Biomedical subjects

Max J Hilz

Publications and source records attributed to Max J Hilz.

At least 19 recordsLinked to original sources

PubMed2006

Right ventromedial prefrontal lesions result in paradoxical cardiovascular activation with emotional stimuli.

Ventromedial prefrontal cortex (VMPFC) lesions can alter emotional and autonomic responses. In animals, VMPFC activation results in cardiovascular sympathetic inhibition. In humans, VMPFC modulates emotional processing and autonomic response to arousal (e.g. accompanying decision-making). The specific role of the left or right VMPFC in mediating somatic responses to non-arousing, daily-life pleasant or unpleasant stimuli is unclear. To further evaluate VMPFC interaction with autonomic processing of non-stressful emotional stimuli and assess the effects of stimulus valence, we studied patients with unilateral VMPFC lesions and assessed autonomic modulation at rest and during physical challenge, and heart rate (HR) and blood pressure (BP) responses to non-stressful neutral, pleasant and unpleasant visual stimulation (VES) via emotionally laden slides. In 6 patients (54.0 +/- 7.2 years) with left-sided VMPFC lesions (VMPFC-L), 7 patients (43.3 +/- 11.6 years) with right-sided VMPFC lesions (VMPFC-R) and 13 healthy volunteers (44.7 +/- 11.6 years), we monitored HR as R-R interval (RRI), BP, respiration, end-tidal carbon dioxide levels, and oxygen saturation at rest, during autonomic challenge by metronomic breathing, a Valsalva manoeuvre and active standing, and in response to non-stressful pleasant, unpleasant and neutral VES. Pleasantness versus unpleasantness of slides was rated on a 7-point Likert scale. At rest, during physical autonomic challenge, and during neutral VES, parameters did not differ between the patient groups and volunteers. During VES, Likert scores also were similar across the three groups. During pleasant and unpleasant VES, HR decreased (i.e. RRI increased) significantly whereas BP remained unchanged in volunteers. In VMPFC-L patients, HR decrease was insignificant with pleasant and unpleasant VES. BP slightly increased (P = 0.06) with pleasant VES but was stable with unpleasant VES. In contrast, VMPFC-R patients had significant increases in HR and BP during pleasant and not quite significant HR increases (P = 0.06) with only slight BP increase during unpleasant VES. Other biosignals remained unchanged during VES in all groups. Our results show that VMPFC has no major influence on autonomic modulation at rest and during non-emotional, physical stimulation. The paradoxical HR and BP responses in VMPFC-R patients suggest hemispheric specialization for VMPFC interaction with predominant parasympathetic activation by the left, but sympathetic inhibition by the right VMPFC. Valence of non-stressful stimuli has a limited effect with more prominent left VMPFC modulation of pleasant and more right VMPFC modulation of unpleasant stimuli. The paradoxical sympathetic disinhibition in VMPFC-R patients may increase their risk of sympathetic hyperexcitability with negative consequences such as anxiety, hypertension or cardiac arrhythmias.

Adult↗

PubMed2006

Impaired baroreflex function in temporal lobe epilepsy.

Changes of cardiovascular function are frequent in temporal lobe epilepsy (TLE). The baroreflex - the most important reflex for cardiovascular stability - has not been studied systematically in TLE. We evaluated cardiovascular variability and baroreflex function in TLE. In 22 TLE patients and 20 controls, we continuously monitored heart rate (HR) and blood pressure (BP). Time-domain parameters were derived from recordings at rest and from standard cardiovascular reflex tests. Spectral analysis determined sympathetic and parasympathetic modulation of HR and BP in the low (LF-power) and high frequency range (HF-power). We calculated the relative LF- and HF-powers of HR in relation to the sum of LF- and HF-powers. LF/HF-ratio of HR was assessed as a parameter of sympatheticovagal balance. LF-transfer function gain between BP and HR determined baroreflex function.Time-domain parameters did not differ between TLE patients and controls. Spectral analysis showed decreased absolute LF- and HF-powers but increased relative LF-power and LF/HF-ratio of HR in TLE. LF-transfer function gain between BP and HR was reduced in TLE (p<0.05). The reduction of absolute LF- and HF-powers indicates decreased total autonomic variability in TLE. However, increased relative LF-power and LF/HF-ratio of HR in TLE show a relative increase of sympathetic tone. Most importantly, we demonstrate an impaired baroreflex function in TLE. These cardiovascular autonomic abnormalities may contribute to cardiac arrhythmia in TLE.

