Methods This study was undertaken to clarify the cause, clinicalspectrum, and therapy of this disorder. We studied 11 patientswith baroreflex failure presenting as severe, labile hypertensionand hypotension, often with headache, diaphoresis, and emotionalinstability, and characterized by the failure of exogenous vasoactivesubstances to alter heart rate. Each underwent hemodynamic monitoringand biochemical, physiologic, and pharmacologic testing.
Results The patients' maximal systolic blood pressures rangedfrom 164 to 280 mm Hg, and their minimal systolic pressuresranged from 58 to 96 mm Hg. Plasma norepinephrine and epinephrineconcentrations were sometimes many times normal during blood-pressuresurges. All the patients had excessive pressor and tachycardicresponses to the mental-arithmetic and cold pressor tests andmarked hypersensitivity to clonidine. The underlying causesof baroreflex failure included the familial paraganglioma syndrome,neck surgery or radiation therapy for pharyngeal carcinoma,bilateral lesions of the nucleus tractus solitarii, and surgicalsection of the glossopharyngeal nerves; in two patients thecause was unknown. Therapy with clonidine reduced the frequencyof attacks by 81 percent and attenuated the elevated blood pressureand heart rate in the attacks that occurred.
Conclusions The syndrome of baroreflex failure should be consideredin patients with otherwise unexplained labile hypertension.Clonidine attenuates the pressor and tachycardic surges in baroreflexfailure.
Baroreflexes buffer changes in arterial pressure so that excessivefluctuations of blood pressure are avoided1,2,3,4,5,6,7. Baroreceptorsin each carotid sinus send information about distention of thevessel wall by the glossopharyngeal nerves to the brain stem8.Other baroreceptors in the aortic arch and the great vesselsof the thorax transmit similar information by the vagal nervesto the same brain-stem nuclei9. In addition, the blood volumein the thorax is sensed by low-pressure receptors linked bythe vagal nerves to the brain stem. The brain-stem structuresreceiving this information are the commissural, dorsolateral,and medial portions of nucleus tractus solitarii10,11.
Abnormalities in the vascular baroreceptors, the glossopharyngealor vagal nerves, or the brain stem could all lead to baroreflexfailure. Yet there has been confusion about the clinical presentationof the syndrome, with many authors using the terms "baroreflexfailure" and "autonomic failure" interchangeably. Autonomicfailure is often associated with severe orthostatic hypotensionand reduced sympathetic activity. In contrast, the few patientswith anatomical lesions giving rise to baroreflex failure12,13,14,15,16,17have had little orthostatic hypotension, and their illness isdominated by volatile hypertension.
True baroreflex failure entails the loss of buffering of bloodpressure and is characterized by volatility of the blood pressureand heart rate. To determine the clinical spectrum of the syndromeof baroreflex failure, we prospectively evaluated 11 patientswith unambiguous dysfunction of arterial baroreflexes.
Methods
Among approximately 500 patients referred to the Autonomic DysfunctionCenter at Vanderbilt University because of autonomic or blood-pressureproblems, 11 patients with arterial baroreflex failure wereidentified (Table 1). The reasons for referral included evaluationfor essential hypertension, suspected pheochromocytoma, uncontrolledhypertension, or recognition that the integrity of glossopharyngealor vagal nerves had been compromised. Baroreflex failure wasdocumented by the inability of infusions of pressor and depressordrugs to cause reflex bradycardia and tachycardia, respectively,in patients in whom wide and parallel variations in heart rateand blood pressure occurred in response to endogenous factorssuch as sedation and stress (Table 2). The diagnosis was supportedin most patients by historical, physical, and physiologic information.
Table 2. Cardiovascular Characteristics of 13 Patients with Baroreflex Failure.
Baroreflex function was determined at rest in supine patientsduring hospitalization by measuring heart-rate responses tostepwise bolus injections of phenylephrine until a dose wasfound that raised systolic blood pressure by 25 mm Hg or more;the estimated fall in heart rate for an increase of 25 mm Hgin pressure was used as an index of the baroreflex control ofheart rate. Similar studies were carried out with bolus injectionsof nitroprusside until a dose was found that lowered systolicblood pressure by 25 mm Hg. Changes in heart rate occurred withinthree minutes of drug administration. In four patients, thebaroreflex effect on heart rate was determined from the Valsalvamaneuver rather than by the administration of vasoactive drugs.
