Spectral analysis of blood pressure and heart rate,catecholamine and neuropeptide Y plasma levels in a new model of neurogenic orthostatic hypotension in dog

The aim of the study was to compare changes in blood pressure (BP) and heart rate (HR) variability, catecholamine and neuropeptide Y (NPY) plasma levels induced by passive head-up tilt in normal and sino-aortic denervated (SAD) chloralose-anaesthetized dogs. In controls, 80° head-up tilt test failed to change BP and increased HR. Plasma noradrenaline and NPY levels (but not adrenaline) significantly rose. In SAD dogs, head-up tilt rest induced a marked and reproducible decrease in BP without any change in HR or noradrenaline and NPY plasma levels. In SAD dogs, spectral analysis in supine position was characterizied by reduced variability in the high frequency (HF) band of the HR spectrum without changes in low frequency (LF) bands of both HR and systolic blood pressure (SBP). Head-up tilt test increased the LF component of SBP variability and decreased the HF component of HR variability in controls but failed to modify HR and BP variabilities in SAD dogs. In conclusion, sino-aortic denervation in dogs elicits a reproducible postural fall in BP with impaired adaptation of sympathetic nervous system activity. This model may be of value in evaluating the pharmacological effects of drugs for the management of orthostatic hypotension.     

Microcirculation response to local cooling in patients with Huntington’s disease

Altered autonomic nervous system (ANS) functioning in early stages of Huntington's disease (HD) has been suggested, presumably due to distorted high-order autonomic control. ANS functioning in the early stages of HD was further investigated. Laser-Doppler (LD) flux in the skin of the fingertips, heart rate (HR), HR variability, systolic and diastolic blood pressure were measured during rest and during a 6 min cooling of one hand at 15°C. Data of 15 presymptomatic gene mutation carriers (PHD), 15 early symptomatic HD patients (EHD), and two groups of 15 age- and sex-matched controls were compared. The area under the low frequency (LF) and high frequency (HF) bands of the HR variability spectrum were calculated. An augmented reduction of cutaneous LD flux was found in response to the direct cooling in the PHD group (37.5 ± 8.5% of resting value) compared to the PHD controls (67.27 ± 8.4%) (p < 0.05). In addition, the PHD group had higher (LF/(LF + HF) index of primary sympathetic modulation of the HR at rest (53.6 ± 3.3) compared to the EHD patients (39.7 ± 4.2) (p < 0.05). In the EHD group, a significantly smaller change of HR during cooling (100.26 ± 1.2%) was found compared to the EHD controls (95.9 ± 1.0%) (p < 0.05). The results are in line with the hypothesis that ANS dysfunction occurs even in PHD subjects. Further, they support the hypothesis that dysfunction of the high-order autonomic centres are involved in HD.     

Dysfunctional baroreflex regulation of sympathetic nerve activity in remitted patients with panic disorder

Background Many researchers have studied the abnormalities of autonomic nervous system (ANS) such as decreased heart rate variability, which is a risk factor for sudden cardiac death, in patients with panic disorder (PD). However, no consistent abnormality has been uncovered to date. One of the reasons for this controversy may be due to the fact that most of these conventional studies have analyzed each physiological variable independent of other indices. We examined the ANS in PD patients using a new method which can more directly investigate the function of the baroreflex by examining the relation between the blood pressure (BP) and heart rate (HR). Methods During rest and audiovisual stimulation (AS) as mental stress such as being exposed to video imaginary of experiences such as driving motor vehicles, cardiovascular parameters, HR and BP were consecutively measured in 13 remitted PD patients and twenty aged and gender–matched normal controls (NC). In this study, to assess the cardiovascular ANS function (baroreflex) in PD we used the power spectrum analysis as usual and the mean of lag time (τ) between the Mayer wave components, which was closely related to sympathetic nerve activity of vasomotor, of HR and BP variability as a new trial. Results The PD patients and NC did not differ with regard to the power spectrum analysis of the heart rate. We found that τ in the PD group was significantly shorter than that in the NC both before and after AS, especially before. Conclusions These findings suggest that remitted PD patients may have a dysfunctional baroreflex regulation of sympathetic nerve activity.     

