Unveiling autonomic failure in synucleinopathies: Significance in diagnosis and treatment.

Autonomic failure is frequently encountered in synucleinopathies such as multiple system atrophy (MSA), Parkinson's disease (PD), Lewy body disease, and pure autonomic failure (PAF). Cardiovascular autonomic failure affects quality of life and can be life threatening due to the risk of falls and the increased incidence of myocardial infarction, stroke, and heart failure. In PD and PAF, pathogenic involvement is mainly post-ganglionic, while in MSA, the involvement is mainly pre-ganglionic. Cardiovascular tests exploring the autonomic nervous system (ANS) are based on the analysis of continuous, non-invasive recordings of heart rate and digital blood pressure (BP). They assess facets of sympathetic and parasympathetic activities and provide indications on the integrity of the baroreflex arc. The tilt test is widely used in clinical practice. It can be combined with catecholamine level measurement and analysis of baroreflex activity and cardiac variability for a detailed analysis of cardiovascular damage. MIBG myocardial scintigraphy is the most sensitive test for early detection of autonomic dysfunction. It provides a useful measure of post-ganglionic sympathetic fiber integrity and function and is therefore an effective tool for distinguishing PD from other parkinsonian syndromes such as MSA. Autonomic cardiovascular investigations differentiate between certain parkinsonian syndromes that would otherwise be difficult to segregate, particularly in the early stages of the disease. Exploring autonomic failure by gathering information about residual sympathetic tone, low plasma norepinephrine levels, and supine hypertension can guide therapeutic management of orthostatic hypotension (OH).

Intermittent versus constant aerobic exercise in middle-aged males: acute effects on arterial stiffness and factors influencing the changes.

PURPOSE: Both constant and intermittent acute aerobic exercises have been found to decrease arterial stiffness. However, direct comparisons of these two types of exercise are sparse. It is not known which type of exercise has the greatest effect. METHODS: We evaluated the haemodynamic responses in 15 males (age 48.5 ± 1.3 years; BMI 27.5 ± 0.8 kg m-2) following acute constant (CE) and intermittent cycling exercise (IE). Duration and heart rate were matched during both exercises (131.8 ± 3.2 bpm for CE and 132.0 ± 3.1 bpm for IE). Central and peripheral arterial stiffness was assessed through pulse wave velocity (PWV). Plasma concentrations of nitric oxide (NO), atrial natriuretic peptide (ANP), blood lactate, noradrenaline, and adrenaline were measured before and after each exercise. RESULTS: Central (+ 1.8 ± 7.4 and - 6.5 ± 6.8% for CE and IE) and upper limb PWV (+ 2.7 ± 6.2 and - 8 ± 4.6% for CE and IE) were not significantly altered although a small decrease (small effect size) was observed after IE. However, lower limb PWV significantly decreased after exercises (- 7.3 ± 5.7 and - 15.9 ± 4% after CE and IE), with a larger effect after IE. CONCLUSIONS: Greater decrease in lower limb PWV occurred after IE despite greater heart rate. This may be due to the higher blood levels of lactate during IE, while NO, ANP, noradrenaline, and adrenaline levels remained not statistically different from CE. These results underlined the importance of lactate in triggering the post-exercise vascular response to exercise, as well as its regional characteristic.

Changes in Tissue Oxygen Saturation in Response to Different Calf Compression Sleeves.

Aim. The purpose was to examine the changes in tissue oxygen saturation (StO2) in response to the application of different commercially available calf compression sleeves. Methods. Eight subjects came to the laboratory to complete a session in seated position including 10 min of quiet rest followed by 3 min measuring calf StO2 without compression sleeves and then alternating of 3 min of passive rest and 3 min measuring StO2 with calf compression sleeves. A total of 15 different commercially available compression sleeves were studied in a randomized order. Calf StO2 was recorded using near-infrared spectroscopy. Results. StO2 was significantly increased with all compression sleeves (p < 0.05) compared with no compression (from +6.9% for the least effective to +22.6% for the most effective). Large differences were observed between compression sleeves (p < 0.05). StO2 was positively correlated with compression pressure (p < 0.05; r = 0.84). Conclusion. This study shows that wearing compression sleeves from various brands differently affects tissue oxygen saturation. Differences were linked to the compression pressure: higher compression pressures were associated with higher StO2.