Causes of the baroreflex abnormalities in these patients areshown in Table 1. One patient had undergone surgical sectionof a glossopharyngeal nerve for intractable glossopharyngealneuralgia after a neck injury that had apparently damaged thecontralateral glossopharyngeal and vagal nerves. Three patientshad undergone surgery and radiation therapy for carcinoma ofthe pharynx. Four patients had the familial paraganglioma syndrome,a genetic disorder characterized by multiple benign non-catecholamine-producingtumors of the carotid body, glomus jugulare, and glomus vagale18;these tumors damage the glossopharyngeal and vagal nerves. Onepatient had marked cell loss in the nuclei of each solitarytract of the brain stem caused by a degenerative neurologicdisorder involving the brain stem and higher structures of thecentral nervous system; the cause was known from the resultsof an autopsy performed after the patient's death from pneumoniaapproximately one year after his evaluation. Finally, in twopatients, no cause of the baroreflex failure could be identified.
After diagnosis, we monitored variations in blood pressure,heart rate, and plasma catecholamine concentrations in eachpatient19. Blood pressure was measured every four hours whilethe patients were supine and upright and during symptomaticepisodes. Plasma catecholamine concentrations were measuredwhile the patients were supine and upright and during episodesof symptoms.
Cold pressor tests were executed by having supine subjects puttheir right hands in a basin filled with half ice and half waterfor 60 seconds. Blood pressure and heart rate were measuredbefore and at the end of this maneuver20. Mental-arithmetictests were performed by having supine subjects perform serialsubtractions of 7 beginning with the number 200. Blood pressureand heart rate were determined before and 60 seconds after thestart of the test. The isometric handgrip test was conductedas previously described20.
Propranolol, given in a dose of 1 mg per minute intravenouslyfor 10 minutes, and atropine, given as a bolus dose of 0.04mg per kilogram of body weight intravenously, were administeredto assess the sympathetic (beta1-adrenoreceptor) and parasympatheticcomponents of heart-rate control. Clonidine was given orallyat a dose of 0.1 mg, and blood pressure and heart rate weremonitored at 30-minute intervals during the succeeding 3 hours.The two-hour time point was used to determine to what degreeclonidine reduced sympathetic activity, as reflected by a changein blood pressure and plasma norepinephrine concentration17.
Twelve normal subjects were studied in a similar fashion. Inaddition, in 8 patients with essential hypertension and 12 patientswith autonomic failure due to the Bradbury-Eggleston syndrome,plasma catecholamine concentrations were measured and testsof responsiveness to clonidine and phenylephrine and the coldpressor test were administered. The Bradbury-Eggleston syndrome(idiopathic orthostatic hypotension) is a degenerative disorderassociated with the loss of peripheral sympathetic and parasympatheticnervous function21.
In seven patients with baroreflex failure, the relative efficacyof phenoxybenzamine (given in a daily dose of 10 to 80 mg orallyfor two to four days), clonidine (given in a daily dose of 0.3to 2.4 mg orally for two to four days), and placebo was assessedduring hospitalization. The number of blood-pressure surgesand the levels of blood pressure and tachycardia during thesesurges were tabulated.
These studies were performed at the Clinical Research Centerof Vanderbilt University. The protocol was approved by the institutionalreview board of the university, and all study subjects gaveinformed written consent.
A standard radioenzymatic method was used with catechol-O-methyltransferasefor the simultaneous differential assay of norepinephrine, epinephrine,and dopamine.
The results in the different groups were compared by analysisof variance and, when appropriate, unpaired t-tests. The therapeuticresponses of the patients were analyzed by paired t-tests. Two-tailedtests were used, and a P value of less than 0.05 was consideredto indicate statistical significance. The results are presentedas means ±SE.
Results
The defining features of baroreflex failure were an abilityof stress (increase in heart rate) or sedation (decrease inheart rate) to modify the heart rate, the absence of a tachycardicresponse to the hypotensive effect of nitroprusside, and theabsence of a bradycardic response to the pressor effect of phenylephrine12.In terms of these variables there was no overlap between thepatients with baroreflex failure and the normal subjects (Table 2).