Adult↗

PubMed2006

Quantitative studies of autonomic function.

Dysfunction of the peripheral and central autonomic nervous system is common in many neurological and general medical diseases. The quantitative assessment of sympathetic and parasympathetic function is essential to confirm the diagnosis of autonomic failure, to provide the basis for follow-up examinations, and potentially to monitor successful treatment. Various procedures have been described as useful tools to quantify autonomic dysfunction. The most important tests evaluate cardiovascular and sudomotor autonomic function. In this review, we therefore focus on standard tests of cardiovascular and sudomotor function such as heart-rate variability at rest and during deep breathing, active standing, and the Valsalva maneuver, and on the sympathetic skin response. These tests are widely used for routine clinical evaluation in patients with peripheral neuropathies. Refined methods of studying heart-rate variability, baroreflex testing, and detailed measures of sweat output are mostly used for research purposes. In this context, we describe the spectral analysis of slow modulation of heart rate or blood pressure, reflecting sympathetic and parasympathetic influences, and consider various approaches to baroreflex testing, the thermoregulatory sweat test, and the quantitative sudomotor axon reflex test. Finally, we discuss microneurography as a technique of direct recording of muscle sympathetic nerve activity.

Autonomic Nervous System↗

PubMed2006

Differential impairment of the sudomotor and nociceptor axon-reflex in diabetic peripheral neuropathy.

It is not known whether C-fiber functional subclasses are differentially affected by diabetes mellitus or whether the patterns of C-fiber dysfunction are different between type 1 and type 2 diabetes. We therefore examined efferent sympathetic sudomotor and primary afferent nociceptor C-fiber function in diabetic patients. Acetylcholine (10%) was used to evoke C-fiber (axon-reflex)-mediated responses. The nociceptor (flare) response was measured using a laser Doppler device. The sudomotor response was quantified with silastic imprints. The nociceptor C-fiber-mediated flare response was reduced in type 2 diabetic patients (P < 0.008) but was similar to controls in type 1 diabetic patients. The sympathetic C-fiber-mediated responses, including sweat volume (P < 0.05) and the number of activated sweat glands (P = 0.003), were increased in patients with type 1 diabetes. There also was a trend toward a larger axon-reflex sweat area in patients with type 1 diabetes (P = 0.09). No differences in these sweat responses were found in patients with type 2 diabetes compared to controls. These findings suggest that the functional abnormalities in diabetic peripheral neuropathy are not homogeneous and that C-fiber subclasses are differentially affected in type 1 and 2 diabetes mellitus.

Acetylcholine↗

PubMed2005

Effect of physical countermaneuvers on orthostatic hypotension in familial dysautonomia.

Familial dysautonomia (FD) patients frequently experience debilitating orthostatic hypotension. Since physical countermaneuvers can increase blood pressure (BP) in other groups of patients with orthostatic hypotension, we evaluated the effectiveness of countermaneuvers in FD patients. In 17 FD patients (26.4 +/- 12.4 years, eight female), we monitored heart rate (HR), blood pressure (BP), cardiac output (CO), total peripheral resistance (TPR) and calf volume while supine, during standing and during application of four countermaneuvers: bending forward, squatting, leg crossing, and abdominal compression using an inflatable belt. Countermaneuvers were initiated after standing up,when systolic BP had fallen by 40mmHg or diastolic BP by 30mmHg or presyncope had occurred. During active standing, blood pressure and TPR decreased, calf volume increased but CO remained stable. Mean BP increased significantly during bending forward (by 20.0 (17 - 28.5) mmHg; P = 0.005) (median (25(th) - 75(th) quartile)), squatting (by 50.8 (33.5 - 56) mmHg; P = 0.002), and abdominal compression (by 5.8 (-1 - 34.7) mmHg; P = 0.04) - but not during leg-crossing. Squatting and abdominal compression also induced a significant increase in CO (by 18.1 (-1.3 - 47.9) % during squatting (P = 0.02) and by 7.6 (0.4 - 19.6) % during abdominal compression (P=0.014)). HR did not change significantly during the countermaneuvers. TPR increased significantly only during squatting (by 37.2 (11.8 - 48.2) %; P = 0.01). However, orthopedic problems or ataxia prevented several patients from performing some of the countermaneuvers. Additionally, many patients required assistance with the maneuvers. Squatting, bending forward and abdominal compression can improve orthostatic BP in FD patients, which is achieved mainly by an increased cardiac output. Squatting has the greatest effect on orthostatic blood pressure in FD patients. Suitability and effectiveness of a specific countermaneuver depends on the orthopedic or neurological complications of each FD patient and must be individually tested before a therapeutic recommendation can be given.

