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The relationship between heart rate variability and prostaglandin E2 in patients with renal insufficiencies.

OBJECTIVE: To investigate the relationship between heart rate variability (HRV) and prostaglandin E2 (PGE2) in patients with renal insufficiencies. METHODS: HRV blood and 24-hour urine prostaglandin E2 (PGE2) detection were detected in the following 4 groups of people: group A was a control group comprised of 20 normal individuals; group B had 20 patients with renal disease but exhibiting normal renal function; group C contained 20 patients with renal disease and compensatory renal function; group D had 20 patients demonstrating renal insufficiencies. The indices standard deviation of all NN intervals (SDNN), index of standard deviation of the averages of NN intervals (SDANN), mean of the standard deviation of all NN intervals performed on all 5-minute segments of the entire recording (SDNNindex), square root of the mean of the sum of the squares of differences between adjacent NN intervals (rMSSD) and NN50 count divided by the total number of all NN intervals (PNN50) were used to evaluate HRV, blood and 24-hour urine were determined by specific radioimmunoassay (RIA). RESULTS: PGE2 in blood and urine and HRV exactly within 24 hours in patients with renal insufficiencies, negatively correlated with worsening damage to renal function. There was a slight or moderate correlation between blood and urine PGE2 and the SDNNindex, SDANNindex, SDNN, rMSSD and PNN50 indices (P < 0.05). CONCLUSIONS: HRV and cardiac autonomic regulatory functions are decreased in the patients with renal insufficiencies, while lower levels of PGE2 may be a related factor.

Adolescent↗

Autonomic and sensory nerve function in diabetic foot ulceration.

Peripheral sensory and autonomic nerve dysfunction are thought to be crucial factors in the pathogenesis of diabetic foot ulceration. However, their relative importance is not known. In this study we have compared peripheral sensory nerve function and cardiac autonomic reflexes in 51 diabetics with a history of foot ulceration and 480 diabetic control subjects. In the diabetics with ulceration ankle reflexes were absent or impaired and vibration perception threshold reduced in 96.1% and 82.4%, respectively, compared with 40.8% and 25.8%, respectively, in control subjects (P less than 0.001). Cardiac autonomic tests were abnormal more frequently in the diabetics with ulceration and an autonomic score derived from four tests was abnormal in 62.8% of those with ulceration compared with 13.5% of those without ulceration (P less than 0.001). Discriminant analysis of the two groups of diabetes showed that an abnormal autonomic score was the best predictor of foot ulceration in diabetic patients.

Diabetic Neuropathies↗

Non-invasive measurement of haemodynamics during sleep apnoea.

Sleep apnoeas are accompanied by large variations in heart rate (HR) and blood pressure (BP). This nocturnal variability in BP may be involved in the increased cardiovascular morbidity of these patients. Due to the complex interaction between asphyxia, intrathoracic pressure, cardiac function and autonomic activation, the exact haemodynamic mechanisms are unclear. To evaluate the components of the BP surges at resumption of breathing (RB) a non-invasive beat-to-beat measurement was taken of cardiac output (CO) by the pulse contour analysis of the Finapres signal. Six male normotensive patients, free of medication (37-60 y, BMI 26.5-43.0 kg m-2) were studied during polysomnography (apnoea index: 22-69 h-1). Systolic blood pressure rose from 126.5 +/- 1.3 mmHg at beginning apnoea (P1) to 140.4 +/- 1.3 at RB (P < 0.01, ANOVA). During sleep Stages 2 and 3, stroke volume decreased during RB to 96% of P1 value (NS). Due to an opposite change in HR, CO tended to rise at RB to 106% of P1. Computed total peripheral resistance rose during RB to 105% of P1 value (P < 0.011. Therefore, it is concluded that the surge in BP at RB after apnoea is due to concomitant increases in CO and in TPR. Both rises are presumably a consequence of sympathetic nervous activation by the arterial chemoreceptors.

Journal Article↗

Comparison of the effects of VVI versus DDD pacing on cardiac baroreflex function.