Changes in tissue oxygen saturation with calf compression sleeve: before, during and after a cycling exercise.

AIM: The purpose of this study was to examine the changes in tissue oxygen saturation (StO2) with calf compression sleeves, before, during and after a cycling exercise. METHODS: Eleven athletes came to the laboratory two times, to complete the same session with or without calf compression sleeves, in a randomized order. The session included a 15-min incremental cycling exercise: 3 min at each intensity - 40, 80, 120, 160 and 200 W, preceded (baseline) and followed (recovery) by a 10-min period at rest in seated position. Calf StO2 was recorded using near infrared spectroscopy during the three last min of the baseline period, during the cycling exercise and during the recovery period. RESULTS: Baseline StO2 was significantly increased with the compression sleeves (P<0.001; +24.8±3.5%). During the cycling exercise, StO2 was significantly increased with the compression sleeves only at 40 W (P<0.05; +8.2±3.7%) and 80 W (P<0.05; +7.9±3.7%). At 120 W (P=0.23; +5.0±4.0%), 160 W (P=0.38; +3.9±4.1%) and 200 W (P=0.81; -0.1±4.9%), no significant difference was found with compression sleeves. During the recovery period, StO2 was significantly increased with the compression sleeves (1 to 10 min: P<0.001; +10.5±1.3%). CONCLUSION: This study shows that wearing calf compression sleeves increases StO2 at rest (before and after an exercise) and at low intensities in cycling (40 W and 80 W). At high intensities (120 W and more), compression sleeves is not useful to increase StO2.

Effects of three postexercice recovery treatments on femoral artery blood flow kinetics.

AIM: This study aimed to compare the kinetics of muscle leg blood flow during three recovery treatments following a prolonged exercise: contrast water therapy (CWT), compression stockings (CS) or passive recovery (PR). METHODS: Fifteen men came to the laboratory three times to perform a 45-min exercise followed 5 min after by a standardized 12-min recovery treatment in upright position, alternating between two vats every 2 min: CWT (cold: ~12 °C to warm: 36 °C), CS (~20 mmHg) or PR. The order of treatments was randomized. Blood flow was measured using Doppler ultrasound during the recovery treatments (i.e., min 3, 5, 7 and 9) in the superficial femoral artery distally to the common bifurcation (~3 cm) (above the water and stocking). RESULTS: Blood flow was significantly higher during CWT (P<0.01; +22.91%) and CS (P<0.05; +15.26%) than during PR. Although no statistical difference between CWT and CS was observed, effect sizes were larger during CWT (large) than during CS (moderate). No changes in blood flow occurred in the femoral artery between hot and cold transitions of CWT. CONCLUSION: During immediate recovery of a high intensity exercise, CWT and CS trigger higher femoral artery blood flow than PR. Moreover, effect sizes were greater during CWT than during CS.

Changes in femoral artery blood flow during thermoneutral, cold, and contrast-water therapy.

AIM: The purpose of this study was to examine the changes in femoral artery blood flow during cold water immersion (CWI), contrast water therapy (CWT) and thermoneutral water immersion (TWI). METHODS: Ten athletes came to the laboratory three times, to complete a 20-min procedure in upright position: 4 min in air (baseline), then 16-min full leg TWI (~35 °C), CWI (~12 °C) or CWT (2:2 ~12 °C to ~35 °C) min ratio, in a random order. Blood flow was measured every 2 min: baseline (i.e. min 3 and 1) and throughout water immersion (i.e. min 1, 3, 5, 7, 9, 11, 13 and 15), using Doppler ultrasound in the superficial femoral artery, distal to the common bifurcation (~3 cm), above the water and stocking. RESULTS: Compared with baseline, blood flow was significantly higher throughout TWI (min 1 to 15: P<0.001; +74.6%), significantly lower during CWI (from min 7 to 15: P<0.05; -16.2%) and did not change during CWT (min 1 to 15). No changes in blood flow occurred between the hot and cold transitions of CWT. CONCLUSION: This study shows that external hydrostatic pressure (TWI ~35 °C) significantly increases femoral artery blood flow. We also show that associating hydrostatic pressure with cooling (CWI ~12 °C) decreases femoral artery blood flow after a sufficient duration, whereas associating hydrostatic pressure with alternating brief exposures to contrasted temperatures does not change femoral artery blood flow under resting conditions.