Adolescent↗

PubMed2005

[Methods of quantitative evaluation of the autonomic nerve system].

Dysfunction of the autonomic nervous system is a frequent finding in many neurological and internal diseases. The quantitative assessment of cardiovascular and sudomotor function is important for diagnosing the autonomic impairment. In this review article, we focus on standard tests that allow evaluation of cardiovascular and sudomotor autonomic functions and describe methods of quantitative assessment that are better suited for research.

Autonomic Nervous System↗

PubMed2005

Abnormal heart rate and blood pressure responses to baroreflex stimulation in multiple sclerosis patients.

Cardiovascular autonomic neuropathy has been previously reported in patients with multiple sclerosis (MS) using standard reflex tests. However, no study has separately evaluated both parasympathetic and sympathetic cardiovascular autonomic regulation. We therefore assessed the baroreflex-mediated vagal and sympathetic control of the heart rate and sympathetic control of the blood vessels in MS patients using sinusoidal neck stimulation. We studied 13 multiple sclerosis patients aged 28-58 years and 18 healthy controls aged 26-58 years. The carotid baroreflex was stimulated by sinusoidal neck suction (0 to -30 mmHg) at 0.1 Hz to assess the autonomic control of the heart and blood vessels, and at 0.2 Hz to assess the vagal control of the heart. Continuous recordings were made of blood pressure, electrocardiographic RR-interval and respiration, with breathing paced at 0.25 Hz. Spectral analysis was used to evaluate the magnitude of the low frequency (LF, 0.03-0.14 Hz) and high frequency (HF, 0.15-0.50 Hz) oscillations in RR-interval and blood pressure in response to the sinusoidal baroreceptor stimulation. Responses to the applied stimulus were assessed as the change in the spectral power of the RR-interval and blood pressure fluctuations at the stimulating frequency from the baseline values. The increase in the power of 0.1 Hz RR-interval oscillations during the 0.1 Hz neck suction was significantly smaller (p<0.01) in the MS patients (4.47+/-0.27 to 5.62+/-0.25 ln ms(2)) than in the controls (4.12+/-0.37 to 6.82+/-0.33 ln ms(2)). The increase in the power of 0.1 Hz systolic BP oscillations during 0.1 Hz neck suction was also significantly smaller (p<0.01) in the MS patients (0.99+/-0.19 to 1.96+/-0.39 mmHg(2)) than in the healthy controls (1.27+/-0.34 to 9.01+/-4.10 mmHg(2)). Neck suction at 0.2 Hz induced RR-interval oscillations at 0.2 Hz that were significantly smaller (p<0.05) in the patients (3.22+/-0.45 ln ms(2)) than in the controls (5.27+/-0.29 ln ms(2)). These results indicate that in MS patients, baroreflex dysfunction is not only restricted to the cardiovagal limb of the baroreflex, but that the sympathetic modulation of the blood vessels is also affected.

Adult↗

PubMed2004

Assessing function and pathology in familial dysautonomia: assessment of temperature perception, sweating and cutaneous innervation.

