Effects of head-up tilting on vagal nerve activity in man

OBJECTIVES: To evaluate the contribution of the vagal nerve activity in the cardiovascular postural adaptation, effects of decremental head-up tilting (90 degrees, 64 degrees, 53 degrees, 44 degrees, 37 degrees, 30 degrees, 24 degrees, 17 degrees, 12 degrees, 6 degrees and 0 degree) on time- and frequency-domain heart rate variability variables were analyzed in healthy young female. BACKGROUND: During head-up tilting, a hydrostatic venous pooling in the extremities occurs owing to gravity. To pump up the blood toward the upper body, the sympathetic nerve activity has been shown to play an important role. So, to date, few studies evaluated the effects of vagal nerve activity to stabilize the cerebral blood flow during head-up tilting. METHODS: Eight young female volunteers (age, 23.3 +/- 0.8 years; mean +/- SD) were evaluated. The electrocardiogram (ECG) by bipolar chest leads was recorded continuously during procedures, and the bed was tilted at 0.1 interval of sine function of tilting angle from upright position (90 degrees) to supine position (0 degree). The time domain measurements of cycle length variability (co-efficient of variance in percent for R-R intervals [CVRR], number of differences between adjacent R-R intervals that are > 50ms [RR50]) and the frequency domain measurements of low (0.08 to 0.15Hz, LF), high (0.15 to 0.40Hz, HF) and total (0.08 to 0.40, TF) power were performed to assess the cardiac sympathetic and vagal nerve activity. RESULTS: The CVRR showed no significant change during decremental head-up tilting, whereas the RR50 and the square root of HF power, more specific indices of cardiac parasympathetic tone, showed significant negative linear correlations to the sine of the tilting angle. In markers of cardiac sympathetic tone, there were significant positive correlations between the sine of the tilting angle and the normalized LF power or the LF-to-HF power ratio (LF/HF). CONCLUSION: These findings suggest that, in healthy young female, not only cardiac sympathetic nervous system but also cardiac vagal nervous system respond linearly to the change in body axis component of gravity, and they may contribute reciprocally and coordinately to cardiovascular postural adaptation.     

Application of USAF G-suit technology for clinical orthostatic hypotension: a case study

INTRODUCTION: The purpose of this study was to determine the effectiveness of a USAF anti-gravity suit (G-suit) on the stability of a patient with chronic orthostatic hypotension. METHODS: A 37-yr-old female with a history of insulin-dependent diabetes mellitus (IDDM) and symptomatic orthostasis was evaluated and the results were compared with those of non-diabetic controls, matched for age, height, and weight. Cardiac vagal tone was assessed by determination of standard deviation of 100 R-R intervals (R-R SD). We assessed the carotid-cardiac baroreflex response by plotting R-R intervals (ms) at each of eight neck pressure steps with their respective carotid distending pressures (mm Hg). Heart rate and blood pressure were recorded in response to the Valsalva maneuver (VM) performed at an expiratory pressure of 30 mmHg to assess integrated baroreflex responses. Blood pressures and heart rate were measured during three 5-min stand tests to assess orthostatic responses: a) without G-suit; b) with noninflated G-suit; and c) with inflated G-suit (50 mm Hg). RESULTS: The IDDM patient had minimal baseline cardiac vagal tone (R-R SD = 8.5 ms) compared with the average response of a control group of 24 subjects with orthostatic stability (R-R SD = 67.2 +/- 7.1 ms). Carotid-cardiac baroreflex response was virtually non-existent in the IDDM patient (Gain = 0.06 ms.mm Hg-1) compared to the control subjects (4.4 +/- 0.8 ms.mm Hg-1). VM responses corroborated the lack of cardiac baroreflex response in the IDDM patient, while blood pressure changes during the VM were similar to those of the controls. Upon standing, the IDDM patient demonstrated severe orthostatic hypotension (90 mm Hg SBP) and tachycardia without the G-suit. The G-suit, with and without pressure, reduced hypotension and tachycardia during standing. CONCLUSION: These results demonstrate successful application of Air Force technology as a useful alternative to pharmacologic intervention in the treatment of a patient with autonomic dysfunction leading to supine hypertension and orthostatic hypotension.     