All patients had labile hypertension, either constantly or episodically.Each of the three patients with sustained hypertension had hadtwo carotid-body tumors (chemodectomas) resected 3 to 20 yearsapart; none had had hypertension or symptoms of baroreflex failureafter the resection of the first tumor. After the resectionof the second tumor and the loss of glossopharyngeal- and vagal-nervefunction, the patients had sustained hypertension for 24 to72 hours followed by episodic hypertension.
In the patients in whom baroreflex failure developed more gradually(for example, those in whom it appeared months to years afterneck irradiation), there was no initial phase of sustained hypertension,as determined by a review of their history and medical records.Nevertheless, episodic hypertension was prominent and persistedduring the six-month to eight-year period of follow-up. Mostpatients had no decrease in blood pressure on standing (unlessthey were receiving phenoxybenzamine or were volume-depleted),and in at least four patients systolic blood pressure rose 10to 30 mm Hg with the assumption of upright posture.
The symptoms of baroreflex failure are shown in Table 1. Headache,tachycardia, diaphoresis, and flushing were generally presentonly during periods of blood-pressure elevation, which lastedfrom 3 to 30 minutes, and the highest blood pressures causedthe most devastating symptoms. Most patients also appeared tohave emotional lability, even between blood-pressure surges.
A typical episode of hypertension induced in a patient by acold pressor test is shown in Figure 1. The patient's bloodpressure was normal during the two hours preceding the test.The blood pressure continued to increase for approximately 10minutes after the test stimulus was removed, but ultimatelyreturned to base line. Similar hypertensive episodes occurredspontaneously and could be precipitated by even minor mentalarousal, such as mental-arithmetic calculations, in all patients,although most were less severe than the one illustrated in Figure 1.
Figure 1. Blood-Pressure Monitoring in a 43-Year-Old Man Approximately Two Weeks after Surgical Removal of a Carotid-Body Tumor and Five Years after Removal of a Contralateral Carotid-Body Tumor.
While blood pressure was being monitored, the patient's right hand was immersed in ice water for 60 seconds. The blood pressure immediately rose and continued to rise for several minutes after discontinuation of the cold stimulus. Symptoms appeared during this time and then resolved as blood pressure and heart rate returned to normal during the following 30 minutes. On some occasions, the patient had spontaneous paroxysms of similar magnitude.
Ten patients reported increased nervousness or emotional labilityafter the onset of their illness, in response to specific questioningabout it. The nervousness was more prominent in the patientswho had the greatest elevations in blood pressure, and it increasedduring blood-pressure elevations. During these elevations, thepatients also had a sensation of warmth with pallor (pale flushing),palpitations, and in the most severe episodes, headache anddiaphoresis. The constellation of symptoms thus closely resembledthat of patients with pheochromocytoma22. The diagnosis of pheochromocytomawas seriously considered at some time in virtually all thesepatients, but was ruled out by biochemical and radiographictests and also by the improvement, or at least the absence ofan increase, in hypertensive episodes during follow-up.
The mean extremes of blood pressure and heart rate during inpatientmonitoring are shown in Table 2 and Figure 2. The peak systolicblood pressures were significantly higher in the patients thanin the normal subjects, and the patients had lower systolicblood pressures (usually at night) than did the normal subjects.The heart rate generally paralleled blood pressure, with thesame wide variations. Two patients had heart rates above 90beats per minute at all times, possibly reflecting the partialloss of efferent parasympathetic control of the heart rate asa result of damage to the right vagal nerve.
Figure 2. Variations in Systolic Blood Pressure, Heart Rate, and Plasma Norepinephrine Concentrations in Patients with Baroreflex Failure and Normal Subjects.
The patients and normal subjects were monitored in a metabolic unit at rest and while ambulatory, but no vigorous exercise was permitted. MAX denotes maximum, and MIN minimum. The P values are for the comparison with normal subjects. To convert values for norepinephrine to nanomoles per liter, multiply by 0.005911.