INTRODUCTION: Conventional baroreceptor-heart rate (HR) reflex sensitivity cannot be examined in chronotropically incompetent patients or in pacemaker recipients. However, cardiac baroreceptor reflex sensitivity (BRS)-stroke volume (SV), which is closely and linearly correlated with BRS-HR, may be an alternative in that population. The aim of this study was to compare the BRS-SV in pacemaker recipients with a fixed HR paced in VVI versus DDD modes in the supine and upright positions. METHODS: The pacing mode was set randomly to DDD or VVI with complete atrial and/or ventricular capture, then crossed over to the alternate mode in 9 recipients of dual-chamber pacemakers with atrioventricular (AV) block. Beat-to-beat mean blood pressure and SV were measured in the supine and upright positions, using a tilt table. The BRS-SV, expressed in %/mmHg, was the ratio of low-frequency (LF) power to total power (TP) of SV variability, measured by spectral analysis of spontaneous variations in mean blood pressure and SV. RESULTS: BRS-SV was significantly lower in the VVI than in the DDD mode in the supine (37.2 +/- 26.7 vs 14.5 +/- 7.7%/mmHg) and upright (22.9 +/- 16.9 vs 10.6 +/- 6.6%/mmHg) positions (P < 0.05 for both comparisons). CONCLUSIONS: VVI pacing is adverse from the standpoint of cardiac autonomic baroreflex function. A decreased BRS-SV may be one of the factors involved in the hemodynamic intolerance associated with VVI pacing.

Aged↗

Scintigraphic evaluation of cardiac autonomic innervation.

Alterations in cardiac autonomic neuronal function have become the focus of intense research in various cardiovascular diseases. Both single-photon emission tomography (SPECT) and the positron emission tomography (PET) imaging techniques in combination with radio-labeled neurotransmitters and receptor ligands have become available for the scintigraphic visualization of presynaptic and postsynaptic neuronal function. Several clinical studies have shown changes in tracer distribution in different clinical conditions, such as ischemic heart disease, congestive heart failure, malignant arrhythmias, heart transplantation, and in patients with diabetes. In patients with congestive heart failure, previous in vitro investigations have concentrated on the postsynaptic level of the sympathetic innervation. However, alterations in presynaptic nerve function have been demonstrated with scintigraphic investigations by decreased presynaptic tracer retention. Moreover, correlation between scintigraphic findings and clinical outcome was shown in patients with heart failure, providing important prognostic information superior to conventional risk assessment. In conclusion, scintigraphic evaluation by SPECT and PET allows functional characterization of cardiac presynaptic and postsynaptic neurons. Regional tracer uptake can be used as an index for the integrity of innervation in various diseases. Newer tracer approaches may allow the noninvasive quantification of neuronal function by PET.

Autonomic Nervous System↗

Heart rate variability in coronary artery disease.

Heart rate variability (HRV) reflects the modulation of cardiac function by autonomic and other physiological systems, and its measurement from ambulatory electrocardiograph (ECG) recordings is a useful method for both clinical and scientific purposes. Heart rate variability can be measured by several linear and non-linear methods, and various methods can give different information on neural and other physiological influences on the heart. Heart rate variability is abnormal in various settings of ischaemic heart disease, and the most important current application of HRV analysis in clinical cardiology is its measurement in postinfarction patients, in whom abnormal HRV indicates an increased risk of cardiac mortality. Future research may expand the clinical utility of HRV measurement to other clinical situations.

Coronary Disease↗

Effects of hypochlorite and hydrogen peroxide on cardiac autonomic receptors and vascular endothelial function.