This study was performed to assess cutaneous nerve fibre loss in conjunction with temperature and sweating dysfunction in familial dysautonomia (FD). In ten FD patients, we determined warm and cold thresholds at the calf and shoulder, and sweating in response to acetylcholine iontophoresis over the calf and forearm. Punch skin biopsies from calf and back were immunostained and imaged to assess nerve fibre density and neuropeptide content. Mean temperature thresholds and baseline sweat rate were elevated in the patients, while total sweat volume and response time did not differ from controls. The average density of epidermal nerve fibres was greatly diminished in the calf and back. There was also severe nerve loss from the subepidermal neural plexus (SNP) and deep dermis. The few sweat glands present within the biopsies had had reduced innervation density. Substance P immunoreactive (-ir) and calcitonin gene related peptide-ir (CGRP-ir) were virtually absent, but vasoactive intestinal peptide-ir (VIP-ir) nerves were present in the SNP. Empty Schwann cell sheaths were observed. Temperature perception was more impaired than sweating. Epidermal nerve fibre density was found to be profoundly reduced in FD. Decreased SP and CGRP-ir nerves suggest that the FD gene mutation causes secondary neurotransmitter depletions. Empty Schwann cell sheaths and VIP-ir nerves suggest active denervation and regeneration.

Adolescent↗

PubMed2004

Dynamic cerebral autoregulation is impaired in glaucoma.

OBJECTIVES: Autonomic and endothelial dysfunction is likely to contribute to the pathophysiology of normal pressure glaucoma (NPG) and primary open angle glaucoma (POAG). Although there is evidence of vasomotor dysregulation with decreased peripheral and ocular blood flow, cerebral autoregulation (CA) has not yet been evaluated. The aim of our study was to assess dynamic CA in patients with NPG and POAG. MATERIALS AND METHODS: In 10 NPG patients, 11 POAG patients and 11 controls, we assessed the response of cerebral blood flow velocity (CBFV) to oscillations in mean arterial pressure (MAP) induced by deep breathing at 0.1 Hz. CA was assessed from the autoregressive cross-spectral gain between 0.1 Hz oscillations in MAP and CBFV. RESULTS: 0.1 Hz spectral powers of MAP did not differ between NPG, POAG and controls; 0.1 Hz CBFV power was higher in patients with NPG (5.68+/-1.2 cm(2) s(-2)) and POAG (6.79+/-2.1 cm(2) s(-2)) than in controls (2.40+/-0.4 cm(2) s(-2)). Furthermore, the MAP-CBFV gain was higher in NPG (2.44+/-0.5 arbitrary units [a.u.]) and POAG (1.99+/-0.2 a.u.) than in controls (1.21+/-0.1 a.u.). CONCLUSION: Enhanced transmission of oscillations in MAP onto CBFV in NPG and POAG indicates impaired cerebral autoregulation and might contribute to an increased risk of cerebrovascular disorders in these diseases.

Adult↗

PubMed2004

Cerebral autoregulation improves in epilepsy patients after temporal lobe surgery.

Patients with temporal lobe epilepsy (TLE) often show increased cardiovascular sympathetic modulation during the interictal period, that decreases after epilepsy surgery. In this study, we evaluated whether temporal lobectomy changes autonomic modulation of cerebral blood flow velocity (CBFV) and cerebral autoregulation. We studied 16 TLE patients 3-4 months before and after surgery. We monitored heart rate (HR), blood pressure (BP), respiration, transcutaneous oxygen saturation (sat-O(2)), end-expiratory carbon dioxide partial pressure (pCO(2)) and middle cerebral artery CBFV. Spectral analysis was used to determine sympathetic and parasympathetic modulation of HR, BP and CBFV as powers of signal oscillations in the low frequency (LF) ranges from 0.04-0.15Hz (LF-power) and in the high frequency ranges from (HF) 0.15-0.5Hz (HF-power). LF-transfer function gain and phase shift between BP and CBFV were calculated as parameters of cerebral autoregulation. After surgery, HR, BP(mean), CBFV(mean), respiration, sat-O(2), pCO(2) and HF powers remained unchanged. LF-powers of HR, BP, CBFV and LF-transfer function gain had decreased while the phase angle had increased (p<0.05). The reduction of LF powers and LF-gain and the higher phase angle showed reduced sympathetic modulation and improved cerebral autoregulation. The enhanced cerebrovascular stability after surgery may improve autonomic balance in epilepsy patients.

Adult↗

PubMed2003

Outcome of epilepsy surgery correlates with sympathetic modulation and neuroimaging of the heart.