The plasma norepinephrine concentrations changed in parallelwith the changes in blood pressure and to a lesser extent withthe changes in heart rate (Table 2 and Figure 2). The peak plasmanorepinephrine concentrations in the patients were significantlyhigher than those in the normal subjects. Plasma epinephrineconcentrations were also elevated during most attacks, in threepatients to more than 200 pg per milliliter (1.1 nmol per liter).Urinary excretion of epinephrine plus norepinephrine averaged118 µg per 24 hours (697 nmol per 24 hours), more thantwice normal (P = 0.015).
The cold pressor test elicited a much greater response in thepatients with baroreflex failure than in the normal subjects(Table 2). In some patients, the test initiated a hypertensiveparoxysm that continued for many minutes after the removal ofthe stimulus.
The hypotensive effect of clonidine in the patients was approximatelyfour times that in the normal subjects (Figure 3), but the responseto clonidine varied, depending on the initial blood pressure.The clonidine-induced fall in blood pressure was greater duringperiods of hypertension than during periods of normotension.The plasma norepinephrine concentrations decreased substantiallyin each of the 10 patients in whom they were measured. The mean(±SE) plasma norepinephrine concentration before clonidineadministration was 422 ±141 pg per milliliter (2.49 ±0.83pmol per liter), and two hours later it had fallen to 180 ±47pg per milliliter (1.06 ±0.28 pmol per liter, P = 0.021).
Figure 3. Fall in Systolic Blood Pressure in Response to Clonidine in Patients with Baroreflex Failure and Normal Subjects.
The heart-rate response to propranolol was dependent on theprevailing level of sympathetic activation; there was littleresponse when the blood pressure and heart rate were low. Duringepisodes of tachycardia, the heart rate decreased, with a meanfall of 12 beats per minute (range, 8 to 38) in patients withbaroreflex failure after they were given propranolol. The heartrate did not increase after the administration of atropine exceptwhen patients' blood pressures and heart rates were normal orlow. The mean increase in the heart rate in response to atropinewas 10 beats per minute (range, 7 to 15).
A comparison of the results of biochemical and pharmacologictests in patients with baroreflex failure, patients with essentialhypertension, and patients with autonomic failure caused bythe Bradbury-Eggleston syndrome is shown in Table 3. There weresignificant differences between the patients with baroreflexfailure and those with autonomic failure in all variables exceptthe bradycardic response to phenylephrine. There were also substantialdifferences in the results of most tests in the patients withbaroreflex failure and those with essential hypertension. Plasmanorepinephrine and epinephrine concentrations were higher andthe hypotensive and norepinephrine-lowering effects of clonidinewere greater in the patients with baroreflex failure. The moststriking difference was in the bradycardic response to phenylephrine,which was the defining characteristic of the group with baroreflexfailure.
Table 3. Comparison of Blood Pressure, Heart Rate, and Catecholamine Values in Patients with Baroreflex Failure, Autonomic Failure, and Essential Hypertension and in Normal Subjects.
Some patients with baroreflex failure required constant antihypertensivetherapy, so that the efficacy of different drugs could not besystematically assessed. In seven patients, however, it waspossible to compare the efficacy of clonidine, phenoxybenzamine,and placebo (Table 4). Clonidine, albeit over a very wide doserange, was effective in reducing both the frequency (P = 0.008)and severity (P = 0.013) of surges of hypertension and tachycardia,whereas phenoxybenzamine attenuated the increase in systolicblood pressure (P = 0.019) without decreasing the heart rateor reducing the frequency of attacks. Three patients had orthostatichypotension during treatment with phenoxybenzamine, as comparedwith one patient who was treated with clonidine. Supine bloodpressure was lower between as well as during attacks in patientsreceiving either drug. Eight patients were ultimately treatedwith clonidine patches. One patient was treated with methyldopa,but an unusually large daily dose (3750 mg orally) was requiredfor blood-pressure control.
Table 4. Results of Therapy on the Frequency and Severity of Pressor Surges in Seven Patients with Baroreflex Failure.
Over time, the dose of clonidine could be reduced in many patients.After two to four years, two patients discontinued clonidinetherapy and found that their hypertensive episodes could becontrolled most of the time with diazepam in a dose of 5 mgthree times daily.