Analysis of apoptosis in solid tumors by laser-scanning cytometry

BACKGROUND: This study determined the efficacy of venoconstrictive thigh cuffs, inflated to 50 mmHg, on impeding fluid redistributions during simulated microgravity. METHODS: There were 10 healthy male subjects who were exposed to a 2-h tilt protocol which started in the standing position, and was followed by 30 min supine, 30 min standing, 30 min supine, 30 min of -12 degrees head down tilt (HDT, to simulate microgravity), 15 min of HDT with venoconstrictive thigh cuffs inflated, a further 10 min of HDT, 5 min supine, and 10 min standing. To increase the sensitivity of the techniques in an Earth-based model, 12 degrees HDT was used to simulate microgravity effects on body fluid shifts. Volume changes were measured with anthropometric sleeve plethysmography. RESULTS: Transition to the various tilt positions resulted in concomitant decrements in leg volume (Stand [STD] to Supine [SUP], -3.0%; SUP to HDT, -2.0%). Inflation of the venoconstrictive thigh cuffs to 50 mmHg, during simulated microgravity, resulted in a significant 3.0% increase in leg volume from that seen in HDT (p < 0.01). No significant changes in systemic cardiovascular parameters were noted during cuff inflation. CONCLUSIONS: We conclude that venoconstrictive thigh cuffs, inflated to 50 mmHg for 15 min during 12 degrees HDT, can create a more Earth-like fluid distribution. Cuffs could potentially be used to ameliorate the symptoms of cephalad edema seen with space adaptation syndrome and to potentiate existing fluid volume countermeasure protocols.     

Assessment of baroreceptor-cardiac reflex sensitivity using time domain analysis in patients with IDDM and the relation to left ventricular mass index

Autonomic dysfunction in insulin-dependent diabetic (IDDM) patients has been associated with abnormalities of left ventricular function and an increased risk of sudden death. A group of 30 patients with IDDM and 30 age, sex and blood pressure matched control subjects underwent traditional tests of autonomic function. In addition, baroreceptor-cardiac reflex sensitivity (BRS) was assessed using time domain (sequence) analysis of systolic blood pressure and pulse interval data recorded non-invasively using the Finapres beat-to-beat blood pressure recording system. 'Up BRS' sequences-increases in systolic blood pressure associated with lengthening of R-R interval, and 'down BRS' sequences-decreases in systolic blood pressure associated with shortening of R-R interval were identified and BRS calculated from the regression of systolic blood pressure on R-R interval for all sequences. We also assessed heart rate variability using power spectral analysis and, after expressing components of the spectrum in normalised units, assessed sympathovagal balance from the ratio of low to high frequency powers. IDDM subjects underwent 2-D echocardiography to assess left ventricular mass index. Standard tests of autonomic function revealed no differences between IDDM patients and control subjects, but dramatic reductions in baroreceptor-cardiac reflex sensitivity were detected in IDDM patients. 'Up BRS' when supine was 11.2 +/- 1.5 ms/mmHg (mean +/- SEM) compared with 20.4 +/- 1.95 in control subjects (p < 0.003) and when standing was 4.1 +/- 1.9 vs 7.6 +/- 2.7 ms/mmHg (p < 0.001). Down BRS when supine was 11.5 +/- 1.2 vs 22 +/- 2.6 (p < 0.001) and standing was 4.4 +/- 1.9 vs 7.3 +/- 2.5 ms/mmHg (p < 0.003). There were significant relations between impairment of the baroreflex and duration of diabetes (p < 0.001) and poor glycaemic control (p < 0.001). From a fast Fourier transformation of supine heart rate data and using a band width of 0.05-0.15 Hz as low-frequency and 0.2-0.35 Hz as high frequency total spectral power of R-R interval variability was significantly reduced in the IDDM group for both low-frequency (473 +/- 62.8 vs 746.6 +/- 77.6 ms2 p = 0.002) and high frequency bands 125.2 +/- 12.9 vs 459.3 +/- 89.8 ms2 p < 0.0001. When the absolute powers were expressed in normalised units the ratio of low frequency to high frequency power (a measure of sympathovagal balance) was significantly increased in the IDDM group (2.9 +/- 0.53 vs 4.6 +/- 0.55, p < 0.002 supine: 3.8 +/- 0.49 vs 6.6 +/- 0.55, p < 0.001 standing). Thus, time domain analysis of baroreceptor-cardiac reflex sensitivity detects autonomic dysfunction more frequently in IDDM patients than conventional tests. Impaired BRS is associated with an increased left ventricular mass index and this abnormality may have a role in the increased incidence of sudden death seen in young IDDM patients.     