Temporal lobe epilepsy (TLE) is frequently associated with sympathetic over-activity. Single photon emission computed tomography (SPECT) with 123iodine-meta-iodobenzylguanidine (MIBG), a norepinephrine analogue, showed reduced tracer uptake in cardiac sympathetic nerve endings, indicating myocardial catecholamine disturbance. We investigated whether outcome of epilepsy surgery correlates with cardiac autonomic function in TLE patients. We studied 16 TLE patients before and after epilepsy surgery. We recorded heart rate (HR) and determined sympathetic and parasympathetic cardiac modulation as powers of low (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.5 Hz) heart rate oscillations. The LF/HF-ratio was calculated as index of sympathovagal balance. Cardiac MIBG uptake was assessed with MIBG-SPECT and compared to control data. After surgery, eight patients were seizure-free and eight had persistent seizures. Sympathetic LF-power and LF/HF-ratio were higher in patients who had persistent seizures than in patients who became seizure-free. After surgery, both parameters decreased in seizure-free patients but increased in patients with persistent seizures. MIBG uptake was lower in patients than controls and even lower in the patient subgroup who had persistent seizures. In this subgroup, MIBG uptake further decreased after surgery (P<0.05). Sympathetic cardiac modulation decreased in TLE patients after successful surgery, but further increased if seizures persisted. Reduction of cardiac MIBG uptake progressed after surgery in patients with persistent seizures. Interference of epileptogenic discharges with autonomic neuronal transmission might account for sympathetic cardiac over-stimulation and reduced MIBG uptake. Both findings are possible risk factors for sudden unexplained death and might be relevant for risk stratification in epilepsy patients.

3-Iodobenzylguanidine↗

PubMed2003

Cerebral autoregulation is compromised during simulated fluctuations in gravitational stress.

Gravity places considerable stress on the cardiovascular system but cerebral autoregulation usually protects the cerebral blood vessels from fluctuations in blood pressure. However, in conditions such as those encountered on board a high-performance aircraft, the gravitational stress is constantly changing and might compromise cerebral autoregulation. In this study we assessed the effect of oscillating orthostatic stress on cerebral autoregulation. Sixteen (eight male) healthy subjects [aged 27 (1) years] were exposed to steady-state lower body negative pressure (LBNP) at -15 and -40 mmHg and then to oscillating LBNP at the same pressures. The oscillatory LBNP was applied at 0.1 and 0.2 Hz. We made continuous recordings of RR-interval, blood pressure, cerebral blood flow velocity (CBFV), respiratory frequency and end-tidal CO(2). Oscillations in mean arterial pressure (MAP) and CBFV were assessed by autoregressive spectral analysis. Respiration was paced at 0.25 Hz to avoid interference from breathing. Steady-state LBNP at -40 mmHg significantly increased low-frequency (LF, 0.03-0.14 Hz) powers of MAP ( P<0.01) but not of CBFV. Oscillatory 0.1 Hz LBNP (0 to -40 mmHg) significantly increased the LF power of MAP to a similar level as steady-state LBNP but also resulted in a significant increase in the LF power of CBFV ( P<0.01). Oscillatory LBNP at 0.2 Hz induced oscillations in MAP and CBFV at 0.2 Hz. Cross-spectral analysis showed that the transfer of LBNP-induced oscillations in MAP onto the CBFV was significantly greater at 0.2 Hz than at 0.1 Hz ( P<0.01). These results show that the ability of the cerebral vessels to modulate fluctuations in blood pressure is compromised during oscillatory compared with constant gravitational stress. Furthermore, this effect seems to be more pronounced at higher frequencies of oscillatory stress.

Adaptation, Physiological↗

PubMed2003

Effect of cold face stimulation on cerebral blood flow in humans.