[COPD in dairy farmers: screening, characterization and constitution of a cohort. The BALISTIC study]. / BPCO des producteurs laitiers : dépistage, caractérisation et constitution d'une cohorte. Étude BALISTIC.

BACKGROUND: A pilot study from our group suggests that the prevalence of chronic obstructive pulmonary disease (COPD) among dairy farmers is higher than in the general population although dairy workers are less frequently smokers. OBJECTIVES AND METHODS: The study presented here aims at (i) determining the prevalence of COPD in a large and representative population of dairy farmers; (ii) characterizing these patients in terms of smoking habits, dyspnoea, quality of life, lung function, bronchial exhaled nitric oxide, systemic inflammation, arterial stiffness and exercise capacity; (iii) comparing characteristics of dairy farmers' COPD with the characteristics of COPD in patients without any occupational exposure; (iv) identifying the etiological factors of COPD in dairy farmers; and (v) constituting a cohort of COPD patients and control subjects for further longitudinal studies. Two groups of COPD patients (dairy farmers or not) and two groups of controls subjects will be selected among a representative panel of 2000 dairy workers and 2000 subjects without any occupational exposure, all aged 40 to 75 years. EXPECTED RESULTS: A better knowledge of the epidemiology and pathophysiology of COPD in dairy farmers should guide a specific strategy of prevention. The knowledge of the characteristics of COPD occurring in dairy farmers will help to define the therapeutic modalities that might be different compared with the therapeutic recommendations for COPD secondary to tobacco smoking.

Heart rate variability to assess ventilatory thresholds: reliable in cardiac disease?

BACKGROUND: The first (VT1) and second (VT2) ventilatory thresholds are landmarks to tailor exercise rehabilitation in coronary artery disease (CAD) or chronic heart failure (CHF). Methods allowing VT1 and VT2 determination based on heart rate variability (HRV) have been proposed but not yet evaluated in these patients. DESIGN: To determine the heart rate (HR) associated with VT1 and VT2 by three methods of HRV analyses. METHODS: Fourteen CHF and 24 CAD patients performed an exercise test on a cycle ergometer (10 -W every minute until exhaustion). VT1 and VT2 were determined with the 'respiratory equivalent' method. HR at VT1 was determined with the standard deviation (SD) of R⊟R intervals (VT(SD)) and of the instantaneous beat-to-beat variability of the Poincaré plot method (VT(Poincaré)). HR at VT1 and VT2 was determined through a time-varying HRV analysis method (VT(TV1) and VT(TV2), respectively). RESULTS: HR at VT(SD) was significantly higher than HR at VT1. No significant differences were observed between HR at VT(Poincaré), VT(TV1), and at VT1, nor between HR at VT(TV2) and VT2. HR at VT(SD), VT(Poincaré), and VT1 were significantly correlated, but with a low r (2) value and a large mean HR difference. With the time-varying method, the mean HR difference was lower than 5% and the correlation coefficients were higher (especially for VT(TV2)). CONCLUSIONS: SD and Poincaré plot methods lead to substantial inaccuracy in HR estimates. The time-varying HRV analysis led to strong correlation coefficients and low limits of agreement. Therefore, this method may be a promising, low-cost tool for non-invasive assessment of the ventilatory thresholds in cardiac disease.

Compression sleeves increase tissue oxygen saturation but not running performance.

The purpose of this study was to determine the effects of calf compression sleeves on running performance and on calf tissue oxygen saturation (StO2) at rest before exercise and during recovery period. 14 moderately trained athletes completed 2 identical sessions of treadmill running with and without calf compression sleeves in randomized order. Each session comprised: 15 min at rest, 30 min at 60% maximal aerobic velocity determined beforehand, 15 min of passive recovery, a running time to exhaustion at 100% maximal aerobic velocity, and 30 min of passive recovery. Calf StO2 was determined by near infra-red spectroscopy and running performance by the time to exhaustion. Compression sleeves increased significantly StO2 at rest before exercise (+ 6.4±1.9%) and during recovery from exercise (+ 7.4±1.7% and + 10.7±1.8% at 20th and 30th min of the last recovery period, respectively). No difference was observed between the times to exhaustion performed with and without compression sleeves (269.4±18.4 s and 263.3±19.8 s, respectively). Within the framework of this study, the compression sleeves do not improve running performance in tlim. However the StO2 results argue for further interest of this garment during effort recovery.

