Neural control of cardiovascular function in black adults: implications for racial differences in autonomic regulation.

Black adults are at increased risk for developing hypertension and cardiovascular and chronic kidney disease and have greater associated morbidity/mortality than white adults who are otherwise demographically similar. Despite the key role of the autonomic nervous system in the regulation of cardiovascular function, the mechanistic contributions of sympathetic nerves to racial differences in cardiovascular dysfunction and disease remain poorly understood. In this review, we present an update and synthesis of current understanding regarding the roles of autonomic neural mechanisms in normal and pathophysiological cardiovascular control in black and white adults. At rest, many hemodynamic and autonomic variables, including blood pressure, cardiac output, and sympathetic nerve activity, are similar in healthy black and white adults. However, resting sympathetic vascular transduction and carotid baroreflex responses are altered in ways that tend to promote increased vasoconstriction and higher blood pressure, even in healthy, normotensive black adults. Acute sympathoexcitatory maneuvers, including exercise and cold pressor test, often result in augmented sympathetic and hemodynamic responses in healthy black adults. Clinically, although mechanistic evidence is scarce in this area, existing data support the idea that excessive sympathetic activation and/or transduction into peripheral vasoconstriction contribute importantly to the pathophysiology of hypertension and chronic kidney disease in black compared with white adults. Important areas for future work include more detailed study of sympathetic and hemodynamic reactivity to exercise and other stressors in male and female black adults and, particularly, sympathetic control of renal function, an important area of clinical concern in black patients.

Sex Differences in Regulation of Blood Pressure.

Hypertension is one of the leading risk factors for cardiovascular disease, myocardial infarction, and stroke. There are gender differences in the prevalence of hypertension and in the mechanisms responsible for hypertension in humans. This review will discuss the mechanisms for regulation of blood pressure, sex differences that have been identified in animal studies, and the gender differences that have been identified in humans.

Sex-Specific Physiology and Cardiovascular Disease.

Sex differences in cardiovascular diseases can be classified as those which are specific to one sex and those that differ in incidence, prevalence, etiology, symptomatology, response to treatment, morbidity, and mortality in one sex compared to the other. All sex differences in cardiovascular conditions have their basis in the combined expression of genetic and hormonal differences between women and men. This chapter addresses how understanding basic mechanisms of hormone responses, imaging diagnostics, and integration of genomics and proteomics has advanced diagnosis and improved outcomes for cardiovascular conditions, apart from those related to pregnancy that are more prevalent in women. These conditions include obstructive coronary artery disease, coronary microvascular dysfunction, spontaneous coronary artery dissection, diseases of the cardiac muscle including heart failure and takotsubo cardiomyopathy, and conditions related to neurovascular dysregulation including hot flashes and night sweats associated with menopause and effects of exogenous hormones on vascular function. Improvement in technologies allowing for noninvasive assessment of neuronally mediated vascular reactivity will further improve our understanding of the basic etiology of the neurovascular disorders. Consideration of sex, hormonal status, and pregnancy history in diagnosis and treatment protocols will improve prevention and outcomes of cardiovascular disease in women as they age.

Assessment of effects of differences in trunk posture during Fowler's position on hemodynamics and cardiovascular regulation in older and younger subjects.

BACKGROUND: Downward shifts in blood volume with changing position generally cause tachycardic responses. Age-related decreases in vagal nerve activity could contribute to orthostatic hypotension in older individuals. Fowler's position is a reclined position with the back between 30° and 60°, used to facilitate breathing, eating, and other routine daily activities in frail and elderly patients. OBJECTIVE: This study examined whether stroke volume (SV) was higher and heart rate (HR) lower in Fowler's position with an upright upper trunk than in Fowler's position with the whole trunk upright in both older and younger subjects, based on the assumption that lower HR would result from reduced sympathetic activation in older individuals. METHODS: We assessed hemodynamics and HR variability from electrocardiography, noninvasive arterial pressure and impedance cardiography in 11 younger male subjects (age range, 20-22 years) and 11 older male subjects (age range, 64-79 years), using three positions: supine, or Fowler's positions with either 30° of lower trunk inclination and 60° of upper trunk inclination (UT60) or 60° of whole trunk inclination (WT60). Comparisons were then made between age groups and between positions. RESULTS: Reductions in SV and tachycardic response were smaller with UT60 than with WT60, in both younger and older subjects. In addition, reduced tachycardic response with upright upper trunk appeared attributable to decreased vagal withdrawal in younger subjects and to reduced sympathetic activation in older subjects. CONCLUSION: Our findings indicate that an upright upper trunk during Fowler's position allowed maintenance of SV and inhibited tachycardic response compared to an upright whole trunk regardless of age, although the autonomic mechanisms underlying tachycardic responses differed between younger and older adults. An upright upper trunk in Fowler's position might help to reduce orthostatic stress and facilitate routine activities and conversation in frail patients.

