Parasympathetic activity increases with digital microvascular damage and vascular endothelial growth factor in systemic sclerosis.

OBJECTIVES: The imbalance between angiogenic and angiostatic factors with derangement of the microvasculature are hallmarks of systemic sclerosis (SSc). Raynaud's phenomenon in SSc probably is due to the impaired neuroendothelial control mechanisms between vasoconstriction and vasodilatation. The aim of this study is to evaluate autonomic nervous system function using heart rate variability (HRV) analysis and to correlate with vascular endothelial growth factor (VEGF). METHODS: Twenty-seven SSc patients were enrolled. HRV was measured and markers of global sympathetic and parasympathetic system, respectively standard deviation of normal-to-normal RR intervals (SDNN) and square root of the mean of the sum of the squares of differences between adjacent NN intervals (RMSSD) were evaluated. Serum VEGF levels and nailfold videocapillaroscopy (NVC) were performed. RESULTS: A linear positive correlation was observed between RMSSD and VEGF (p<0.01, r=0.55), and RMSSD and disease duration (p< 0.01, r=0.54). The RMSSD median value was significantly increased (p< 0.05) with NVC damage progression. The RMSSD median value was significantly (p<0.05) higher in SSc patients with digital ulcers (DUs) than in SSc patients without DUs [44 (39.4-60.2) vs 24.6 (23-37.1)]. CONCLUSIONS: In our study parasympathetic modulation increases in relation to VEGF. When microcirculation is modified with capillaroscopic pattern progression and DUs, autonomic system seems to stimulate vasodilatation trough parasympathetic system. We can conclude that parasympathetic activity increases with digital microvascular damage and promotes VEGF release.

Effects of autonomic dysfunction on exercise tolerance in systemic sclerosis patients without clinical and instrumental evidence of cardiac and pulmonary involvement.

OBJECTIVES: Autonomic dysfunction (AD) in systemic sclerosis (SSc) was already confirmed through heart rate variability (HRV) analysis. Cardio-pulmonary exercise testing (CPET) is a useful tool in early detection of exercise tolerance in SSc patients. Aim of the study was to assess the relationships existing between AD and exercise tolerance. METHODS: Thirty-two [4 M, 28 F; median age: 47.5 (20-65) years] consecutive SSc patients were enrolled. All patients underwent pulmonary function testing, incremental symptom-limited CPET and twenty-four hours ECG Holter recording with HRV analysis in time and frequency domain. Multiple regression analysis was performed in order to identify independent HRV predictors of exercise tolerance and cardiac efficiency during the effort. RESULTS: HRV analysis showed significant differences in power in low and high frequency (LF and HF, respectively) and their ratio (LF/HF) compared to healthy controls. Nocturnal ratio be- tween power in low and high frequency at HRV (LF/HFnight) was shown to be the only independent positive predictor of maximal work load (R2=18.6%, p=0.014) and maximal oxygen consumption (V' O2 peak) expressed both as absolute value (R2=24.2%, p=0.004) and as corrected for body weight (R2=21.6%, p=0.007). A positive linear relationship was also found between nocturnal LF (LFnight) and the oxygen uptake/work rate (V'O2/W) slope (R2=15.8%, p=0.024). CONCLUSIONS: In SSc patients without cardiopulmonary involvement AD is associated with better exercise tolerance and cardiac function during physical effort. Further studies are needed to confirm these results.

QTc interval prolongation in HIV-infected patients: a case-control study by 24-hour Holter ECG recording.

BACKGROUND: Aim of the study was to assess QTc interval by a 24-hour ECG recording in a group of HIV-infected individuals with a basal prolonged QTc. The risk factors associated with QTc prolongation and the indices of cardiovascular autonomic control were also evaluated. METHODS: A case-control study was performed using as cases 32 HIV-infected patients with prolonged (>440 msec) QTc interval as assessed by Holter ECG, and as controls 64 HIV-infected subjects with normal QTc interval. Autonomic function was evaluated by heart rate variability analysis during 24-hour recording. RESULTS: Duration of HIV disease was significantly longer among cases than among controls (p=0.04). Waist/hip ratio was also higher among cases than among controls (p=0.05). Frequency domain analysis showed the absence of physiologic decrease of low frequency (LF) in the night period in both cases and controls. The LF night in cases showed a statistically significant reduction when compared with controls (p=0.007). CONCLUSIONS: In our study group, QTc interval prolongation was associated with a longer duration of HIV infection and with a greater waist/hip ratio. HIV patients with QTc interval prolongation and with a longer duration of HIV infection were more likely to have an impairment of parasympathetic and sympathetic cardiac component.

Role of autonomic dysfunction in the regulation of myocardial blood flow in systemic sclerosis evaluated by cardiac magnetic resonance.