1. Reactive oxygen species (ROS) are known to be involved in the progression of various cardiovascular diseases. One source of ROS is activated neutrophils, which can release superoxide anion radicals and hydrogen peroxide by membrane-bound NAD(P)H oxidases. These ROS not only destroy bacteria, but may also affect mammalian tissue. In addition, hydrogen peroxide serves as a substrate for myeloperoxidase, an enzyme that is released by activated neutrophils during inflammatory processes, as seen, for instance, in reperfusion injury and atherosclerosis. Myeloperoxidase catalyses the oxidation of chloride by hydrogen peroxide, yielding hypochlorite, an extremely potent oxidant. 2. The purpose of the present study was to evaluate the effects of hypochlorite on a variety of receptor-dependent processes in rat isolated left atria and rat thoracic aorta and to compare these results with the phenomena observed after incubation with hydrogen peroxide. 3. In the presence of hypochlorite (300 micro mol/L), the positive inotropic response of alpha1-adrenoceptor stimulation by methoxamine (300 micro mol/L) was converted into a negative inotropic response. In contrast, the positive inotropic effects of the beta1/beta2-adrenoceptor agonist isoprenaline (3 micro mol/L) and endothelin (ET)-1 (100 nmol/L) remained largely unaffected. 4. The inversion of alpha1-adrenoceptor-mediated inotropy was not obtained in the presence of hydrogen peroxide (500 micro mol/L). Hydrogen peroxide did not affect the positive inotropic response of isoprenaline, but it completely abolished the inotropic effect of ET-1. 5. The effect of cardiac M2-receptor stimulation was studied in the presence of hypochlorite and hydrogen peroxide. The negative inotropic response to acetylcholine (ACh) was significantly enhanced after hypochlorite incubation compared with control. 6. In the rat thoracic aorta, endothelial function, evaluated by means of ACh-induced vasodilation, was completely abolished in the presence of hypochlorite (100 micro mol/L), but remained unaffected by treatment with the same concentration of hydrogen peroxide. 7. From these data, we conclude that hypochlorite exerts more toxic properties than its precursor hydrogen peroxide, leading to substantial physiological alterations in cardiac and vascular tissue.

Acetylcholine↗

Does dialysis therapy improve autonomic and peripheral nervous system abnormalities in chronic uraemia?

OBJECTIVES: Autonomic nervous system (ANS) dysfunction and peripheral neuropathy occur in patients with chronic renal insufficiency. Adequate renal replacement therapy should prevent development or correct these abnormalities. DESIGN AND SUBJECTS: We studied retrospectively ANS and peripheral neuropathy in 32 patients with chronic uraemia who received either haemodialysis (16) or peritoneal dialysis (16) therapy, and compared the observed dialysis efficiency with changes in neurological function. METHODS: Heart rate variability (HRV) time domain indices and peripheral sensory nerve conduction studies were followed for a mean of 2.9 years. The adequacy of haemodialysis (HD) efficiency was estimated by Kt/V, an index of fractional urea clearance. Adequacy of continuous ambulatory peritoneal dialysis (CAPD) was estimated on the basis of the patient's wellbeing and nutritional status as excellent, satisfactory or poor. Based on observed changes in HRV time domain measures, the observations were divided in three subgroups: improved, unchanged or deteriorated. RESULTS: The peripheral sensory nerve conduction studies were abnormal in 38% of the patients and did not change significantly during the study. Improvement in HRV time domain measures occurred in HD patients with mean Kt/V > 1.20 or in CAPD patients with satisfactory or excellent response to dialysis treatment. Values of Kt/V < 0.85 in HD patients were associated with progressive deterioration of autonomic neuropathy. Diabetic patients (n = 4) differed from others as their HRV was grossly abnormal and did not improve. CONCLUSIONS: The adequacy of haemodialysis is a predictor of improvement of cardiac autonomic nervous function in chronic uraemia. The same trend of improvement was seen also in CAPD patients.

Autonomic Nervous System Diseases↗

Autonomic function in type I diabetes mellitus complicated by nephropathy. A cross-sectional analysis in the presymptomatic phase.