Role of leptin in energy expenditure: the hypothalamic perspective.

The adipocyte-derived hormone leptin is a peripheral signal that informs the brain about the metabolic status of an organism. Although traditionally viewed as an appetite-suppressing hormone, studies in the past decade have highlighted the role of leptin in energy expenditure. Leptin has been shown to increase energy expenditure in particular through its effects on the cardiovascular system and brown adipose tissue (BAT) thermogenesis via the hypothalamus. The current review summarizes the role of leptin signaling in various hypothalamic nuclei and its effects on the sympathetic nervous system to influence blood pressure, heart rate, and BAT thermogenesis. Specifically, the role of leptin signaling on three different hypothalamic nuclei, the dorsomedial hypothalamus, the ventromedial hypothalamus, and the arcuate nucleus, is reviewed. It is known that all of these brain regions influence the sympathetic nervous system activity and thereby regulate BAT thermogenesis and the cardiovascular system. Thus the current work focuses on how leptin signaling in specific neuronal populations within these hypothalamic nuclei influences certain aspects of energy expenditure.

Why Not to Use the Handgrip Test in the Assessment of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes Mellitus?

OBJECTIVE: Historically, a set of 5 Cardiovascular Autonomic Reflex Tests (CARTs) were considered to be the gold standard in the assessment of Cardiovascular Autonomic Neuropathy (CAN). However, measuring diastolic Blood Pressure (BP) response to sustained handgrip is omitted in recent guidelines. We aimed to assess the association between the handgrip and the other 4 tests as well as to identify determinants of the handgrip test results in diabetic patients. PATIENTS AND METHODS: 353 patients with diabetes (DM) were recruited (age: 60.2±7.4 years; female: 57.2%; BMI: 29.3±2.1 kg/m2; DM duration: 15.6±9.9 years; HbA1c: 7.8±1.4% (66 mmol/mol); with type 1 DM: 18.1%). CAN was assessed by 5 CARTs: the deep breathing test, Valsalva ratio, 30/15 ratio, handgrip and orthostatic hypotension test. RESULTS: Sensitivity and specificity of the handgrip test in the diagnosis of definite CAN were 24.6% (95%CI 17.7-33.1%) and 79.4% (95%CI 73.3-84.4%), respectively. Results of the handgrip test did not show any association with those of the deep-breathing test (y=0.004, p=0.563), 30/15 ratio (y=0.282, p=0.357), Valsalva ratio (y=-0.058, p=0.436) and orthostatic hypotension (y=-0.026, p=0.833). Handgrip test abnormality showed an independent association with higher initial diastolic BP (OR 1.05, p=0.0009) and an independent inverse association with the presence of hypertension (OR=0.42, p=0.006). CONCLUSION: Our data confirm that the handgrip test should no longer be part of the cardiovascular autonomic testing being highly dependent on hypertensive status and baseline diastolic BP. Exaggerated exercise pressor response is proposed as putative mechanism for the inverse association between abnormal results of the handgrip test and hypertension. Adequate CARTs are important to allow their use in clinical trials and for the prevention of DM-associated complications by initiating early treatment.

Neurophysiological assessment of sympathetic cardiovascular activity after loss of postganglionic neurons in the anesthetized rat.

The goal of this study was to determine the degree of sympathetic postganglionic neuronal loss required to impair cardiovascular-related sympathetic activity. To produce neuronal loss separate groups of rats were treated daily with guanethidine for either 5days or 11days, followed by a recovery period. Sympathetic activity was measured by renal sympathetic nerve activity (RSNA). Stereology of thoracic (T13) ganglia was performed to determine neuronal loss. Despite loss of more than two thirds of neurons in T13 ganglia in both treated groups no effect on resting blood pressure (BP) or heart rate (HR) was detected. Basal RSNA in rats treated for 5days (0.61±0.10µV∗s) and 11days (0.37±0.08µV∗s) was significantly less than vehicle-treated rats (0.99±0.13µV∗s, p<0.05). Increases in RSNA by baroreceptor unloading were significantly lower in 5-day (1.09±0.19µV∗s) and 11-day treated rats (0.59±0.11µV∗s) compared with vehicle-treated rats (1.82±0.19µV∗s, p<0.05). Increases in RSNA to chemoreceptor stimulation were significantly lower in 5-day treated rats (1.54±0.25µV∗s) compared with vehicle-treated rats (2.69±0.23µV∗s, p<0.05). Increases in RSNA in 11-day treated rats were significantly lower (0.75±0.15µV∗s, p<0.05) compared with both vehicle-treated and 5-day treated rats. A positive correlation of neurons to sympathetic responsiveness but not basal activity was detected. These data suggest that diminished capacity for reflex sympathetic responsiveness rather than basal activity alone must be assessed for complete detection of neurophysiological cardiovascular impairment.