AIM: Autonomic dysfunction (AD) is an early feature of systemic sclerosis (SSc). A regular endothelial function is a prerequisite for normal response of the myocardial blood flow (MBF) to cold pressure test (CPT). The aim of the study was to evaluate the relation between MBF and AD at rest and after CPT in asymptomatic SSc patients. METHODS: Twenty SSc patients and 10 age-, sex- and body mass index-matched healthy controls underwent cardiac magnetic resonance at rest and after CPT. All subjects underwent 24 hours ambulatory 3-channel electrocardiogram Holter to evaluate AD by heart rate variability. RESULTS: We did not observe any significant difference in MBF (mL/g/min) at rest and after CPT between SSc patients and healthy controls. Delta of MBF (difference between MBF after CPT and rest MBF) was lower (P = 0.039) in SSc patients than healthy controls (0.28 [0.04-0.40] vs 0.33 [0.24-0.54]). The low frequency/high frequency (LF/HF) was higher (P = 0.002) in SSc patients than healthy controls (3 [1.7-6] vs 1.8 [1.1-2.8]). The high frequencies (HF), modulated mainly by paraympathetic system, was lower (P = 0.003) in SSc patients than healthy controls (30 [16-42] vs 36.5 [24-44]). Sympathetic hyperactivity, due to reduction of parasympathetic activity (HF), is present in SSc patients. A negative correlation was observed between Delta of MBF and LF/HF (r = -0.572, P = 0.0031). CONCLUSION: AD, characterized by sympathovagal imbalance due to a reduced parasympathetic tone with high LF/HF ratio, could be responsible for the reduced myocardial vasodilatory response after CPT.

Circadian rhythm of the autonomic nervous system in insulin resistant subjects with normoglycemia, impaired fasting glycemia, impaired glucose tolerance, type 2 diabetes mellitus.

BACKGROUND: In type 2 diabetes mellitus both insulin resistance and hyperglycemia are considered responsible for autonomic dysfunction. The relation between the autonomic activity, impaired fasting glycemia and impaired glucose tolerance is, however, unclear. The purpose of this study was to evaluate and compare the circadian autonomic activity expressed as heart rate variability (HRV) measured by 24-hours ECG recording in insulin resistant subjects (IR) with characteristics as follow: IR subjects with normal oral glucose tolerance test results, IR subjects with impaired fasting glucose, IR subjects with impaired glucose tolerance and subjects with type 2 diabetes mellitus. METHODS: Eighty Caucasian insulin resistant subjects (IR) and twenty five control subjects were recruited for the study. IR subjects were divided into four groups according to the outcoming results of oral glucose tests (OGTTs): IR subjects with normal glucose regulation (NGR), IR subjects with impaired fasting glycemia (IFG), IR subjects with impaired glucose tolerance (IGT) and subjects with type 2 diabetes mellitus (DM). Autonomic nervous activity was studied by 24-hours ECG recording. Heart rate variability analysis was performed in time and frequency domains: SDNN, RMS-SD, low frequency (LF) and high frequency (HF) were calculated. RESULTS: The total SDNN showed statistically significant reduction in all four groups with insulin resistant subjects (IR) when compared to the control group (p <0,001). During night LF normalized units (n.u.) were found to be higher in all four groups including IR subjects than in the control group (all p < 0,001) and subjects with normal glucose regulation (NGR), with impaired fasting glycemia (IFG) and with impaired glucose tolerance (IGT) were found to have higher LF n.u. than those in the type 2 diabetes mellitus group. The linear regression model demonstrated direct association between LF values and the homeostasis model assessment-index (HOMA-I), in the insulin resistant group (r = 0,715, p <0,0001). CONCLUSION: The results of our study suggest that insulin resistance might cause global autonomic dysfunction which increases along with worsening glucose metabolic impairment. The analysis of sympathetic and parasympathetic components and the sympathovagal balance demonstrated an association between insulin resistance and sympathetic over-activity, especially during night. The results indicated that the sympathetic over-activity is directly correlated to the grade of insulin resistance calculated according to the HOMA-I. Since increased sympathetic activity is related to major cardiovascular accidents, early diagnosis of all insulin resistant patients should be contemplated.

Alterations of the sympathovagal balance evaluated by heart rate variability in a rare case of adult Still's disease.

We present a rare case of adult Still's disease with cardiac involvement (myocarditis and coronary arteritis). The autonomic nervous system function was evaluated by heart rate variability (HRV) analysis performed by 24-hour electrocardiographic recording during the acute phase of the disease and the remission (after 1 month and 1 year). The HRV parameters were studied in the time (standard deviation of all NN intervals-total power - SDNN, square root of the mean of the sum of the squares of the differences between adjacent NN - RMS-SD and HRV index) and frequency domains (low frequency, high frequency, and low frequency/high frequency). The results of the analysis of the HRV highlight that in the acute phase of the disease with cardiac involvement the autonomic nervous system is globally altered, with modifications of the sympathovagal balance, due to impairment of the parasympathetic component. This trend tends to persist in the short period (1 month), but seems to resolve completely within 1 year. An altered sympathovagal balance should be considered as a possible marker of vasculitis-related ischemia.

Heart rate variability in cluster headache.