Effect of aerobic training on baroreflex regulation of cardiac and sympathetic function

To investigate the effect of aerobic exercise training on baroreflex regulation of muscle sympathetic nerve activity (MSNA) and cardiac R-R intervals in a middle-aged to older population, 10 healthy men > 40 yr of age underwent tests of autonomic function before and after 12 wk of high-intensity training. Cardiac and peripheral baroslopes were determined from the R-R interval vs. mean arterial pressure (MAP) and peroneal MSNA vs. diastolic pressure relationships, respectively, during sequential bolus injections of nitroprusside and phenylephrine. Maximal oxygen uptake increased (P < 0.05) 17% with training. Resting R-R interval increased (881 +/- 23 to 956 +/- 38 ms, P < 0.05), MAP decreased (96 +/- 2 to 91 +/- 3 mmHg, P < 0.05), and MSNA was unaltered (23.1 +/- 2.3 to 23.6 +/- 1.9 bursts/min) with training. Before and after training, respectively, cardiac baroslopes determined with decreasing (8.7 +/- 0.9 to 9.9 +/- 5.5 ms/mmHg) and increasing MAP (9.6 +/- 2.1 to 9.9 +/- 2.2 ms/mmHg) and the peripheral sympathetic baroslope (-3.3 +/- 0.4 to -3.5 +/- 0.6 bursts.min-1 x mmHg-1) did not differ. The results suggest that short-term aerobic training does not alter resting MSNA or neurocirculatory responses to baroreceptor challenges in middle-aged and older men.     

Analysis of vagal effects on ventricular rhythm in patients with atrial fibrillation

1. Animal studies suggest that the heart-rate-lowering effect of vagal stimulation during atrial fibrillation is due to: (1) a direct depressant effect on atrioventricular node conductivity, (2) enhancement of concealed atrioventricular nodal conduction of atrial impulses through augmenting fibrillatory activity, thereby indirectly prolonging atrioventricular nodal refractoriness. The purpose of the present study was to analyse these effects in man. 2. Sixteen patients with chronic atrial fibrillation were studied. After administration of propranolol (0.2 mg/kg intravenously) baseline ventricular rhythm was recorded (500 R-R intervals). Recordings were repeated after methylatropine (0.02 mg/kg intravenously). The shortest R-R interval was taken to represent atrioventricular nodal refractoriness. The ratio of the longest to the shortest R-R interval and the coefficient of variation of R-R intervals were used as parameters of concealed conduction. 3. Methylatropine foremost shortened long R-R intervals: values for the mean, shortest and longest R-R intervals decreased from 834 to 685 ms (-18%) (P < 0.001), 573 to 498 ms (-13%) (P < 0.001) and 1228 to 924 ms (-25%) (P < 0.001), respectively. Accordingly, the ratio of the longest to the shortest R-R interval decreased: 2.12 to 1.89 (-11%) (P < 0.05). Also, the coefficient of variation decreased: 0.24 to 0.20 (-17%) (P < 0.05). 4. This study supports the contention that vagal stimulation lowers ventricular rate during atrial fibrillation both by exerting a direct effect on the atrioventricular node and by augmenting concealed conduction.     