A comprehensive assessment of cardiovascular autonomic control using photoplethysmograms recorded from the earlobe and fingers.

We compare the spectral indices of photoplethysmogram variability (PPGV) estimated using photoplethysmograms recorded from the earlobe and the middle fingers of the right and left hand and analyze their correlation with similar indices of heart rate variability (HRV) in 30 healthy subjects (26 men) aged 27 (25, 29) years (median with inter-quartile ranges) at rest and under the head-up tilt test. The following spectral indices of PPGV and HRV were compared: mean heart rate (HR), total spectral power (TP), high-frequency (HF) and low-frequency (LF) ranges of TP in percents (HF% and LF%), LF/HF ratio, and spectral coherence. We assess also the index S of synchronization between the LF oscillations in HRV and PPGV. The constancy of blood pressure (BP) and moderate increase of HR under the tilt test indicate the presence of fast processes of cardiovascular adaptation with the increase of the sympathetic activity in studied healthy subjects. The impact of respiration on the PPGV spectrum (accessed by HF%) is less than on the HRV spectrum. It is shown that the proportion of sympathetic vascular activity (accessed by LF%) is constant in the PPGV of three analyzed PPGs during the tilt test. The PPGV for the ear PPG was less vulnerable to breathing influence accessed by HF% (independently from body position) than for PPGs from fingers. We reveal the increase of index S under the tilt test indicating the activation of interaction between the heart and distal vessels. The PPGV spectra for finger PPGs from different hands are highly coherent, but differ substantially from the PPGV spectrum for the ear PPG. We conclude that joint analysis of frequency components of PPGV (for the earlobe and finger PPGs of both hands) and HRV and assessment of their synchronization provide additional information about cardiovascular autonomic control.

Assessment of the relationship between hypoglycaemia awareness and autonomic function following islet cell/pancreas transplantation.

BACKGROUND: This study assesses the autonomic function of patients who have regained awareness of hypoglycaemia following islet cell or whole pancreas transplant. METHODS: Five patients with type 1 diabetes and either islet cell (four patients) or whole pancreas (one patient) transplant were assessed. These patients were age-matched and gender-matched to five patients with type 1 diabetes without transplant and preserved hypoglycaemia awareness and five healthy control participants without diabetes. All participants underwent (i) a battery of five cardiovascular autonomic function tests, (ii) quantitative sudomotor axonal reflex testing, and (iii) sympathetic skin response testing. RESULTS: Total recorded hypoglycaemia episodes per month fell from 76 pre-transplant to 13 at 0- to 3-month post-transplant (83% reduction). The percentage of hypoglycaemia episodes that patients were unaware of decreased from 97 to 69% at 0-3 months (p < 0.001, Fisher's exact test) and to 20% after 12 months (p < 0.0001, Fisher's exact test). This amelioration was maintained at the time of testing (mean time: 4.1 years later, range: 2-6 years). Presence of significant autonomic neuropathy was seen in all five transplanted patients (at least 2/3 above modalities abnormal) but in only one of the patients with diabetes without transplantation. CONCLUSIONS: The long-term maintenance of hypoglycaemia awareness that returns after islet cell/pancreas transplantation in patients with diabetes is not prevented by significant autonomic neuropathy and is better accounted for by other factors such as reversal of hypoglycaemia-associated autonomic failure.

Assessment of cardiovascular autonomic function in patients with polycystic ovary syndrome.