Exercise rehabilitation restores physiological cardiovascular responses to short-term head-out water immersion in patients with chronic heart failure.

PURPOSE: Rehabilitation programs increasingly involve immersed exercising, including inpatients suffering from severe cardiovascular diseases such as coronary artery disease (CAD) or chronic heart failure (CHF). The hemodynamic responses to short-term head-out water immersion are not well defined in these diseases. This study was aimed at evaluating (1) the cardiac and peripheral hemodynamic responses to short-term head-out water immersion in patients with CHF (n = 12) and CAD (n = 12) and (2) the effect of a rehabilitation program on these responses. METHODS: Wrist arterial tonometry was performed in the upright posture before and during immersion (1.30-m depth) once before and once after a 3-week rehabilitation program including gymnic water exercises. RESULTS: In patients with CAD, water immersion triggered a significant increase in stroke volume, cardiac output, and pulse pressure and a significant decrease in pulse rate, diastolic blood pressure, and systemic vascular resistances, both before and after the rehabilitation program. In patients with CHF, no significant immersion-linked changes in cardiovascular variables were observed before rehabilitation. However, after completion of the rehabilitation program, it was found that water immersion caused significant increases in stroke volume, cardiac output, and pulse pressure. CONCLUSION: In patients with CHF, this 3-week rehabilitation program restored the usual central responses to head-out water immersion (increase in stroke volume and cardiac output). In both patients with CHF and CAD, acute water immersion did not change arterial compliance.

Effects of the cold pressor test on cardiac autonomic control in normal subjects.

The cold pressor test (CPT) triggers in healthy subjects a vascular sympathetic activation and an increase in blood pressure. The heart rate (HR) response to this test is less well defined, with a high inter-individual variability. We used traditional spectral analysis together with the non-linear detrended fluctuation analysis to study the autonomic control of HR during a 3-min CPT. 39 healthy young subjects (23.7+/-3.2 years, height 180.4+/-4.7 cm and weight 73.3+/-6.4 kg) were divided into two groups according to their HR responses to CPT. Twenty subjects have a sustained increase in HR throughout the test with reciprocal autonomic interaction, i.e. increase in sympathetic activity and decrease vagal outflow. In the 19 remainders, HR decreased after an initial increase, with indication of involvement of both sympathetic and vagal outflow. Baseline evaluation of the subjects revealed no difference between the two groups. Nevertheless, a higher sympathetic activity at the skin level during CPT was present in the group with decreased HR. Further studies are needed to explain why healthy subjects react differently to the CPT and if this has potential clinical implications.

Delayed 24 hours Nomega-nitro-L-arginine methyl ester injection induces pharmacological cardioprotection against reperfusion injury.

Previous studies indicate that adenosine supplementation or nitric oxide synthase (NOS) inhibition during reperfusion exert protective effects against myocardial ischemia-reperfusion (I/R) injury. We wanted to test the hypothesis that NOS inhibition before I/R also protects the myocardium against further injury and aimed to determine the involvement of adenosine receptors in a perfused rat heart model. Rats were injected with 10 mg/kg of L-NAME (N(omega)-nitro-L-arginine methyl ester) or L-NAME + SPT (8-(p-sulfophenyl)-theophylline)--an adenosine antagonist - at 2 x 25 mg/kg or with a saline buffer, 24 hrs prior to heart excision. The hearts, perfused retrogradely were subjected to 60 min of global ischemia followed by 120 min reperfusion. L-NAME decreased NOx (nitrite and nitrate) production (16.2 +/- 3.2 vs. 7.0 +/- 1.8 micromol/L; P<0.05) in vivo and increased the release of troponin I (0.04 +/- 0.01 vs. 0.02 +/- 0.01 microg/L; P<0.05) in the plasma, compared to controls. After 120 min of reperfusion, there was a higher release of adenosine (26.1 +/- 2.2 vs. 2.4 +/- 1.2 nmol/min; P<0.01) and a decrease in troponin I levels (0.19 +/-0.07 vs. 0.59 +/- 0.16 ng/min; P<0.05) in the L-NAME group compared to controls. These results were accompanied by a higher proportion of recovery of left ventricular developed pressure (72.0 +/- 4.0 vs. 60.0 +/- 4.0%; P<0.05) and coronary flow (72.0 +/- 5.0 vs. 51.0 +/- 4.0%; P<0.05) in the L-NAME group. These beneficial effects were not blocked by the adenosine receptor antagonist. The present study reveals that L-NAME protects against I/R injury when the inhibitor is administered 24 hrs before ischemia. The beneficial effects observed in this model appear to be independent of adenosine receptor stimulation.