Discussion
The powerful role of baroreflexes in blood-pressure controlin humans was shown by studies in which carotid baroreflex functionwas blocked by infiltrating the carotid-sinus region with procaine24,25.Bilateral blockade resulted in a substantial increase in systolicblood pressure (approximately 75 mm Hg) and heart rate (approximately50 beats per minute). During the course of these studies, severalsubjects had systolic blood pressures exceeding 300 mm Hg, thusproviding evidence that when patients with baroreflex nervelesions were ultimately identified, they would have severe hypertension.Comparable results were obtained in other patients by otherinvestigators26,27,28.
We found that clinical baroreflex failure may indeed cause severe,labile hypertension. The correlation of elevations in plasmanorepinephrine with pressor episodes suggests that these episodesare caused by unrestrained activation of the sympathetic nervoussystem. The possibility that vasopressin or other humoral pressoragents might also be released was not addressed in our study.A spectrum of clinical symptoms may accompany the hypertension,including headache, palpitation, a hot sensation, diaphoresis,and emotional lability. Our patients closely resembled the patientsdescribed by Kuchel et al.16 and Aksamit et al.,13 whose characteristicsare included in Table 2 (Patients 12 and 13, respectively).
There are several reasons for the heterogeneity in the clinicalexpression of baroreflex failure. Most severe symptoms occurwhen the interruption in the baroreflex is sudden -- for example,after surgery or injury. Indeed, in the first 24 to 72 hoursafter such bilateral nerve injury, the hypertension can be constantand may require the continuous infusion of nitroprusside orphentolamine. One patient (Patient 8) had several episodes ofapnea during the first 24 hours after surgery, perhaps becauseoxygen-sensing ability of the carotid body requires the integrityof the glossopharyngeal nerves for its information to be conveyedto the central nervous system. Subsequently, the episodes ofhypertension may become less frequent and the associated symptomsless dramatic.
Another explanation for the heterogeneity may be the degreeof baroreflex impairment in each patient. No patient had unilateralnerve damage. Even with bilateral nerve damage, there may bediffering degrees of involvement of the glossopharyngeal andvagal nerves, which are in close approximation throughout muchof their passage through the neck. One previously describedpatient with baroreflex failure had bilateral functional impairmentof the aortic baroreflex fibers carried in the vagal nerves,whereas the cardiopulmonary-reflex fibers, presumably travelingin the same nerve bundles, appeared to have been spared13.
Lesser degrees of baroreflex failure have occasionally beendetected with hemodynamic monitoring during or soon after carotidendarterectomy or carotid-body surgery29,30,31. The true incidenceof long-term elevations or lability of blood pressure aftersuch operative procedures is not known.
Three of our 11 patients with baroreflex failure had receivedradiation therapy to the neck, suggesting that patients undergoingthis therapy should be followed for the development of abnormalblood-pressure control. We17 and Aksamit et al.13 have previouslydescribed such patients. To our knowledge, no systematic assessmentof hypertension in this group of patients has been undertaken.
The two patients whom we classified as having idiopathic baroreflexfailure deserve special consideration. Their dysfunction maylie in the brain stem,32 although no abnormality was detectedin this structure by computed-tomographic scanning or magneticresonance imaging in one of these patients (these tests werenot done in the second patient). These two patients could havethe Page syndrome33 or a similar disorder16,34,35,36,37. ThePage syndrome is characterized by periodic blotchy flushingand perspiration of the face, upper chest, and occasionallythe upper abdomen, sometimes in association with cold extremities,headache, tachycardia, and hypertension33. Vascular compressionin the brain stem has also been proposed as a cause of somecases of hypertension38.
It is interesting to speculate why severe orthostatic hypotensiondoes not occur in the face of major damage to arterial baroreflexnerves, despite the suggestion that these reflexes are the principalmeans by which blood pressure is maintained in the upright posture.The simplest explanation is that some cardiopulmonary-reflexinformation is still being integrated. Alternatively, some othercompensatory mechanism may come into play during the assumptionof upright posture. In this regard, cardiovascular-control nucleiin the brain stem might receive information about posture froma number of sensory sources unconnected to the baroreflex. Forexample, information about position might be obtained from visualcues from the occipital cortex or other sites in the visualpathways, the cerebellum, and the neurovestibular system. Thesesources collectively might compensate for the absence of baroreflexes.