BACKGROUND AND PURPOSE: In humans, activation of the diving reflex by a cold stimulus to the face results in bradycardia, peripheral vasoconstriction and an increase in blood pressure. However, responses of the cerebral blood flow have not yet been evaluated. We undertook this study to assess the effect of cold face stimulation on the cerebral circulation in humans. METHODS: Seventeen healthy volunteers, aged 27+/-5 years were evaluated during application of a cold stimulus (0 degrees C) to the forehead for 60s. We continuously monitored mean arterial pressure (MAP), mean flow velocity (MFV) of the middle cerebral artery, cardiac output, skin blood flow, heart rate and end-tidal CO2. Total peripheral resistance (TPR) was calculated as MAP divided by cardiac output. Cerebrovascular resistance index (CVRi) was calculated as MAP divided by MFV. RESULTS: Cold face stimulation did not significantly affect cardiac output but resulted in significant decreases in heart rate and skin blood flow and an increase in MAP. MFV in the mid-cerebral artery showed a slight, but significant increase. The maximum increase in CVRi (14.2+/-11.4%) was significantly (P<0.01) less than the maximum increase in TPR (23.9+/-5.7%). End-tidal CO2 did not change significantly during the cold stimulation. CONCLUSIONS: In contrast to other sympathetic stimulations (e.g. lower body negative pressure), facial cooling results in an increase in cerebral blood flow. The amount of cerebral vasoconstriction was less than the amount of total peripheral vasoconstriction. These results suggest that although there is some constriction of the cerebral resistance vessels during cold face stimulation, cerebral perfusion was maintained, possibly by opposing parasympathetic activation.

Adult↗

PubMed2003

Assessment of cerebrovascular and cardiovascular responses to lower body negative pressure as a test of cerebral autoregulation.

The aim of this study was to determine whether lower body negative pressure (LBNP), combined with noninvasive methods of assessing changes in systemic and cerebral vascular resistance, is suitable as a method for assessing cerebral autoregulation. In 13 subjects we continuously assessed heart rate, blood pressure, cerebral blood flow velocity (CBFV) and cardiac output during graded levels of LBNP from 0 to -50 mm Hg. With increasing levels of LBNP, cardiac output declined significantly (to 55.8+/-4.5% of baseline value) but there was no overall change in mean arterial pressure. CBFV also fell at higher levels of LBNP (to 81.4+/-3.2% of baseline) but the percentage CBFV change was significantly less than that in cardiac output (P<0.01). The maximum increase in cerebrovascular resistance (pulsatility ratio) was significantly less than that in total peripheral resistance (17+/-6% vs. 105+/-16%, P<0.01). Spectral analysis showed that the power of low-frequency oscillations in mean arterial pressure, but not CBFV, increased significantly at the -50 mm Hg level of LBNP. These results show that, even during high levels of orthostatic stress, cerebral autoregulation is preserved and continues to protect the cerebral circulation from changes in the systemic circulation. Furthermore, assessment of cardiovascular and cerebrovascular parameters during LBNP may provide a useful clinical test of cerebral autoregulation.

Adult↗

PubMed2003

Heart rate-dependent electrocardiogram abnormalities in patients with postural tachycardia syndrome.

We recently published data suggesting the presence of an intrinsic sinus node abnormality in a subgroup of patients with the postural tachycardia syndrome (POTS). Based on the hypothesis that more widespread abnormalities of cardiac electrophysiologic properties may be present in POTS, we undertook a study to compare cardiac conduction and repolarization at different heart rate levels in patients with POTS and healthy controls. Eleven healthy controls and fourteen patients with POTS participated in the study. Acquisition of 12-lead electrocardiogram recordings were made during supine rest and during gradual head-up tilt. The heart rate of controls was titrated by isoproterenol infusion to match the heart rate of patients. Indices for cardiac conduction (PR interval, QRS duration, and R wave axis) and repolarization (QT interval, QTc interval, and T wave axis) were then compared at different heart rate levels. The PR interval decreased with increasing heart rate in controls more than in patients, resulting in a significantly longer PR interval in patients at the fastest heart rate level. The QT and QTc intervals were significantly shorter in POTS over the entire analyzed heart rate range. The T wave axis decreased with increasing heart rate in patients only. This resulted in a significantly lower T wave axis in patients at the fastest heart rate level. Our data suggest abnormalities of atrioventricular conduction and ventricular repolarization in patients with POTS. These findings may reflect intrinsic cardiac electrophysiologic abnormalities or may be secondary due to abnormalities of cardiac autonomic innervation.

Adult↗

PubMed2003

Postischemic cutaneous hyperperfusion in the presence of forearm hypoperfusion suggests sympathetic vasomotor dysfunction in Fabry disease.