Time and frequency domain analyses of heart rate variability during orthostatic stress in patients with neurally mediated syncope

The role of autonomic balance during upright tilt in patients with neurally mediated syncope is unclear. To assess the characteristics of autonomic tone during orthostatic stress, 15 patients (mean age 32 years) with recurrent episodes of syncope (> or = 2) and a positive response to a 30-minute 60 degrees upright tilt were compared with the following control groups: (1) 15 patients (mean age 33.5 years) with > or = 2 episodes of recurrent syncope and a negative tilt response, and (2) 15 age- and sex-matched healthy volunteers (mean age 34 years) with no previous history of presyncope or syncope. Time domain measurements assessed were mean RR interval, standard deviation of normal RR intervals, and percentage of normal consecutive RR intervals differing by > 50 ms. Frequency domain measurements of the low-frequency (LF) and high-frequency (HF) bands were obtained, and the LF/HF ratio was also calculated. All variables were calculated in the supine position and during the first 5 minutes of upright tilt. No significant difference was observed in the time and frequency domain variables in the supine position between control groups with a negative head-up tilt response and the group with a positive response. The percentage of normal consecutive RR intervals differing by > 50 ms during the first 5 minutes of head-up tilt was significantly higher in the group with positive tilt tests than in the controls (25 +/- 12% vs 7 +/- 4%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Complex demodulation of cardiorespiratory dynamics preceding vasovagal syncope

BACKGROUND: The dynamic autonomic processes leading to vasovagal syncope are poorly understood. METHODS AND RESULTS: We used complex demodulation to continuously assess changes in respiration, R-R interval, and arterial pressure (blood pressure) variability during 60 degree head-up tilt in 25 healthy subjects with tilt-induced vasovagal syncope and 25 age-matched nonsyncopal control subjects. Coherence and transfer function analyses were used to examine the relation between respiration and R-R interval variability before syncope. Baseline blood pressure, R-R, and ventilation were similar between syncope subjects and control subjects. Syncope subjects experienced an increase in tidal volume and decrease in BP beginning 3 minutes before impending syncope (systolic blood pressure <80 mm Hg) necessitated termination of tilt. Approximately 90 seconds before syncope there was a sudden prolongation of R-R interval and increase in amplitude of high and low frequency R-R interval variability, indicating an abrupt enhancement of vagal tone. The increase in respiratory amplitude between 180 and 90 seconds before syncope was not accompanied by changes in R-R interval or R-R variability, suggesting a dissociation between respiration and the respiratory sinus arrhythmia. The coherence analysis showed fewer syncope subjects with coherence between respiratory and R-R interval variabilities and lower transfer magnitudes in syncope subjects compared with control subjects. Nonsyncopal subjects had no change in respiratory, R-R interval, or blood pressure dynamics during matched time periods before the time of syncope. CONCLUSIONS: Vasovagal syncope is preceded by a period of hyperpnea and cardiorespiratory decoupling followed by an abrupt increase in cardiovagal tone. Respiratory pumping without inspiratory cardiac slowing may partially counteract preload reduction until sudden bradycardia precipitates syncope.     

The importance of vitamin B 6 for development of the infant. Human medical and animal experiment studies

Thirteen healthy subjects were tested for parasympathetic reactivity during head-up tilt and reversal of the tilt. Head-up tilt (70 degrees) resulted in significant increase in baseline heart rate and diastolic blood pressure. Head-up tilt also led to increased parasympathetic reactivity as measured by Valsalva manoeuvre and hand grip test. Heart rate response to deep breathing test did not change. The reversal of the tilt led to returning of heart responses to original values. Responses indicate towards enhanced parasympathetic reactivity during head-up tilt position.     

Behavioral and electrocardiographic responses to social stress in male rats

Telemetry ECGs were recorded from Wistar male rats during social stress induced by exposure to aggressive lactating female rats. Behavioral response to maternal attack was evaluated in terms of relative duration of passive submissive (p/s) and active/nonsubmissive (a/ns) patterns. A decrease of R-R interval (R-R) compared to baseline conditions was found, significantly more pronounced than that observed in control animals exposed just to novel environment. R-R variability during social stress was positively correlated with the amount of p/s behavior. R-R fluctuations, episodes of II degree A-V block, and ventricular arrhythmias were also observed. Most R-R fluctuations and II degree A-V blocks were temporally associated with phases of p/s behavior and periods of high R-R variability. Ventricular arrhythmias generally appeared during a/ns behavior and were temporally linked with periods of low R-R variability. Ventricular arrhythmias, low R-R variability, and concomitant a/ns behavior might be related to an increased sympathetic activity. R-R fluctuations and II degree A-V blocks, associated with high R-R variability and p/s behavior, might be related to a predominant inhibitory effect of vagal activation (accentuated antagonism).     