The clinical presentation of baroreflex failure bears an immediateand striking resemblance to that of pheochromocytoma22. In the1980s, Bravo et al. proposed that hypertensive patients withhigh plasma norepinephrine concentrations could be differentiatedfrom those with pheochromocytoma by the ability of clonidineto lower plasma norepinephrine concentrations in the formerbut not the latter39. Our patients had a 57 percent decreasein plasma norepinephrine after the administration of clonidine,similar to that reported by Bravo et al. in their patients withouttumor. These results indicate that this test is useful for rulingout pheochromocytoma. However, as shown in Table 3 and in previousreports,23 there is some overlap in clonidine responsivenessbetween patients with baroreflex failure and patients with essentialhypertension. This raises the possibility that baroreflex failuremay be the cause of labile hypertension in some patients withhyperadrenergic essential hypertension who have high plasmanorepinephrine concentrations. This could be readily ascertainedby measuring the heart-rate response to phenylephrine.
In conclusion, the manifestations of baroreflex failure in humansrange from an acute fulminant hypertensive crisis requiringurgent treatment with nitroprusside to a syndrome of habitualvolatility of blood pressure and heart rate with hypertensivesurges in response to stress, punctuated by periods of normalor even low blood pressure during rest. Differentiating baroreflexfailure from other causes of labile hypertension is essentialin devising effective treatment.
Supported in part by grants from the National Aeronautics andSpace Administration (NCC 2-696 and NAG 5-563) and the NationalInstitutes of Health (RR00095, HL44589, and HL37961).
We are indebted to Drs. Paul Kezdi, Allyn L. Mark, Donald J.Reis, James L. Young, Jr., and Dwain L. Eckberg for valuableinsights and to Ms. Dorothea Boemer and Ms. Jane Estrada forassistance in the preparation of the manuscript.
Source Information
From the Departments of Medicine (D.R., I.B., R.M.-G., R.M.R.), Pharmacology (D.R., I.B., R.M.-G.), Neurology (D.R.), and Otolaryngology (J.L.N.), Autonomic Dysfunction Center, Vanderbilt University, Nashville; and the Division of Clinical Pharmacology, University of Colorado Health Sciences Center, Denver (A.S.H.).
Address reprint requests to Dr. David Robertson at AA3228 MCN, Autonomic Dysfunction Center, Vanderbilt University, Nashville TN 37232-2195.
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Kaposi's Sarcoma
Washenik K., Clark-Loeser L., Friedman-Kien A., Simonart T., Vooren J.-P. V., Meuris S., Mazzone A., Ottini E., Paulli M., Antman K., Chang Y.
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63: 513-518
[Abstract][Full Text]
Goldstein, D. S., Eldadah, B. A., Holmes, C., Pechnik, S., Moak, J., Saleem, A., Sharabi, Y.
(2005). Neurocirculatory Abnormalities in Parkinson Disease With Orthostatic Hypotension: Independence From Levodopa Treatment. Hypertension
46: 1333-1339
[Abstract][Full Text]
Prilipko, O, Dehdashti, A R, Zaim, S, Seeck, M
(2005). Orthostatic intolerance and syncope associated with Chiari type I malformation. J. Neurol. Neurosurg. Psychiatry
76: 1034-1036
[Abstract][Full Text]
Heusser, K., Tank, J., Luft, F. C., Jordan, J.
(2005). Baroreflex Failure. Hypertension
45: 834-839
[Abstract][Full Text]
Taneja, I., Diedrich, A., Black, B. K., Byrne, D. W., Paranjape, S. Y., Robertson, D.
(2005). Modafinil Elicits Sympathomedullary Activation. Hypertension
45: 612-618
[Abstract][Full Text]
Tank, J., Diedrich, A., Szczech, E., Luft, F. C., Jordan, J.
(2004). {alpha}-2 Adrenergic Transmission and Human Baroreflex Regulation. Hypertension
43: 1035-1041
[Abstract][Full Text]
Timmers, H. J L M, Wieling, W., Karemaker, J. M, Lenders, J. W M
(2003). Denervation of carotid baro- and chemoreceptors in humans. J. Physiol.