Levodopa, bromocriptine and selegiline modify cardiovascular responses in Parkinson's disease

Autonomic nervous system (ANS) involvement is frequently found in Parkinson's disease (PD), but its causal relationship to the disease itself and its medication is unclear. We evaluated the effects of PD medications on cardiovascular ANS functions. Heart rate (HR) responses to normal and deep breathing, the Valsalva manoeuvre and tilting, and blood pressure (BP) responses to tilting and isometric work were measured prospectively in 60 untreated PD patients randomised to receive either levodopa (n=20), bromocriptine (n=20) or selegiline (n=20) as their initial treatment. The results were compared with those of 28 healthy controls. The responses were recorded at baseline, after 6 months on medication and following a 6-week washout period. At baseline HR responses to normal breathing, deep breathing and tilting were already lower and the fall in the systolic BP immediately and at 5 min after tilting was more pronounced in the PD patients than in the controls. Six months' levodopa treatment diminished the systolic BP fall after tilting when compared to baseline, whereas bromocriptine and selegiline increased the fall in systolic BP after tilting and selegiline diminished the BP responses to isometric work. The BP responses returned to the baseline values during the washout period. The drugs induced no change in the HR responses. Thus PD itself causes autonomic dysfunction leading to abnormalities in HR and BP regulation and the PD medications seem to modify ANS responses further. Bromocriptine and selegiline, in contrast to levodopa, increase the orthostatic BP fall and supress the BP response to isometric exercise reflecting mainly impairment of the sympathetic regulation. Received: 17 February 2000 / Received in revised form: 25 May 2000 / Accepted: 15 June 2000     

Autonomic function in the early stage of panic disorder: power spectral analysis of heart rate variability

Previous studies of autonomic nervous system (ANS) function in panic disorder (PD) patients have yielded conflicting results. We speculate that these differences might result from the variety of clinical stages of PD. In order to investigate this, we compared ANS activity in untreated patients in the early stage of PD with control subjects using power spectral analysis of electrocardiogram R-R intervals (PSR-R) in supine rest and during head-up tilt, which was performed according to the maximum entropy method (MEM). It recognizes two main components: high-frequency power (HF), which mainly reflects cardiac parasympathetic activity, and low-frequency power (LF), which reflects both cardiac sympathetic and parasympathetic activity. The patients with PD had significantly higher values for all components of PSR-R only in tilt position total power (TP), LF, and HF than did the control subjects (P<0.01, <0.01, <0.02, respectively). However, the LF/HF ratio which indicated sympathovagal balance did not differ significantly between the two groups in tilt position. Our findings suggest that patients with PD in the early stage of illness have co-activation of sympathetic and parasympathetic nervous systems, which might act to maintain a balance between the two autonomic systems.     

Differential responding of autonomic function to histamine H1 antagonism in irritable bowel syndrome

Background The role of histamine in the pathophysiology of irritable bowel syndrome (IBS) is largely unknown. Dysfunction of the autonomic nervous system (ANS) in IBS patients is also not fully confirmed. We hypothesized that blockade of histamine H₁ receptors affects ANS responses differently between IBS subjects and controls. Methods Subjects were 12 IBS subjects and 12 age‐ and sex‐matched controls. Either 100 μg kg^?1 chlorphenamine or the same amount of saline was administered on different days. The rectum was stimulated with electrical currents of 0 mA (sham) or 30 mA. Autonomic nervous system function was measured using mean arterial pressure (MAP), heart rate (HR), high frequency (HF) component of HR variability, low frequency/high frequency ratio (LF/HF ratio) and plasma catecholamines and histamine. Subjective perceived stress during the examination was evaluated on an ordinate scale. Key Results Mean arterial pressure showed significant effects of diagnosis (P < 0.05) and drug × diagnosis interaction (P < 0.05). The MAP significantly increased after chlorphenamine administration in IBS subjects, but not in controls. Heart rate revealed a significant drug effect (P < 0.001), which decreased after chlorphenamine administration in controls, but not in IBS subjects. Perceived stress significantly increased by rectal stimulation (P < 0.001) and a significant stimulus × diagnosis interaction (P < 0.05) was revealed, indicating greater reduction in IBS subjects by chlorphenamine. Conclusion & Inferences Sympathetic vasomotor tone in IBS subjects differentially responded on administration of a histamine H₁ antagonist to that of controls. These findings suggest an increased histaminergic activity in IBS subjects.     