Cardiac autonomic patterns preceding occasional vasovagal reactions in healthy humans

BACKGROUND: The wide range of clinical presentation of orthostatic vasovagal syncope suggests different underlying changes in the cardiac autonomic modulation. METHODS AND RESULTS: To evaluate the beat-by-beat modifications in the neural control of heart period preceding a syncopal event, we studied RR interval variability in 22 healthy subjects who experienced fainting for the first time during a 90 degrees head-up tilt and in 22 control subjects by means of time-variant power spectral analysis. Sympathetic and vagal modulations to the sinoatrial node were assessed by the normalized power of the low-frequency (LF, approximately 0.1-Hz) and high-frequency (HF, approximately 0.25-Hz) oscillatory components of RR variability. When the patients were supine, no differences were observed in the hemodynamic and spectral parameters of the 2 groups. During the tilt procedure, RR, LFNU, and HFNU (NU=normalized units) values were relatively stable in control subjects. During early tilt (T1), subjects with syncope had reduced RR intervals compared with control subjects. In 13 subjects with syncope, RR decreased while LFNU and LF/HF increased in the last minute of tilt before syncope (T2). Conversely, in the remaining 9 fainters, LFNU and LF/HF decreased from T1 to T2 and HFNU increased slightly. CONCLUSIONS: Two different patterns may be recognized in the cardiac autonomic changes preceding an occasional vasovagal event, namely, one characterized by a progressive increase of the marker of cardiac sympathetic modulation up to the onset of syncope, the other by a sympathetic inhibition with an impending vagal predominance. The recognition of different pathophysiological mechanisms in fainters may have important therapeutic implications.     

Face immersion increases vagal activity as assessed by heart rate variability

We examined whether the diving reflex without breath-holding (face immersion alone) increases vagal activity, as determined by heart rate variability. A group of 15 men [mean age 20 (SD 3) years, height 172 (SD 5) cm, body mass 68 (SD 9) kg] performed 12 trials at various breathing frequencies (5, 10, 15, 20, 30 breaths x min(-1) and uncontrolled breath) with or without face immersion. The R-R intervals of the ECG and gas exchange variables were recorded during the 2 min of each trial. The subjects immersed their faces in 8 10 degrees C water while breathing through a short snorkel. The subject sat in the same position either with or without face immersion. The mean R-R interval (RRmean), standard deviations (SD[RR]) and coefficient of variance (CV[RR]) of the R-R interval were calculated from the R-R intervals during 30-120 s. The face immersion significantly increased SD(RR) and CV(RR) (P < 0.05), and increased RRmean (P < 0.05) at 20 breaths x min(-1). Face immersion itself had no effect on oxygen uptake, tidal volume, end-tidal O2 and CO2 partial pressures. The diving reflex without breath-holding increased the heart rate variability, indicating that face immersion alone increases vagal activity.     

Time and frequency domain estimates of spontaneous baroreflex sensitivity provide early detection of autonomic dysfunction in diabetes mellitus

Diabetic autonomic dysfunction is associated with a high risk of mortality which makes its early identification clinically important. The aim of our study was to compare the detection of autonomic dysfunction provided by classical laboratory autonomic function tests with that obtained through computer assessment of the spontaneous sensitivity of the baroreceptor-heart rate reflex (BRS) by time domain and frequency domain techniques. In 20 normotensive diabetic patients (mean age +/- SD 41.9 +/- 8.1 years) with no evidence of autonomic dysfunction on laboratory autonomic testing (D0) blood pressure (BP) and ECG were continuously monitored over 15 min in the supine position. BRS was assessed as the slope of the regression line between spontaneous increases or reductions in systolic BP and linearly related lengthening or shortening in RR interval over sequences of at least 4 consecutive beats (sequence method), or as the squared ratio between RR interval and systolic BP spectral powers around 0.1 Hz. We compared the results with those of 32 age-matched normotensive diabetic patients with abnormal autonomic function tests (D1) and with those of 24 healthy age-matched control subjects with normal autonomic function tests (C). Compared to C, BRS was markedly less in D1 when assessed by both the slope of the two types of sequences (data pooled) and by the spectral method (-71.3% and -60.2% respectively, both p < 0.01). However, BRS was consistently although somewhat less markedly reduced in D0, the reduction being clearly evident for all the estimates (-57.0% and -43.5%, both p < 0.01). The effects were more evident than those obtained by the simple quantification of the RR interval variability. These data suggest that time and frequency domain estimates of spontaneous BRS allow earlier detection of diabetic autonomic dysfunction than classical laboratory autonomic tests. The estimates can be obtained by short non-invasive recording of the BP and RR interval signals in the supine patient, i.e. under conditions suitable for routine outpatient evaluation.     