553: 3-11
[Abstract][Full Text]
Singleton, C. D., Robertson, D., Byrne, D. W., Joos, K. M.
(2003). Effect of Posture on Blood and Intraocular Pressures in Multiple System Atrophy, Pure Autonomic Failure, and Baroreflex Failure. Circulation
108: 2349-2354
[Abstract][Full Text]
Furlan, R., Diedrich, A., Rimoldi, A., Palazzolo, L., Porta, C., Diedrich, L., Harris, P. A., Sleight, P., Biagioni, I., Robertson, D., Bernardi, L.
(2003). Effects of Unilateral and Bilateral Carotid Baroreflex Stimulation on Cardiac and Neural Sympathetic Discharge Oscillatory Patterns. Circulation
108: 717-723
[Abstract][Full Text]
Timmers, H. J.L.M., Karemaker, J. M., Wieling, W., Marres, H. A.M., Lenders, J. W.M.
(2003). Baroreflex Control of Muscle Sympathetic Nerve Activity After Carotid Body Tumor Resection. Hypertension
42: 143-149
[Abstract][Full Text]
Sharabi, Y., Dendi, R., Holmes, C., Goldstein, D. S.
(2003). Baroreflex Failure as a Late Sequela of Neck Irradiation. Hypertension
42: 110-116
[Abstract][Full Text]
Carson, R. P., Diedrich, A., Robertson, D.
(2002). Autonomic control after blockade of the norepinephrine transporter: a model of orthostatic intolerance. J. Appl. Physiol.
93: 2192-2198
[Abstract][Full Text]
Goldstein, D. S., Robertson, D., Esler, M., Straus, S. E., Eisenhofer, G.
(2002). Dysautonomias: Clinical Disorders of the Autonomic Nervous System. ANN INTERN MED
137: 753-763
[Abstract][Full Text]
Gutierrez, J, Santiesteban, R, Garcia, H, Voustianiouk, A, Freeman, R, Kaufmann, H
(2002). High blood pressure and decreased heart rate variability in the Cuban epidemic neuropathy. J. Neurol. Neurosurg. Psychiatry
73: 71-72
[Abstract][Full Text]
Ketch, T., Biaggioni, I., Robertson, R., Robertson, D.
(2002). Four Faces of Baroreflex Failure: Hypertensive Crisis, Volatile Hypertension, Orthostatic Tachycardia, and Malignant Vagotonia. Circulation
105: 2518-2523
[Abstract][Full Text]
Smit, A. A.J., Timmers, H. J.L.M., Wieling, W., Wagenaar, M., Marres, H. A.M., Lenders, J. W.M., van Montfrans, G. A., Karemaker, J. M.
(2002). Long-Term Effects of Carotid Sinus Denervation on Arterial Blood Pressure in Humans. Circulation
105: 1329-1335
[Abstract][Full Text]
Nikolsky, E., Patil, C. V., Beyar, R.
(2002). Ipsilateral Intracerebral Hemorrhage Following Carotid Stent-Assisted Angioplasty: A Manifestation of Hyperperfusion Syndrome: A Case Report. ANGIOLOGY
53: 217-223
[Abstract]
Conlin, P. R., Faquin, W. C.
(2001). Case 13-2001- A 19-Year-Old Man with Bouts of Hypertension and Severe Headaches. NEJM
344: 1314-1320
[Full Text]
Tank, J., Jordan, J., Diedrich, A., Stoffels, M., Franke, G., Faulhaber, H.-D., Luft, F. C., Busjahn, A.
(2001). Genetic Influences on Baroreflex Function in Normal Twins. Hypertension
37: 907-910
[Abstract][Full Text]
Jordan, J., Toka, H. R., Heusser, K., Toka, O., Shannon, J. R., Tank, J., Diedrich, A., Stabroth, C., Stoffels, M., Naraghi, R., Oelkers, W., Schuster, H., Schobel, H. P., Haller, H., Luft, F. C.
(2000). Severely Impaired Baroreflex-Buffering in Patients With Monogenic Hypertension and Neurovascular Contact. Circulation
102: 2611-2618
[Abstract][Full Text]
Tellioglu, T., Oates, J. A., Biaggioni, I.