AIM: The study was conducted to assess the sympathovagal balance in patients with polycystic ovary syndrome (PCOS) using short-term heart rate variability (HRV) analysis and conventional autonomic function tests (CAFT). METHODS: Thirty-one newly diagnosed patients with PCOS and 30 age-matched controls were recruited. Body mass index (BMI), waist : hip ratio (WHR), cardiovascular parameters such as basal heart rate (BHR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and rate-pressure product (RPP), and fasting blood glucose (FBG) were measured in both groups. Cardiovascular autonomic functions assessed were spectral analysis of HRV, heart rate and blood pressure response to standing (30:15 ratio), deep breathing (E:I ratio) and isometric handgrip (ΔDBP(ihg)). RESULTS: The cases had significantly increased BMI, WHR, BHR, SBP, DBP and RPP. Ratio of low-frequency to high-frequency power of HRV (LF-HF ratio), the marker of sympathovagal balance was significantly increased in cases compared to controls. Time-domain indices of HRV and E:I ratio were decreased, and 30:15 ratio, ΔDBP(ihg) and FBG were increased in cases. Though there was a significant correlation of LF-HF ratio with BMI, WHR, BHR, RPP and FBG, only BHR and RPP had independent contribution to LF-HF ratio. CONCLUSION: We conclude that PCOS patients have altered autonomic modulation in the form of increased sympathetic and decreased parasympathetic reactivity and HRV. The sympathovagal imbalance exposes them to cardiovascular morbidities.

In vivo assessment of neurocardiovascular regulation in the mouse: principles, progress, and prospects.

A growing body of evidence indicates that a number of common complex diseases, including hypertension, heart failure, and obesity, are characterized by alterations in central neurocardiovascular regulation. However, our understanding of how changes within the central nervous system contribute to the development and progression of these and other diseases remains unclear. As with many areas of cardiovascular research, the mouse has emerged as a key species for investigations of neuroregulatory processes because of its amenability to highly specific genetic manipulations. In parallel with the development of increasingly sophisticated murine models has come the miniaturization and advancement in methodologies for in vivo assessment of neurocardiovascular end points in the mouse. The following brief review will focus on a number of key direct and indirect experimental approaches currently in use, including measurement of arterial blood pressure, assessment of cardiovascular autonomic control, and evaluation of arterial baroreflex function. The advantages and limitations of each methodology are highlighted to allow for a critical evaluation by the reader when considering these approaches.

Longitudinal assessment of the effects of oestrogen on blood pressure and cardiovascular autonomic activity in female rats.

1. Published data concerning the effects of ovarian hormones on haemodynamic variability are contradictory. For the first time, the present study used radiotelemetric haemodynamic monitoring to investigate the long-term effects of chronic oestrogen depletion and repletion on cardiovascular autonomic control and arterial baroreflex sensitivity (BRS) in female rats. 2. Blood pressure (BP), heart rate (HR) and +dP/dt(max) of arterial pressure (an estimate of myocardial contractility) were monitored in sham-operated (SO), ovariectomized (OVX) and oestrogen-replaced OVX rats (OVXE2) for 16 weeks. Cardiovascular autonomic control and baroreflexes were assessed by frequency domain analysis of interbeat intervals (IBI) and systolic BP (SBP). 3. Compared with SO rats, OVX rats exhibited no changes in BP, short-lived decreases in HR and sustained reductions in +dP/dt(max) of arterial pressure. The high- (HF; 0.75-3 Hz) and low-frequency (LF; 0.25-0.75 Hz) components of spectral power of IBI were significantly decreased and increased, respectively, by ovariectomy. An increase in the IBI(LF/HF) ratio in OVX rats suggests a shift in the cardiac sympathovagal balance towards sympathetic dominance. Index alpha, the spectral index of spontaneous BRS, was reduced by OVX. 4. Oestrogen replacement caused significant reductions in BP and HR and reversed OVX-induced changes in +dP/dt(max) of arterial pressure and cardiac autonomic activity. The LF oscillations of SBP were reduced in OVXE2 rats, suggesting a reduction in vascular sympathetic tone by oestrogen. 5. These findings highlight the importance of long-term oestrogen therapy in rectifying the detrimental effects of depletion of ovarian hormones on the cardiovascular system and baroreflex.

Cardiovascular costs of emotion suppression cross ethnic lines.

Previous research has shown that inhibiting emotion-expressive behavior (emotion suppression) leads to increased sympathetic activation of the cardiovascular system [Gross, J.J. and Levenson, R.W. (1993). Emotional suppression: physiology, self-report, and expressive behavior. J. Pers. Soc. Psychol. 64(6), 970-986]. Ethnic differences have been reported in how frequently suppression is used as an emotion regulation strategy [Gross, J.J. and John, O. (2003). Individual differences in two emotion regulation processes: implications for affect, relationships, and well-being. J. Pers. Soc. Psychol. 85(2), 348-362]; however, it remains unknown whether there are ethnic differences in the physiological consequences of suppression. To test this, 168 participants from four ethnic groups (African American, Chinese American, European American, Mexican American) watched a disgust-eliciting film clip; half were instructed to suppress their emotions and half simply watched the film. Consistent with previous research, suppression was associated with decreased facial behavior, increased cardiovascular activation, and no impact on subjective emotional experience. Ethnicity failed to moderate these effects, indicating the generality of the cardiovascular consequences of emotion suppression across ethnic background.