Impaired cardiovascular autonomic control in newly and long-term-treated patients with Parkinson's disease: involvement of L-dopa therapy.

In idiopathic Parkinson's disease (PD), autonomic dysfunction is frequent, causing orthostatic hypotension. The respective roles of disease progression and dopaminergic treatment remain unclear. In this study, we investigated the autonomic control of cardiovascular functions and its relation to L-dopa therapy in both newly diagnosed (ND) and long-term-treated (LT) patients. Study subjects were: (1) nine ND patients never having undergone treatment with L-dopa; (2) 18 LT patients who had been receiving L-dopa treatment for a long period. ND patients were investigated before L-dopa treatment and after stabilization of their L-dopa dosage. LT patients were investigated once with their regular treatment and once after a 12-h interruption of L-dopa treatment; (3) nine healthy subjects served as controls. At each test session, blood pressure (BP), heart rate (HR), plasma catecholamines, heart rate variability (HRV), and spontaneous baroreflex sensitivity were assessed in the supine and upright positions. Before receiving L-dopa medication, ND patients had reduced E/I ratios (HR response/deep breathing) and lowered HRV when compared to controls; this was evidence of early effects of the disease on autonomic HR control. Introduction of L-dopa treatment reduced BP, HR, and plasma levels of adrenaline and noradrenaline. Similar changes were found in LT patients when contrasting the short-term treatment interruption and the usual L-dopa dosage. The treatment-linked increase in plasma dopamine also correlated with the decrease in noradrenaline. These results showed that mild impairment of autonomic cardiovascular control occurred early in the course of PD. They also provided evidence that the side effects of L-dopa aggravated the impairment of the autonomic control of BP and HR.

Short-term vasomotor adjustments to post immersion dehydration are hindered by natriuretic peptides.

Many studies have described the physiology of water immersion (WI), whereas few have focused on post WI physiology, which faces the global water loss of the large WI diuresis. Therefore, we compared hemodynamics and vasomotor tone in 10 trained supine divers before and after two 6h sessions in dry (DY) and head out WI environments. During each exposure (DY and WI) two exercise periods (each one hour 75W ergometer cycling) started after the 3rd and 5th hours. Weight losses were significant (-2.24 +/- 0.13 kg and -2.38 +/- 0.19 kg, after DY and WI, respectively), but not different between the two conditions. Plasma volume was reduced at the end of the two conditions (-9.7 +/- 1.6% and -14.7 +/- 1.6%, respectively; p < 0.05). This post-WI decrease was deeper than post DY (p < 0.05). Cardiac output (CO) and mean arterial blood pressure were maintained after the two exposures. Plasma levels of noradrenaline, antidiuretic hormone and ANP were twofold higher after WI than after DY (p < 0.05). After DY total peripheral resistances (TPR) were increased (p < 0.05) and heart rate (HR) was reduced (p < 0.05). After WI there was a trend for a decrease in stroke volume (p = 0.07) with unchanged TPR and HR, despite more sizeable increases in plasma noradrenaline and vasopressin than after DY. We hypothesized that the higher levels of plasma natriuretic peptides after WI were likely counteracting the dehydration-required vasomotor adjustments.

[Effects of nitric oxide on cardioprotection prior to ischemia-reperfusion]. / Effets du monoxyde d'azote sur la cardioprotection avant l'ischémie-reperfusion.