The purpose of this study was to determine the prevalence of parasympathetic and sympathetic autonomic dysfunction in long-standing type I diabetics with established nephropathy and to correlate autonomic function with cardiac risk factors. We used prospective analysis of heart rate variations to standardized testing and 24-hour blood pressure control prior to enrollment in a study utilizing various methods of intense diabetic control to prevent deterioration of kidney function. The settings were outpatient clinical research units. The patients were 42 type I diabetics with proteinuria (total urinary protein > or = 300 mg/day or urinary albumin > or = 100 mg/day) and creatinine clearance > or = 30 mL/min. Heart rate variation during respiratory cycles with change in posture from supine to upright, and during the Valsalva maneuver was recorded by a computerized method. Mean arterial blood pressure was recorded for 24 h by a computerized method. Heart rate variations in this group were abnormal during timed respiratory cycles in 26 of 40 patients (56%), during changes in posture in 15 of 40 patients (38%), and during Valsalva maneuver in 13 of 34 patients (38%) whose retinal disease permitted Valsalva testing. Blunted day/night mean arterial pressure ratios occurred in 18 of 41 (44%) patients and were more severe in men than in women (1.00 v 1.06, P < or = .05). Absence of deep tendon reflexes was associated with an increased incidence of both parasympathetic (respiratory rate variation) and sympathetic (postural rate variation) abnormalities (both P < or = .05). Loss of vibration sensation was not associated with autonomic functional abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Blood pressure and heart rate regulation in diabetics].

Cardiac autonomic neuropathy (CAN) is frequent in subclinical stages. Its prognostic value has been demonstrated. Cardiac autonomic neuropathy induces different functional cardiac changes, especially a reduction in left ventricular contractility and changes in ventricular repolarisation. It is also associated with changes in the daily variations in blood pressure. The association of CAN and silent myocardial ischaemia significantly worsens the prognosis. The investigation of CAN in the greatest number of diabetic patients is therefore justified. The study of heart rate variations during deep respiration, active orthostatism or Valsalva manoeuvre, is still the reference. This method is simple, reproducible and may be carried out in the clinical setting in 10 to 15 minutes. The results must be strictly interpreted with rigour with respect to age. Orthostatic hypotension is a late sign of sympathetic nervous system disease. Spectral analysis of blood pressure variations on orthostatism or the study of cutaneous blood flow during activating the sympathetic system tests of greater sensitivity, should be developed. The demonstration of subclinical CAN should lead to the careful use of drugs which may induce orthostatic hypotension and certain antiarrhythmics, to search for disorders of ventricular repolarisation and for silent myocardial ischaemia in diabetics with several risk factors.

Adolescent↗

The peripheral pulse wave: information overlooked.

although the waveform derived from a peripheral pulse monitor or pulse oximeter may resemble an arterial pressure waveform, it is in fact a visualization of blood volume change in transilluminated tissue caused by passage of blood: an indication of perfusion or blood flow. Most currently available pulse oximeters indicate this flow, but few display it in usable form. Since adequate tissue blood flow is a prerequisite for normal metabolic activity, it is a parameter that should merit a place in standard anesthesia or intensive care monitors. That the peripheral tissue blood flow is not routinely displayed may be in part due to the difficulty in quantifying data obtained: flow is not accurately measured as simply as pressure, even by invasive means. It is in the pattern of the waveform that beat-to-beat changes in stroke volume can be better seen than measured, or in the interaction of ventilation and circulation that tests general circulatory performance. The origin and interpretation of these changes are discussed and illustrated with examples. We indicate how new physiological tests of autonomic function and cardiac preload can be developed using pulse plethysmography. The importance and application of the Valsalva effect on the waveform is emphasized. This effect is particularly applicable for monitoring adequate fluid loading and the action of vasodilator drugs, which are both important in anesthesia. Differences between the arterial pulse pressure wave and tissue flow wave are discussed, as well as the cause of certain artifacts, including the wandering dicrotic notch.

Anesthesia↗

Auditory brainstem latencies in type I (insulin-dependent) diabetic patients.