Major depression, heart rate, and plasma norepinephrine in patients with coronary heart disease.

BACKGROUND: Although it is now well established that psychiatric depression is associated with adverse outcomes in patients with coronary heart disease (CHD), the mechanism underlying this association is unclear. Elevated heart rate (HR) and plasma norepinephrine (NE), possibly reflecting altered autonomic nervous system activity, have been documented in medically well depressed psychiatric patients, and this pattern is associated with increased risk for cardiac events in patients with CHD. The purpose of this study was to determine whether autonomic nervous system activity is altered in depressed CHD patients. METHODS: HR, plasma NE, and blood pressure (BP) were measured in 50 depressed and 39 medically comparable nondepressed CHD patients at rest and during orthostatic challenge. RESULTS: Resting HR (p = .005), and the change from resting HR at 2, 5, and 10 min after standing (p = .02, .004, and .02, respectively), were significantly higher in the depressed than in the nondepressed patients. There were no differences between the groups in NE or in BP at rest, or in standing minus resting change scores at any time during orthostatic challenge (p < .05). CONCLUSIONS: Depression is associated with altered autonomic activity in patients with CHD, as reflected by elevated resting HR and an exaggerated HR response to orthostatic challenge. Previously reported differences in NE levels between depressed and nondepressed patients were not replicated.     

Symptom severity impacts sympathetic dysregulation and inflammation in post-traumatic stress disorder (PTSD)

Post-traumatic stress disorder (PTSD) is associated with a greater risk of incident hypertension and cardiovascular disease. Inflammation, impaired baroreflex sensitivity (BRS) decreased parasympathetic nervous system (PNS) and overactive sympathetic nervous system (SNS) activity are suggested as contributing mechanisms. Increasing severity of PTSD symptoms has been linked to greater cardiovascular risk; however, the impact of PTSD symptom severity on inflammation and autonomic control of blood pressure has not yet been explored. We hypothesized that increasing PTSD symptom severity is linked to higher inflammation, greater SNS activity, lower PNS reactivity and impaired BRS. Seventy Veterans participated in this study: 28 with severe PTSD ((Clinical Administered PTSD Scale (CAPS) > 60; S-PTSD), 16 with moderate PTSD (CAPS ≥ 45 ≤ 60; M-PTSD) and 26 Controls (CAPS < 45; NO-PTSD). We recorded continuous blood pressure (BP), heart rate (HR) via EKG, heart rate variability (HRV) markers reflecting PNS and muscle sympathetic nerve activity (MSNA) at rest, during arterial baroreflex sensitivity (BRS) testing via the modified Oxford technique, and during 3 min of mental stress via mental arithmetic. Blood samples were analyzed for 12 biomarkers of systemic and vascular inflammation. While BP was comparable between severity groups, HR tended to be higher (p = 0.055) in S-PTSD (76 ± 2 beats/min) than in Controls (67 ± 2 beats/min) but comparable to M-PTSD (70 ± 3 beats/min). There were no differences in resting HRV and MSNA between groups; however, cardiovagal BRS was blunted (p = 0.021) in S-PTSD (10 ± 1 ms/mmHg) compared to controls (16 ± 3 ms/mmHg) but comparable to M-PTSD (12 ± 2 ms/mmHg). Veterans in the S-PTSD group had a higher (p < 0.001) combined inflammatory score compared to both M-PTSD and NO-PTSD. Likewise, while mental stress induced similar SNS and cardiovascular responses between the groups, there was a greater reduction in HRV in S-PTSD compared to both M-PTSD and NO-PTSD. In summary, individuals with severe PTSD symptoms have higher inflammation, greater impairment of BRS, a trend towards higher resting HR and exaggerated PNS withdrawal at the onset of mental stress that may contribute to cardiovascular risk in severe PTSD.     