This study aimed at evaluating the role of nitric oxide (NO) when generated 24 h prior to ischemia-reperfusion. Three groups were studied in an isolated buffer-perfused heart model: Control (saline = 3.3 mL/kg, n = 10), the precursor of NO, L-arginine, (500 mg/kg, n = 10) and an inhibitor of NO synthase, L-NAME, (10 mg/kg, n = 9). All groups were injected intraperitoneally 24 h before heart extraction. Nitrites, nitrates (an index of nitric oxide release) and cardiac troponine I were assayed. During the reperfusion period, there was a low release of nitric oxide and cardiac troponine I associated with improved recovery of post-ischemic myocardial function. These results indicate that in this model, the pre-treatment improved myocardial function and thus, NO could play a role as a trigger and not as a mediator of cardioprotection.

Graded vascular autonomic control versus discontinuous cardiac control during gradual upright tilt.

Indexes of heart rate variability (HRV) and the slope of cardiac baroreflex are extensively used for non invasive assessment of circulatory autonomic control in pathophysiology. We performed this study (1) to assess the sensitivity of these indexes towards small graded postural stimulations and (2) to delineate the informations provided about the settings of both vascular tone and cardiac activity. Twenty healthy subjects were randomly tilted for eight minutes at each of the six angles: -10 degrees, 0 degrees (supine), 10 degrees, 30 degrees, 45 degrees, and 60 degrees. Instant RR-interval and finger blood pressure (BP) were continuously recorded, and venous blood was collected at the end of each 8 min position for catecholamines determination. Group average heart rate, noradrenaline and diastolic BP (DBP) increased linearly with head-up tilt angle from 10 degrees. Systolic BP (SBB) ranked only two distinct series -10 degrees, 0 degrees, 10 degrees versus 30 degrees, 45 degrees, 60 degrees, as did the number of spontaneous baroreflex (SBR) sequences. The spectral power of the low-frequency (LF) and high-frequency (HF) of RR variability and the ratio LF/HF changed rather abruptly from either 30 degrees or 45 degrees, depending on each individual. Both HF/tot i.e. the ratio of HF to total spectral RR variability and the slope of SBR decreased markedly from 10 degrees to 30 degrees and less but more gradually from 30 degrees to 60 degrees. Thus, our observations argue for gradual adjustments of vascular tone as reflected by highly consistent changes in plasma noradrenaline and diastolic arterial pressure, contrasting with a main discontinuous autonomic setting of cardiac activity as reflected by changes in the harmonic components of spectral RR variability and in the slope of cardiac baroreflex. The pattern of changes in systolic arterial pressure attested the discontinuous cardiac autonomic control rather than the gradual setting of arterial tone. We submit that these different patterns of autonomic adjustments should be considered when assessing pathophysiological states.

Acute dysautonomia secondary to autoimmune diseases: efficacy of intravenous immunoglobulin and correlation with a stimulation of plasma norepinephrine levels.

Acute dysautonomia is a disorder characterized by severe sympathetic and parasympathetic failure with relative preservation of motor and sensory function. The disease is considered to be idiopathic in most cases, but there is now a trend towards considering the disorder as an uncommon variant of Guillain Barré syndrome. We report two cases of acute dysautonomia which did not fulfill the criteria of the idiopathic form. The first case was associated with Sjögren's syndrome and the second with thyroiditis and antiganglioside antibodies which were correlated with the severity of the disease. Intravenous gammaglobulin (IVGG) was effective in both cases, as has been reported for the idiopathic form, and in one case the treatment was associated with an increase in the supine and standing plasma norepinephrine levels, thus substantiating the positive effects of IVGG on the orthostatic blood pressure and heart rate. We conclude that the spectrum of acute dysautonomia is superimposable on that of the inflammatory peripheric neuropathies and should include both the idiopathic form and dysautonomia with autoimmune associated disorders. IVGG are effective and seems to act by increasing plasma norepinephrine levels.

Abnormal autonomic cardiovascular control in ankylosing spondylitis.