Cardiac autonomic nerve function and insulin sensitivity in obese subjects

OBJECTIVE: To investigate whether obesity influences cardiac autonomic nerve function. DESIGN: Comparing two groups of subjects with different degrees of obesity to normal weight controls. SUBJECTS: 19 healthy controls (mean age 33 y, BMI 21.7 +/- 0.2 kg/m2) and 17 obese non-diabetic subjects (mean age 39 y, BMI 33.7 +/- 1.8 kg/m2). MEASUREMENTS: Insulin sensitivity was calculated by an oral glucose tolerance test. Autonomic nerve function was evaluated by analysing the variation of the heart frequency at rest (coefficient variation of R-R intervals, REST 1), during deep respiration, at a Valsalva maneuver (longest/shortest R-R interval during inspiration hold) and by the Ewing test (ratio between the 30th and 15th R-R interval after reaching up-right position). RESULTS: The obese showed a lower insulin sensitivity than healthy controls (3.09 vs 4.60 mg x l2/mmol x mU x min, P < 0.001). Their variation in heart frequency was reduced (REST 1: 1.95 vs 2.9, P < 0.01, Valsalva: 1.30 vs 1.52 and Ewing test: 1.03 vs 1.14, P < 0.05). However, patients with moderate (BMI 31.7 kg/m2) or severe obesity (39.0 kg/m2) with identical insulin sensitivity had no significant difference in autonomic nerve function. Except for the Ewing test all measured parameters for the evaluation of cardiac autonomic nerve function correlated with the degree of diminished insulin sensitivity (REST 1: r = 0.475, P < 0.001). CONCLUSION: Moderate obesity with significantly decreased insulin sensitivity is associated with impaired cardiac autonomic nerve function.     

Clinical and laboratory indices that enhance the diagnosis of postural tachycardia syndrome

OBJECTIVE: To identify clinical and laboratory indices that improve the diagnosis of the postural tachycardia syndrome (POTS). DESIGN: We assessed associations of orthostatic intolerance by using multivariate regression analysis. MATERIAL AND METHODS: We evaluated autonomic symptoms and autonomic function in 30 patients with POTS, 30 patients with mild orthostatic intolerance, and 19 age- and gender-matched control subjects. Indices of parasympathetic and sympathetic functions were analyzed on the basis of (1) autonomic function tests (head-up tilt), (2) oscillations at respiratory and nonrespiratory frequencies (0.01 to 0.09 Hz) in R-R interval and blood pressure (Wigner distribution), and (3) deterministic component (rescaled range analysis). RESULTS: The four clinical and laboratory indices that independently supported the diagnosis of POTS are as follows: (1) orthostatic heart rate during the first minute of head-up tilt, (2) autonomic deficit (adrenergic autonomic score), (3) loss of spectral powers in R-R interval during head-up tilt at the fifth minute, and (4) severity of orthostatic dizziness, fatigue, palpitations, and shortness of breath. CONCLUSION: Enhancing the sensitivity and specificity of the diagnosis of POTS should be possible by using these four indices. A hyperadrenergic state and distal neuropathy, affecting adrenergic sympathetic cardiovagal fibers, seem to be involved in the pathophysiology of POTS. Certain features suggest brain-stem dysregulation.     