Cardiac autonomic modulation and blood pressure responses to isometric handgrip and submaximal cycling exercise in individuals with down syndrome

Purpose

Individuals with Down syndrome (DS) exhibit autonomic dysfunction, manifested as attenuated heart rate (HR) and blood pressure (BP) responses to sympathoexcitation. Whether a subgroup of individuals with DS with a normal HR response would have normal autonomic responses to sympathoexcitation remains unclear.

Methods

We compared autonomic modulation using HR variability (HRV) and BP responses in individuals with and without DS (controls) matched for the HR change to isometric handgrip (HG) (10 DS, 8 controls) and submaximal cycling exercise (CE) (9 DS, 9 controls). HG was performed for 2 min at 30 % of maximal voluntary contraction. CE included two 6-min stages at 0 W and at 50 % of body weight. Beat-to-beat HR and BP were recorded. HRV variables were natural log transformation (Ln) of low frequency (LF), high frequency (HF), LF/HF ratio, total power (TP), and the root mean square of successive differences (RMSSD).

Results

In the HG study, although individuals with DS exhibited an overall lower systolic BP, LF/HF ratio, and LnLF/LnHF, their BP and HRV responses to HG were similar to those of the controls. In the CE study, individuals with DS exhibited lower resting LnLF and an overall lower systolic BP and mean arterial pressure compared with controls. During the CE, individuals with DS exhibited an increased diastolic BP and a smaller reduction in LnTP than controls. These differences disappeared after controlling for confounders.

Conclusions

Our results suggest that despite normal HR responses to sympathoexcitatory tasks, HRV was largely similar to controls, with some evidence of autonomic dysfunction in individuals with DS.

     

Impaired autonomic control of heart rate and blood pressure in obesity: role of age and of insulin-resistance

The objectives of this study were to investigate cardiac and peripheral autonomic nervous system changes in normotensive overweight or obese subjects and the possible relation between these changes and insulin resistance independent of age. The authors used spectral analysis to measure simultaneously the short-term variability of heart rate (HR) and blood pressure (BP) using a Finapres device, in 67 normotensive over-weight or obese patients (age 37±12 y, body mass index [BMI]=37±9 kg/m²) and 45 never-obese subjects (controls; age 41±13 y, BMI 22±2 kg/m²). The spectral density was determined in three situations: subjects in the supine position, spontaneously breathing; subjects in the supine with controlled breathing; and subjects standing. The insulin sensitivity of overweight and obese subjects was determined from homeostatic model assessment (HOMA). The variability of normalized low-frequency (LF) spectral analysis of both HR and BP was lower in overweight or obese subjects than in controls, in the supine and standing positions (p<0.01). Normalized LF spectral analysis was negatively correlated to BMI independent of age, whatever the position. Homeostatic model assessment values were negatively correlated to the normalized LF spectral of HR, systolic BP and diastolic BP, in the standing position independent of BMI and age (p<0.05). Normalized high frequency (HF) of HR during controlled breathing decreased with age but not with BMI. In normotensive overweight or obese subjects, changes in sympathetic nervous system modulation are strongly correlated to insulin resistance. Decreased HR and BP variability could partly account for the higher cardiovascular risk and incidence of sudden death in obese persons.     