INTRODUCTION: This study was undertaken to compare auditory brainstem response latencies in insulin-dependent diabetics, and to compare these findings with metabolic control, microangiopathy, neuropathy, and the duration of diabetes. METHODS: Auditory brainstem latencies were studied in 53 type I diabetic patients and 42 randomly selected nondiabetic control subjects, aged between 20 and 40 years. Three different stimulus repetition rates (10, 30, and 50 Hz) were used. All subjects had normal hearing ability. RESULTS: Wave V latencies were longer in diabetic patients when compared with those of control subjects at all repetition rates. At repetition rates of 10 and 50 Hz, diabetic patients had a prolonged I-V interwave latency, and at a repetition rate of 50 Hz, diabetics had a longer III-V interwave latency than control subjects. These findings indicate a central disturbance in the auditory pathway. Microvascular complications (retinopathy, nephropathy) and the duration of diabetes were associated with the prolongation of auditory brainstem latencies. In contrast, poor metabolic control (high fasting blood glucose and glycated hemoglobin A1c) at the time of the present study was only marginally associated with prolonged auditory brainstem latencies. The changes in auditory brainstem latencies associated with diabetic neuropathy (measured with five cardiac autonomic nervous function tests) appeared simultaneously with microvascular complications and in patients with diabetes of long duration, and thus a causative role of diabetic neuropathy in the pathogenesis of prolonged auditory brainstem latencies remains unsolved. CONCLUSION: Delayed auditory brainstem latencies in type I diabetic patients are probably caused by the long duration of diabetes and the microvascular complications associated with it.

Adult↗

Regular physical exercise, heart rate variability and turbulence in a 6-year randomized controlled trial in middle-aged men: the DNASCO study.

HRV and HRT are independent predictors of cardiovascular mortality. Aging reduces HRV, but results from the physical exercise trials are controversial. The primary aim was to study changes in heart rate variability (HRV) and heart rate turbulence (HRT) in a six-year controlled randomized trial at regular low to moderate intensity physical exercise. One hundred forty men aged 53--63 years were randomized in to an exercise or a control groups. The participants underwent a maximal bicycle ergometer exercise test with respiratory gas analyses annually for six years. At baseline and after intervention, 24-h ambulatory ECG registrations were performed to assess HRV (n=100). HRT was determined among subjects with single ventricular premature complexes (VPC) (n=73). In the exercise group, ventilatory aerobic threshold (VAT) increased by 16% indicating enhanced submaximal cardiorespiratory fitness. No significant differences were found in any of the HRV or HRT parameters between the groups. However, the observed increase in VAT correlated significantly with the improvement in HRV parameters. The change in turbulence slope (TS) correlated with the changes in most HRV variables and the change in turbulence onset (TO) correlated with the changes in three frequency domain parameters. Our results suggest that in addition to improvement in submaximal cardiorespiratory fitness, regular low to moderate intensity physical exercise seems to have beneficial effects also on cardiac autonomic nervous function, a clinically relevant predictor of cardiovascular morbidity and mortality.

Anaerobic Threshold↗

Proinsulin C-peptide activates vagus efferent output in rats.

The aim of this study was to examine the effect of proinsulin C-peptide on the autonomic nervous systems in rats. Intravenous administration of C-peptide gradually increased electrophysiological activity of the vagus nerves into the stomach and pancreas for at least 90 min. It also slightly increased gastric acid secretion that was suppressed by the treatment with atropine. Intraperitoneal injection of C-peptide did not affect the basal and stress-induced norepinephrine (NE) turnover rate, a biochemical index of sympathetic nerve activity. These results indicate that C-peptide increases parasympathetic nerve activity without affecting sympathetic nerve activity. This could explain, at least in part, the ameliorating effects of C-peptide on impaired cardiac autonomic nerve functions in patients with type 1 diabetes.

Animals↗

Effects of endurance training on heart rate and blood pressure variability.