In Fabry disease, deficiency of alpha-galactosidase A induces glycolipid storage that accounts for neuropathy, renal failure, myocardial infarction and stroke. Vascular crises may be precipitated by stressful conditions. To evaluate pathomechanisms of overall organ versus microvessel perfusion in response to ischemic challenge, we assessed resting and postischemic forearm and skin blood flow in Fabry patients. In 14 Fabry patients and 15 healthy controls, we measured resting and postischemic forearm blood flow by means of venous occlusion plethysmography and superficial index finger skin blood flow using laser Doppler flowmetry. At rest, arterial inflow into the limb was averaged from eight venous occlusion measurements and expressed as % volume change/minute. Postischemic plethysmographic inflow was determined from the peak influx during the first venous occlusion following three minutes of ischemia. Transcutaneous oxygen and carbon dioxide partial pressures at the forearm were monitored continuously. At rest, plethysmographic forearm perfusion was 15% lower in patients than in controls (p < 0.05) while skin blood flow did not differ between patients and controls. After ischemia, forearm hyperperfusion was less pronounced in patients than in controls (p < 0.05), while skin perfusion almost doubled in patients but increased only slightly in controls. Transcutaneous oxygen and carbon dioxide pressures did not differ between both groups. We conclude that the reduced overall limb perfusion at rest and after ischemia is likely to be due to lipid deposition with increased rigidity, decreased distensibility and lowered diameter of the vasculature. The exaggerated skin perfusion after ischemia might be attributable to the small fiber neuropathy of Fabry patients with deficient vasoconstrictor tone and enhanced vasodilatation due to hypersensitivity of denervated intracutaneous nerve fibers towards ischemia.

Adult↗

PubMed2003

Hereditary dysautonomias: current knowledge and collaborations for the future.

The hereditary dysautonomias (H-Dys) are a large group of disorders that affect the autonomic nervous system. Research in the field of H-Dys is very challenging, because the disorders involve interdisciplinary, integrative, and "mind-body" connections. Recently, medical scientists, NIH/NINDS representatives, and several patient support groups gathered for the first time in order to discuss recent findings and future directions in the H-Dys field. The H-Dys workshop was instrumental in promoting interactions between basic science and clinical investigators. It also allowed attendees to have an opportunity to meet each other, understand the similarities between the various forms of dysautonomia, and experience the unique perspective offered by patients and their families. Future advances in H-Dys research will depend on a novel multi-system approach by investigators from different medical disciplines, and it is hoped that towards a common goal, novel "bench-to-bedside" therapeutics will be developed to improve the lives of, or even cure, patients suffering from dysautonomic syndromes.

Animals↗

PubMed2003

Orthostatic challenge reveals impaired vascular resistance control, but normal venous pooling and capillary filtration in familial dysautonomia.

Patients with familial dysautonomia (FD) frequently have profound orthostatic hypotension without compensatory tachycardia. Although the aetiology is presumed to be sympathetic impairment, peripheral vascular responses to orthostasis have not been assessed. The aim of this study was to evaluate the control of vascular responses to postural stress in FD patients. Measurements of heart rate, blood pressure, cardiac stroke volume and cardiac output (CO), by impedance cardiography, and calf-volume changes, by impedance plethysmography, were taken from nine FD patients and 11 control subjects while supine and during head-up tilt. During leg lowering, we also assessed the venoarteriolar reflex by measuring skin red-cell flux. Head-up tilting for 10 min induced sustained decreases in mean arterial pressure in the FD patients, but not in the controls. Total peripheral resistance (TPR, i.e. mean arterial pressure/CO) increased significantly in the controls (39.8+/-6.8%), but not in the FD patients. Calf-volume changes during tilting, when normalized for the initial calf volume, did not differ significantly between the patients (4.62+/-1.99 ml.100 ml(-1)) and the controls (3.18+/-0.74 ml.100 ml(-1)). The vasoconstrictor response to limb lowering was present in the patients (47.7+/-9.0% decrease in skin red-cell flux), but was impaired as compared with the controls (80.7+/-3.4%) ( P <0.05). The impaired vasoconstriction during limb lowering and absent increase of TPR during tilting confirm that orthostatic hypotension in FD is due primarily to a lack of sympathetically mediated vasoconstriction without evidence of abnormally large shifts in blood volume towards the legs during orthostasis. This may be due, in part, to a preserved myogenic response to increased vascular pressure in the dependent vascular beds.

Adult↗