Influence of resting sympathetic activity on reflex sympathetic responses in normal man

Reflex sympathetic responses to physiologic stress are known to be modulated by afferent sensory mechanisms. However, the potential influence of baseline sympathetic tone on these reflex-mediated responses is unclear. To test the hypothesis that the resting level of muscle sympathetic nerve activity (MSNA) influences reflex-mediated changes in MSNA in normal man, MSNA, blood pressure (BP), central venous pressure (CVP), and heart rate (HR) was measured in 38 normal subjects at rest and during deactivation of cardiopulmonary baroreceptors (CPBR) with lower body negative pressure (LBNP; 0 to — 15 mmHg). A cold pressor test (CPT) also was performed in 25 subjects. Incremental LBNP decreased CVP (from 5.8 ± 0.4 to 2.1 ± 0.4 mmHg) without altering BP or HR, and increased in MSNA burst frequency (from 22.5 ± 1.4 to 30.2 ± 1.4 bursts/min). There was no significant correlation between levels of MSNA and any haemodynamic parameter at rest. There was a significant inverse correlation between CPBR sympathetic gain (CPBRSG, slope of the regression line correlating percentage change in MSNA (bursts/min) per mmHg decrease in CVP during non-hypotensive LBNP) and resting MSNA (r = -0.72,p < 0.0001). A significant inverse correlation was also observed between MSNA responses to the CPT (expressed as percentage change in burst frequency from control) and the resting MSNA (r = –0.63,p = 0.008). Sixteen subjects were restudied 3 weeks to 14 months later to determine reproducibility of measurements; resting BP and CVP, HR, and MSNA levels were not different between the two sessions, as was CPBRSG. In ten of these 16 subjects, in whom the CPT was repeated the MSNA response also was not significantly different. These studies demonstrate an inverse relationship between resting MSNA and both cardiopulmonary baroreflex sensitivity and sympathetic neural responses to the nonbaroreflex mediated cold pressor stimulus. These findings suggest that resting levels of sympathetic neural activity influence reflex-mediated changes in muscle sympathetic nerve activity.     

Cold pressor test demonstrates residual sympathetic cardiovascular activation in familial dysautonomia

In familial dysautonomia (FD), i.e. Riley-Day-syndrome, sympathetic cardiovascular function, as well as afferent temperature and pain mediating neurons, are significantly reduced. Thus, it was questioned if cold pressor test (CPT), which normally enhances sympathetic outflow and induces peripheral vasoconstriction by the activation of thermo- and nociceptive system activation, could be used to assess sympathetic function in FD.To evaluate whether CPT can be used to assess sympathetic activation in FD, we performed CPT in 15 FD patients and 18 controls. After a 35-min resting period, participants immersed their right hand and arm up to the elbow into 0-1 degrees C cold water while we monitored heart rate (HR), respiration, beat-to-beat radial artery blood pressure (BP), and laser Doppler skin blood flow (SBF) at the right index finger pulp. From these measurements, heart rate variability parameters were calculated: root mean square of successive differences (RMSSD), coefficient of variation (CV), low and high frequency (LF, HF) power spectra of the electrocardiogram (ECG).All participants perceived cold stimulation and indicated discomfort. In controls, SBF decreased and HR and BP increased rapidly upon CPT. After 60 s, SBF indicated secondary vasodilatation in six controls, BP rise attenuated and HR returned to baseline in all controls. In the patients, SBF remained unchanged, HR and BP increased significantly, but after 50-60 s of CPT and changes were lower than in controls (p<0.05). RMSSD and CV decreased and LF increased significantly only in the controls.We conclude that CPT activates sympathetic HR and BP modulation despite impaired pain and temperature perception in FD patients. BP increase in the presence of almost unchanged SBF might be due to HR increase and to nociceptive arousal and emotionally induced catecholamine release as seen in emotional crises of FD patients. CPT assesses sympathetic cardiovascular responses independently from baroreflex function, which is compromised in FD.     

Sympathetic nervous system activity in panic disorder

To assess sympathetic nervous system (SNS) activity in panic disorder, arterialized venous norepinephrine (NE) and epinephrine (EPI) were measured in 10 patients and 10 age- and weight-matched controls. In addition, arterialized plasma NE kinetics were determined using a tritiated NE isotope dilution technique. There were no significant differences between patients and controls for resting, supine plasma NE levels, plasma NE appearance rate, plasma NE clearance, or plasma cortisol. However, plasma EPI levels were significantly higher in panic patients (103 +/- 23 vs. 33 +/- 16 pg/ml). Furthermore, there was a significant correlation between anxiety ratings and plasma EPI levels in panic disorder patients. These findings suggest that during the resting state, panic disorder is associated with a selective activation of the adrenomedullary component of the SNS.     