PURPOSE: To study the influences of a 1-year controlled, randomized endurance exercise training period on heart rate (HR) and blood pressure variability in a representative sample of Finnish men in their late middle age. METHODS AND RESULTS: Subjects were 140 sedentary men aged 53-63 years. The men were randomized into two identical groups: an intervention (EX) and a reference (CO) group. One hundred and twelve of them remained in the final analysis (EX: n=59, CO: n=53). EX trained for 30-60 min three to five times a week with the intensity of 40-60% of maximal oxygen consumption. In EX, 1 year of regular exercise training increased oxygen consumption at respiratory compensation threshold by 11% (P < or = 0.001) in a maximal cardiorespiratory test. Total power and very low frequency power of R-R interval variability (ms2) tended to increase in the EX group by 26 and 42% and to decrease in the CO group by 13 and 10% (interaction P<0.05 and P<0.01), respectively. There were no significant changes in blood pressure variability. CONCLUSION: Regular low- to moderate-intensity exercise training could retard the declining tendency in cardiac autonomic nervous function in older men during 1 year.

Autonomic Nervous System↗

Effect of cold exposure on older humans.

Epidemiological studies have shown excess winter mortality particularly in older age groups. A question is how much these statistics are affected by age-related physiological changes in cold thermoregulation and how much due to other factors related to aging. In experimental studies concerning age and cold stress both whole-body and local exposures have been used mostly in resting subjects with minimal clothing. Older persons, particularly men over ca. 60 years, are less able to maintain core temperature during a given cold challenge compared to younger individuals. Older persons have a reduced cutaneous thermal sensitivity, and a reduced subjective thermal perception during cooling. Thus, older people may require a more intense stimulus to perform protective actions against cold stress. Older persons' skin vasoconstrictive response to cold is diminished compared to younger persons, which seems partly related to a reduced skin vasomotor sensitivity to sympathoneuronal stimuli. The cold-induced rise in metabolic rate is attenuated in older persons, but the mechanism is unknown. Both central and peripheral components seem to be involved in the age-related changes in regulatory effector functions. Enhanced aerobic fitness may not give added protection against core cooling during cold stress in the elderly, but seems to attenuate older subjects' heightened blood pressure response to cold. Bronchial responsiveness to face cooling may increase with age. Further studies are needed to examine the age-related changes in non-thermoregulatory responses to cold (e. g. hemodynamics, cardiac function, respiration, autonomic nervous function), and the modifying effects of acute exercise and physical training.

Aged↗

Effects of Korean traditional herbal remedy on heart rate variability: linear and nonlinear analysis.

Heart rate variability was compared in 20 subjects taking traditional herbal remedy (Ondamtanggamibang) or placebo control pill, in placebo controlled design experiment. Herbal remedy group reported more pleasant and clam emotions than did the placebo group. Herbal remedy reduced the heart rate and increased heart rate variability (HRV) as indicated by a reduced low frequency/high frequency power ratio of heart rate variability. With nonlinear analysis, the Poincaré plot index of HRV and approximate entropy was greater in the herbal remedy group than in the control group. These findings suggest that herbal remedy stabilizes the sympathovagal function and cardiac autonomic nervous system by inducing more positive emotions than does placebo therapy. In conclusion, herbal remedy may act by stabilizing both the autonomic nervous system and the emotional state.

Adult↗

The effects of postural changes of baroreflex gain in normal and hypertensive pregnancies.

In order to understand the changes of baroreflex gain due to postural changes in normal pregnancies, we measured percentage changes (% changes) in blood pressure (SBP, DBP), heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) as well as cardiac autonomic nervous function (HF as an index of parasympathetic and LF/HF as an index of sympathetic function) and compared these parameters in normal pregnancies with those found in hypertensive pregnancies, such as chronic hypertensive (CHP) and severe preeclamptic pregnancies (PE), in late pregnancy (after 32 wks). When the position was changed from supine to standing in normal and non-pregnant women, the % changes of HR, DBP, TPR and LF/HF were increased and SBP, SV, CO and HF were decreased. The % changes of these parameters, however, were gradually decreased as pregnancy progressed, especially after 20-24 wks of gestation. In hypertensive pregnancies, however, even in late pregnancy, the decreased SBP and increased TPR was still observed and the profound decrease of CO and SV and increase of TPR were characteristic in PE when compared to CHP.

Adult↗