(2000). Munchausen's Syndrome Presenting as Baroreflex Failure. NEJM
343: 581-581
[Full Text]
Phillips, A. M., Jardine, D. L., Parkin, P. J., Hughes, T., Ikram, H., Ikram, H.
(2000). Brain Stem Stroke Causing Baroreflex Failure and Paroxysmal Hypertension. Stroke
31: 1997-2001
[Abstract][Full Text]
Ahsan Ejaz, A., Meschia, J. F.
(1999). Thalamic Hemorrhage Following Carotid Endarterectomy-Induced Labile Blood Pressure: Controlling the Lability with Clonidine: A Case Report. ANGIOLOGY
50: 327-330
[Abstract]
Shannon, J. R., Jordan, J., Black, B. K., Costa, F., Robertson, D.
(1998). Uncoupling of the Baroreflex by NN-Cholinergic Blockade in Dissecting the Components of Cardiovascular Regulation. Hypertension
32: 101-107
[Abstract][Full Text]
Jordan, J., Shannon, J. R., Black, B. K., Lance, R. H., Squillante, M. D., Costa, F., Robertson, D.
(1998). NN-Nicotinic Blockade as an Acute Human Model of Autonomic Failure. Hypertension
31: 1178-1184
[Abstract][Full Text]
Biller, J., Feinberg, W. M., Castaldo, J. E., Whittemore, A. D., Harbaugh, R. E., Dempsey, R. J., Caplan, L. R., Kresowik, T. F., Matchar, D. B., Toole, J. F., Easton, J. D., Adams, H. P. Jr, Brass, L. M., Hobson, R. W. II, Brott, T. G., Sternau, L.
(1998). Guidelines for Carotid Endarterectomy : A Statement for Healthcare Professionals From a Special Writing Group of the Stroke Council, American Heart Association. Circulation
97: 501-509
[Full Text]
Biller, J., Feinberg, W. M., Castaldo, J. E., Whittemore, A. D., Harbaugh, R. E., Dempsey, R. J., Caplan, L. R., Kresowik, T. F., Matchar, D. B., Toole, J. F., Easton, J. D., Adams, H. P. Jr, Brass, L. M., Hobson, R. W. II, Brott, T. G., Sternau, L.
(1998). Guidelines for Carotid Endarterectomy : A Statement for Healthcare Professionals From a Special Writing Group of the Stroke Council, American Heart Association. Stroke
29: 554-562
[Full Text]
Shannon, J., Jordan, J., Costa, F., Robertson, R. M., Biaggioni, I.
(1997). The Hypertension of Autonomic Failure and Its Treatment. Hypertension
30: 1062-1067
[Abstract][Full Text]
Jordan, J., Shannon, J. R., Black, B. K., Costa, F., Ertl, A. C., Furlan, R., Biaggioni, I., Robertson, D.
(1997). Malignant Vagotonia Due to Selective Baroreflex Failure. Hypertension
30: 1072-1077
[Abstract][Full Text]
Naraghi, R., Schuster, H., Toka, H. R., Bahring, S., Toka, O., Oztekin, O., Bilginturan, N., Knoblauch, H., Wienker, T. F., Busjahn, A., Haller, H., Fahlbusch, R., Luft, F. C.
(1997). Neurovascular Compression at the Ventrolateral Medulla in Autosomal Dominant Hypertension and Brachydactyly. Stroke
28: 1749-1754
[Abstract][Full Text]
Lee, H. T., Brown, J., Fee, W. E. Jr
(1997). Baroreflex Dysfunction After Nasopharyngectomy and Bilateral Carotid Isolation. Arch Otolaryngol Head Neck Surg
123: 434-437
[Abstract]
Ille, O., Woimant, F., Pruna, A., Corabianu, O., Idatte, J. M., Haguenau, M.
(1995). Hypertensive Encephalopathy After Bilateral Carotid Endarterectomy. Stroke
26: 488-491
[Abstract][Full Text]
Robertson, D., Robertson, R. M.
(1994). Causes of Chronic Orthostatic Hypotension. Arch Intern Med
154: 1620-1624
[Abstract]
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