Autonomic nervous system abnormalities predict cardiovascular changes after initiation of siponimod in secondary progressive multiple sclerosis

ObjectiveThe aim of this study was to identify whether autonomic nervous system (ANS) dysfunction identified prior to treatment initiation can predict siponimod related decrease in heart rate (HR) after treatment initiation.MethodsIn 26 people with secondary progressive multiple sclerosis (SPMS) the following ANS testing protocol was applied: 10-min supine resting position, Valsalva maneuver, deep breathing test, 10 min tilt-up table test, 5-min supine resting period, ingestion of siponimod, followed by 180-min supine resting period recordings. Heart rate variability (HRV) parameters were investigated as possible predictors of decrease in HR (ΔHR) after treatment initiation.ResultsAfter treatment initiation, there was a statistically significant drop in HR (71.1 ± 9.2 to 66.3 ± 8.1, p < 0.001) and elevation of systolic blood pressure (sBP) (113.2 ± 12.4 to 117.1 ± 10.8, p = 0.04). Values of the diastolic BP (dBP) followed similar trend as did sBP, however not reaching statistical significance (72.8 ± 9.6 to 74.9 ± 8.3, p = 0.13). In a multivariable regression model, disease duration and standard deviation of NN intervals (SDNN) were identified as independent predictors for ΔHR, where increase in SDNN and longer disease duration predict smaller ΔHR.ConclusionANS abnormalities may predict cardiovascular abnormalities associated with treatment initiation with siponimod.SignificanceResults of this study may help mitigate risks associated with siponimod treatment.     

Autonomic testing of women with interstitial cystitis/bladder pain syndrome

Purpose

Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by urinary urgency, frequency, nocturia, pain worse as the bladder fills and improved after emptying. These features might suggest abnormal autonomic bladder control mechanisms. We compared the structural integrity of the autonomic nervous system (ANS) in IC/BPS and control subjects.

Methods

IRB-approved study at University Hospitals Case Medical Center, Cleveland, OH to evaluate the structural integrity of the ANS in adult females. Testing included cardiovascular response to deep breathing, Valsalva maneuver, 30 min head up tilt, and sudomotor test.

Results

Differences in ANS integrity for IC/BPS subjects and controls were determined by modified Composite Autonomic Severity Score (CASS) that includes sudomotor, adrenergic and cardiovascular indices. Baseline heart rate (HR) and HRs from each of three 10 min upright segments of a tilt test were compared and trend analyses performed using t tests. Healthy and IC/BPS subjects were demographically similar. The two groups did not differ in modified-CASS scores but elevated average peak heart rate was evident during baseline (supine; p = 0.057) for IC/BPS subjects prior to a tilt test. Difference at baseline was maintained at each interval during the tilt, with nearly identical slopes across intervals. The preliminary nature of this report denotes a small sample size and important differences may not be detected.

Conclusions

The findings show no structural ANS abnormalities in IC/BPS subjects. Higher baseline HR supports the concept of functional rather than structural change in the ANS, such as abnormality of sympathetic/parasympathetic balance that will require further evaluation.     

Cardiovascular and hormonal responses to food ingestion in humans with spinal cord transection

In sympathetic denervation due to primary autonomic failure, ingestion of food causes a fall in blood pressure (BP) and exacerbates postural hypotension. It is not known whether these responses occur in tetraplegics with physiologically complete cervical spinal cord transection, who also have sympathetic dysfunction because of disruption of descending spinal sympathetic pathways. We, therefore, studied the effect of a liquid meal on BP, heart rate (HR) and neurohormonal levels in tetraplegics. Paraplegics with low lesions and without sympathetic dysfunction served as controls. After food ingestion, there was no fall in BP in tetraplegics or in controls. HR did not change in either group. After food, plasma noradrenaline was unchanged in tetraplegics, but rose in controls, while plasma renin activity (PRA) rose in tetraplegics but not in controls. The fall in BP and rise in HR on head-up tilt after the meal in tetraplegics was similar to that before the meal. There was no change in PRA following pre-prandial tilt in either group; postpprandial tilt raised levels in the tetraplegics, unlike in controls. Thus there is considerable variance in the responses to food between tetraplegics and paraplegic controls, and even greater differences when compared with published data in other autonomic disorders with sympathetic dysfunction; this may relate to the site and the nature of the sympathetic lesion and the ability to activate compensatory mechanism.     