Eight patients with cluster headache were studied by evaluating the heart rate variability on the basis of 24-hour ECG monitoring performed during attacks (critic periods) to demonstrate if any imbalance of the autonomic nervous system was present and to determine its temporal correlation, if any, with the attack. The same monitoring allowed us to compare the patients' data during headache-free periods (intercritic periods) with those of normal controls. Our investigation demonstrated a severe sympathovagal imbalance during spontaneous attacks: the parasympathetic drive is at once increased at the onset with a mild reduction of the sympathetic drive, and all these modifications slowly disappear at the end of each attack. Comparison of the average low-frequency and high-frequency values during intercritic periods showed a significant reduction in the low-frequency values in patients, even when the low-frequency/high-frequency ratio was normal. This is highly suggestive of the presence of an autonomic nervous system dysfunction.

Autonomic system modification in Zen practitioners.

BACKGROUND: Meditation in its various forms is a traditional exercise with a potential benefit on well-being and health. On a psychosomatic level these exercises seem to improve the salutogenetic potential in man.Especially the cardiorespiratory interaction seems to play an important role since most meditation techniques make use of special low frequency breathing patterns regardless of whether they result from a deliberate guidance of breathing or other mechanisms, for example, the recitation of specific verse. During the different exercises of Zen meditation the depth and the duration of each respiratory cycle is determined only by the process of breathing. Respiratory manoeuvres during Zazen meditation may produce HR variability changes similar to those produces during biofeedback. Recognition that the respiratory sinus arrhythmia (RSA) was mediated by efferent vagal activity acting on the sinus node led investigators to attempt to quantify the fluctuations in R-R intervals that were related to breathing. MATERIALS AND METHODS: Nine Zen practitioners with five years of experience took part in the study. Autonomic nervous system function was evaluated by heart rate variability (HRV) analysis during 24-hours ECG recording during zen meditation and at rest. RESULTS: The data of this small observational study confirm that ZaZen breathing falls within the range of low frequency HR spectral bands. Our data suggest that the modification of HR spectral power remained also in normal day when the subject have a normal breathing. CONCLUSION: We suggest that the changes in the breathing rate might modify the chemoreflex and the continuous practice in slow breathing can reduce chemoreflex. This change in the automonic control of respiration can be permanent with a resetting of endogenous circulatory rhythms.

Correlation between glycemic trends assessed by 24 h continuous monitoring and autonomic activity in patients with recent onset type 2 diabetes.

We observe, in patients with type 2 diabetes of recent onset, the activity of the autonomic nervous system and glucose metabolic impairment. The data indicate the hyperactivity of the sympathetic and minimal changes in glucose values. The role played by glycemia appeared to be less important than that represented by insulin resistance.

The correlation among QTc interval, hyperglycaemia and the impaired autonomic activity.

BACKGROUND: The QT interval reflects the duration of the intracellular action potential. Little is known on the interval QT duration in non diabetic insulin-resistant subjects. OBJECTIVE: The aims of the current study were to evaluate the QTc interval in three groups of non diabetic insulin-resistant subjects and the possible correlation between QTc and the autonomic nervous system's activity. DESIGN: 90 subjects were divided in subjects with impaired fasting glycaemia (IFG) and, by the results of OGTT, according to the criteria of ADA, in subjects with normal glucose regulation (NGR) and impaired glucose tolerance (IGT). Insulin resistance was evaluated by the homeostasis model assessment-index (HOMA-I). Heart rate variability and Qtc were calculated. RESULTS: QTc interval is correlated with SDNN, LF n.u. and LF/HF. CONCLUSION: We have observed that the QTc interval is prolonged in insulin-resistant subjects with associated impaired glucose metabolism, while no difference was reported between insulin-resistant and non insulin-resistant subjects with normal glucose regulation. We hypothesize that hyperglycaemia could play a major role than hyperinsulinemia on the QTc prolongation.

Long-term effect of liver transplantation on cirrhotic autonomic cardiac dysfunction.

There is little information on the long-term effect of liver transplantation (LT) on cardiac autonomic dysfunction in cirrhotic patients. We compared cardiac autonomic function before and in the long-term after LT. In a transversal study, we investigated 30 cirrhotics awaiting LT, 15 clinically stable patients 2-6 years after LT and 27 healthy controls. Seven cirrhotic patients were studied before LT, and 6, 12 and 33 months after LT, in a prospective fashion. Cardiac autonomic function was measured by heart rate variability (HRV) analysis during 24-h electrocardiogram recording. In the transversal study, patients with cirrhosis as compared to healthy controls had significantly reduced standard deviation of normal-to-normal RR intervals (SDNN) (p<0.001) and of the square root of the mean of squared differences between adjacent NN intervals (RMS-SD) (p<0.01), while the ratio between low frequency (LF) and high frequency (HF) at night was significantly (p<0.05) increased. Liver transplanted patients had significantly (p<0.001) higher SDNN values than cirrhotics, while RMS-SD and LF/HF at night did not differ. In the prospective study, SDNN progressively increased after LT and was significantly (p<0.05) higher at 12 and 33 months, compared to the pre-operative value. RMS-SD and LF/HF at night did not change after LT. In conclusion, the overall HRV decrease present in cirrhosis, measured by SDNN values, is partially corrected in the long-term after LT. However, parasympathetic impairment, measured by RMS-SD and LF/HF at night, is not affected even in the long-term after operation.