OBJECTIVE: This study was aimed at assessing the contribution of the autonomic nervous system to adjustments of cardiovascular function in patients with ankylosing spondylitis (AS). METHODS: In 18 AS patients (mean age: 34.9; mean disease duration: 6.4 years) and 13 healthy controls (mean age: 31.7) the changes of heart rate (HR) with deep breathing (E/I ratio) and standing up (30/15 ratio) were recorded. The slope of cardiac baroreflex, the times series of blood pressure and HR values upon lying and standing, and venous plasma concentrations of catecholamines were also analysed. Erythrocyte sedimentation rate (ESR), plasma C reactive protein (CRP) concentration and a clinical index (BASDAI score) were used to assess the degree of disease activity in patients. RESULTS: In the standing patients, blood pressure was found to decrease progressively (p< 0.001). Furthermore, the patients with a BASDAI score > 5 had a higher heart rate than patients with a BASDAI score < 5 (p<0.02), and there was a trend for a similar difference when patients were classified according to their ESR and CRP. Plasma catecholamine concentrations and the E/I ratio were not different in patients from controls. The 30/15 ratio and the slope of the spontaneous baroreflex during standing were both lower in AS patients than controls (p< 0.01). CONCLUSIONS: This study demonstrated a change in autonomic nervous system function of AS patients, with a decreased parasympathetic activity, as evidenced by higher HR and lower baroreflex slope. As these significant deviances were mainly observed in patients with more active (or more inflammatory) disease, the autonomic nervous system involvement could be related to the inflammatory process. This autonomic strain may be related to the cardiac involvement in AS patients.

Structural and immunohistological modifications in olfactory bulb of the staggerer mutant mouse.

In the present study, we describe the structural and cytological changes observed in staggerer mutant olfactory bulbs, as compared to normal mice. On the basis of photonic and ultrastructural observations we tried to define the alterations induced by the mutation: i.e. a reduction of bulb size, a reduction in the volume of three out of the six architectonic layers (glomerular, external and internal plexiform), a reduction of glomeruli size, a loss of half the mitral cells and a slight decrease in juxtaglomerular interneuron number. In staggerer, an hypertrophy of glial ensheathing cell processes was especially evident at the level of each glomerulus, whereas the density of the astrocyte network was weaker in the granular layer and the nerve layer not apparently impaired. An immunofluorescent labelling study combined with confocal scanning microscopy was performed in order to identify the cellular type and the differentiation degree of the various elements. Antibodies anti-GFAP, a protein present in both ensheathing cells and astrocytes, and anti-OMP, the specific maturation protein of the nerve layer, were used for that purpose. Data confirmed the reality of the gliosis and the persistence of the sensory component in the mutant. All the structural alterations described in staggerer olfactory bulb were in close agreement with the functional troubles previously recorded. Our results are discussed in connection with the present knowledge on embryonal origin, fetal development and adult cellular renewal of the olfactory bulb.

Active standing and passive tilting similarly reduce the slope of spontaneous baroreflex in healthy subjects.

Non-invasive assessment of the sensitivity of cardiac baroreflex was performed by recording each RR-interval and each blood pressure cycle (Finapres). In sequences of at least three cardiac cycles in which systolic blood pressure and RR-interval had changed in the same direction, the slope of linear regression of RR duration as a function of the change in systolic arterial pressure was taken for estimating the sensitivity of the spontaneous cardiac baroreflex. This technique was used in healthy humans to examine how a postural change from supine to upright by either active standing up or 60 degrees head-up tilting modified the sensitivity of the spontaneous baroreflex. We observed that the slope of the spontaneous baroreflex averaged 14.6 +/- 2 ms.mm Hg-1 during rest in the supine position, and decreased to 7.8 +/- 1.2 ms.mm Hg-1 (p < 0.05) after active standing, while the number of sequences was significantly increased in the upright as compared to the supine position. Head-up tilting by 60 degrees led to values similar to those following active standing. The adjustment of baroreflex slope to either postural change occurred in a few seconds, so that posture-characteristic values were obtained from five-minute records. We conclude that non-invasive recording of spontaneous sequences of related changes in blood pressure and RR-interval during several minutes provides reproducible values of the slope of cardiac baroreflex in the supine and upright position. This easy and reliable determination of the sensitivity of the cardiac baroreflex might prove to be useful when assessment of baroreflex function is needed.