Substances used and prevalence rates of pharmacological cognitive enhancement among healthy subjects

Several researches indicate that autonomic nervous system (ANS) dysfunction in patients with schizophrenia. Recently, salivary alpha-amylase (sAA) has been employed as a useful marker for ANS function. We investigated the extent of ANS dysfunction by measuring sAA and heart rate variability (HRV) of 25 patients with schizophrenia compared with controls. Schizophrenia group demonstrated a significant increase in sAA and markedly lower parasympathetic nervous system (PNS) activity in the HRV. However, there were no significant differences between two groups in sympathetic nervous system (SNS) activity. We concluded that PNS might be suppressed and the SNS shows relatively high activity in schizophrenia.     

Effects of subthalamic nucleus stimulation and levodopa on the autonomic nervous system in Parkinson's disease

Dysfunctions of the autonomic nervous system (ANS) are common in Parkinson's disease (PD). Regarding motor disability, deep brain stimulation of the subthalamic nucleus (STN) is an effective treatment option in long lasting PD. The aims of this study were to examine whether STN stimulation has an influence on functions of the ANS and to compare these effects to those induced by levodopa. Blood pressure (BP) and heart rate (HR) during rest and orthostatic conditions, HR variability (HRV) and breathing-induced cutaneous sympathetic vasoconstriction (CVC) were tested in 14 PD patients treated with STN stimulation during "ON" and "OFF" condition of the stimulator. The effects of a single dose of levodopa on ANS were tested in 15 PD patients without DBS. STN stimulation had no influence on cardiovascular ANS functions, whereas CVC was significantly increased. In contrast, levodopa significantly lowered BP and HR at rest and enhanced orthostatic hypotension. Further, HRV, skin perfusion and temperature increased after administration of levodopa. Our results suggest that in contrast to levodopa, STN stimulation has only minor effects on autonomic functions. Since less pharmacotherapy is needed after STN stimulation, reduced levodopa intake results in relative improvement of autonomic function in deep brain stimulated PD patients.     

Sympathetic nervous system, genes and human essential hypertension

The sympathetic nervous system (SNS) is the first line of defense in the response to environmental stress through its regulation of second-to-second changes in blood pressure (BP). Both the activity of the SNS and the therapeutic responses to SNS agonists and antagonists are known to be highly variable in the population. "Small" changes caused by single nucleotide polymorphisms (SNPs) of SNS genes may have considerable impact on SNS function and individualized hypertension treatment. In this review, we first describe the physiology of the SNS and its influence on cardiovascular and renal mechanisms of BP regulation. A thorough review of the role of genetic variability of various SNS genes in relation to the development of BP and essential hypertension (EH) follows. Given the vast number of SNS components, evaluations of multiple SNPs from multiple SNS genes are necessary for future association studies of BP and EH. One way to surpass the limitations and inconsistencies of previous association studies is to use a gene-based approach also referred to as indirect association, which takes all common variation within a candidate gene into account. In order to determine how SNS genes are differentially expressed or silenced, activated or inactivated against various environmental backgrounds, it is important to assess not only environmental and lifestyle risk factors such as diet, climate, chronic stress, but also personality characteristics such as hostility and coping styles. Uncovering relevant gene-gene and gene-environment interactions within the SNS cascade will not only enable early detection of EH risk but will also aid in the treatment of hypertensives through both non-pharmacological and pharmacological means.     

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. Received in revised form: 15 February 2006