Adhesion of leukocytes to growing arterial thrombi

BACKGROUND: The purpose of this study was to study the effect of enalapril on neurally mediated syncope (NMS). Several agents (except for angiotensin-converting enzyme [ACE] inhibitors) have been used to treat patients with NMS. It is unknown whether ACE inhibitors have beneficial effects on NMS. METHODS AND RESULTS: Thirty subjects who had reproducible NMS induced with head-up tilt table test (HUT) were randomly assigned and divided in double-blind fashion into placebo and enalapril (an ACE inhibitor) groups. Hemodynamics and plasma catecholamine concentrations were studied. Before administration of enalapril, syncope induced by HUT was associated with vigorous hypotension and bradycardia. Plasma catecholamine concentrations were significantly elevated during NMS compared with the supine position before tilt. Oral enalapril rather than placebo produced a marked reduction in diastolic blood pressure during supine positioning before tilt. Administration of enalapril prevented HUT-induced NMS and increase of plasma catecholamine concentrations in all patients examined. Conversely, placebo had no effect in the majority of patients with NMS (12 of 15 subjects). Follow-up data showed that NMS disappeared in 14 (93%) of 15 patients treated with enalapril. CONCLUSIONS: This study demonstrates that ACE inhibitors may efficiently prevent NMS, presumably through inhibition of sympathetic system activation and peripheral hypotensive effect.     

Endurance training, overtraining and baroreflex sensitivity in female athletes

We examined heavy training-induced changes in baroreflex sensitivity, plasma volume and resting heart rate and blood pressure variability in female endurance athletes. Nine athletes (experimental training group, ETG) increased intense training (70-90% VO2max) volume by 130% and low-intensity training (< 70% Vo2max) volume by 100% during 6-9 weeks, whereas the corresponding increases in six control athletes (CG) were 5% and 10% respectively. Maximal oxygen uptake (VO2max) in the ETG and CG did not change, but in five ETG athletes VO2max decreased from 53.0 +/- 2.2 (mean +/- SEM) (CI 46.8-59.2) ml kg-1 min-1 to 50.2 +/- 2.3 (43.8-56.6) ml kg-1 min-1 (P < 0.01), indicating overtraining. Baroreflex sensitivity (BRS) measured using the phenylephrine technique and blood pressure variability (BPV) did not change, but the low-frequency power of the R-R interval variability increased in the ETG (P < 0.05). The relative change in plasma volume was 7% in the ETG and 3% in the CG. The changes in BRS did not correlate with the changes in plasma volume, heart rate variability and BPV. We conclude that heavy endurance training and overtraining did not change baroreflex sensitivity or BPV but significantly increased the low-frequency power of the R-R interval variability during supine rest in female athletes as a marker of increased cardiac sympathetic modulation.     

Myofibroblastoma of the breast revisited: an etiologic association with androgens?

In order to test the hypothesis that normal gravity is an important influence on human serum [Erythropoietin] ([Epo]), the hematologic response to 16 d of 6 degrees head-down tilt (HDT, n = 6 men) was compared with 16 d of normal gravity exposure (CON, n = 7 men). Prior to bed rest, CON and HDT subjects, respectively, were similar in the following characteristics (mean +/- SD): age = 40 +/- 3, 39 +/- 6 yr; height = 181 +/- 5, 182 +/- 6 cm; weight = 88.5 +/- 11.3, 81.7 +/- 12.0 kg; maximal oxygen consumption in supine 6 degrees head-down tilt position (VO2max) = 2.63 +/- 0.38, 2.67 +/- 0.52 L.min-1; hematocrit = (Hct) 41.6 +/- 2.4, 43.0 +/- 3.4%; hemoglobin ([Hb]) = 15.1 +/- 1.0, 14.5 +/- 1.0 g.100 ml-1; plasma volume (PV) = 3829 +/- 857, 3768 +/- 512 ml; and [Epo] = 11.6 +/- 2.9, 10.0 +/- 6.2 mU.ml-1. Calculated red cell volume (RCV) was greater in HDT than CON (2845 +/- 410 vs. 2139 +/- 253 ml, p < 0.05) at baseline. Decreases in PV (-15%, 580 ml, p < 0.05) and an insignificant decrease in RCV (-12%, 354 ml, p = 0.07) were observed in the HDT group, with a concurrent 6% increase in [Hb] (p < 0.05). PV, RCV and [Hb] remained unchanged in the CON group. [Epo] remained unchanged during HDT (12.2 +/- 3.2; 10.8 +/- 3.8; 11.2 +/- 3.1; 11.2 +/- 2.6 mU.ml-1 for HDT days 1, 2, 8 and 16, respectively). There was no difference between CON and HDT groups in [Epo] before or during HDT. It was concluded that the insignificant change (-12%) in RCV observed during HDT was insufficient to stimulate an increase in [Epo], probably because the content of oxygen in arterial blood remained unaffected. The observation that [Epo] remained unchanged despite this loss of RCV during HDT also suggests a possible decrease in the responsiveness of the erythropoietic system to [Epo].     

Improved psychological well-being, quality of life, and health practices in moderately overweight women participating in a 12-week structured weight loss program

The first objective of this study was to confirm that 4 days of head-down tilt (HDT) were sufficient to induce orthostatic intolerance, and to check if 4 days of physical confinement may also induce orthostatic intolerance. Evidence of orthostatic intolerance during tilt-up tests was obtained from blood pressure and clinical criteria. The second objective was to quantify the arterial and venous changes associated with orthostatic intolerance and to check whether abnormal responses to the tilt test and lower body negative pressure (LBNP) may occur in the absence of blood pressure or clinical signs of orthostatic intolerance. The cerebral and lower limb arterial blood flow and vascular resistance, the flow redistribution between these two areas, and the femoral vein distension were assessed during tilt-up and LBNP by ultrasound. Eight subjects were given 4 days of HDT and, 1 month later, 4 days of physical confinement. Tilt and LBNP test were performed pre- and post-HDT and confinement. Orthostatic intolerance was significantly more frequent after HDT (63%) than after confinement (25%, P < 0.001). Cerebral haemodynamic responses to tilt-up and LBNP tests were similar pre- and post-HDT or confinement. Conversely, during both tilt and LBNP tests the femoral vascular resistances increased less (P < 0.002), and the femoral blood flow reduced less (P < 0.001) after HDT than before HDT or after confinement. The cerebral to femoral blood flow ratio increased less after HDT than before (P < 0.002) but remained unchanged before and after confinement. This ratio was significantly more disturbed in the subjects who did not complete the tilt test. The femoral superficial vein was more distended during post-HDT LBNP than pre-HDT or after confinement (P < 0.01). In conclusion, 4 days of HDT were enough to alter the lower limb arterial vasoconstriction and venous distensibility during tilt-up and LBNP, which reduced the flow redistribution in favour of the brain in all HDT subjects. Confinement did not alter significantly the haemodynamic responses to orthostatic tests. The cerebral to femoral blood flow ratio measured during LBNP was the best predictor of orthostatic intolerance.     

Long-term effects of pharmacological therapy for vasovagal syncope on the basis of reproducibility during head-up tilt testing

The purpose of this study was to determine the efficacy of long-term pharmacological therapy selected on the basis of a head-up tilt test (HUT) in patients in whom reproducibility of the HUT response was demonstrable in the initial study. The HUT (80 degrees upright) was performed for 15 min with or without an infusion of isoproterenol (0.01-0.03 microgram/kg per min) in 54 patients with recurrent unexplained syncope. When vasovagal syncope was induced (positive response), the HUT was repeated to examine the test reproducibility. Vasovagal syncope was induced in 24 patients during HUT alone, and in 30 patients during the HUT with isoproterenol. Acute reproducibility was observed in 49/54 (91%) patients. In the tilt-positive patients, HUT was repeated after an intravenous administration of propranolol (0.1 mg/kg) or disopyramide (1 mg/kg) (acute test). Propranolol proved effective in 21 (80%) of 26 patients, and disopyramide in 13 (56%) of 23 patients. Thereafter, evaluation was done on the long-term clinical follow-up of the pharmacological intervention selected on the basis of the acute test in the 34 patients in whom the HUT could not induce vasovagal syncope after the oral administration of the pharmacological agent (propranolol 60 mg/day, disopyramide 300 mg/day). Thirty-two of 34 patients (94%) did not develop syncopal attacks during a 44 +/- 12-month period. Thus, in patients with unexplained syncope, HUT appears to have a high degree of acute reproducibility, and the acute drug response guided by HUT may be used to develop an effective long-term pharmacological therapy.