Non-invasive assessment of cardioregulatory autonomic functions in children with epilepsy.

OBJECTIVES: We aimed to evaluate the interictal cardiovascular autonomic functions in pediatric patients with idiopathic epilepsy, both partial and generalized. MATERIALS AND METHODS: The study included 25 patients with idiopathic epilepsy and 50 control subjects. Patients underwent five standardized clinical cardiovascular reflex autonomic tests [resting heart rate (HR), HR response to deep breathing and to Valsalva maneuver, the 30:15 ratio of HR response to standing, and blood pressure response to standing], as well as a 12 lead surface electrocardiogram. Heart rate variability (HRV) was tested via 24-h Holter monitoring and the time domain parameters (SDNN, PNN50, rMSDD) were assessed. Excretion of vanillyl mandelic acid and metanephrine was measured in 24-h urine collection. RESULTS: Clinical reflex autonomic tests showed mild dysfunction in 8%, moderate dysfunction in 44% and severe dysfunction in 4% of patients. The HRV parameter, SDNN, was reduced in all age groups, while rMSDD and PNN50 were reduced only in the older age group. Metanephrine levels were significantly reduced in the patients group. Patients with uncontrolled epilepsy had a significantly higher frequency of autonomic dysfunction as assessed by clinical scoring. CONCLUSION: Cardiac autonomic dysfunction is not uncommon in pediatric patients with epilepsy. Altered cardiovascular regulation seems to be related to the epilepsy itself rather than to the characteristics of the disorder.

Serial assessment of cardiovascular control shows early signs of developing pre-eclampsia.

PURPOSE: To evaluate whether differences in autonomic cardiovascular control between normal pregnant women and women who develop pre-eclampsia later in pregnancy can be detected even before or early in pregnancy. DESIGN: We studied 42 women, 21 multigravid with a history of pre-eclampsia and 21 primigravid, before pregnancy, at 6, 8, 12, 16, 20 and 32 weeks gestation and 15 weeks after delivery. METHODS: The outcome of pregnancy was classified after delivery as normal pregnancy (NP group) or pre-eclampsia (PE group). Continuous heart rate and blood pressure were recorded by Portapres (TNO, Amsterdam, The Netherlands) during orthostatic stress, during rest in a supine and sitting position, and during paced breathing for periods of 1 min at breathing frequencies of 6, 10 and 15 breaths/min. Baroreflex gain from heart rate and blood pressure variability and the phase angle between both signals at low (approximately 0.1 Hz) and high frequency (respiratory rate) were analyzed by spectral analysis. RESULTS: Eight women were diagnosed with pre-eclampsia. Subgroups did not differ in age, weight or height. The PE group showed a significantly higher mean arterial pressure before and during pregnancy [analysis of variance (ANOVA), P = 0.001], a significantly larger initial blood pressure drop to orthostatic stress before and in the first half of pregnancy (ANOVA, P = 0.002) and a significantly larger negative phase difference during supine rest at low frequency from 8 weeks onward (ANOVA P = 0.003). CONCLUSIONS: These findings are compatible with increased resting sympathetic activity and decreased circulating volume, already present before and early in pregnancy, in women who will later develop pre-eclampsia.

[Diagnostic evaluation of cardiovascular autonomic function in patients with diabetes mellitus]. / Valoración diagnóstica de la función autónoma cardiovascular en el paciente con diabetes mellitus.

Cardiovascular autonomic neuropathy is a common complication of diabetes mellitus. There are several diagnostic methods currently used. New techniques are described. The purpose of this review paper is to describe and analyze the clinical relevance of all this methods and propose an algorithm for the diagnosis of the cardiovascular autonomic neuropathy at daily medical practice.

Non-invasive assessment of autonomic cardiovascular control in normal human pregnancy and pregnancy- associated hypertensive disorders: a review.

PURPOSE: Pre-eclampsia is a major complication of pregnancy. Although the disorder usually becomes apparent only in the third trimester of pregnancy, evidence is available that underlying pathophysiological abnormalities are already present early in pregnancy. The association between alterations in autonomic cardiovascular control and the development of hypertension in pregnancy has been investigated for some time. Non-invasive methods are especially of interest, since they have the advantage of minimal risk for the mother and the conceptus and enable repeated measurements during pregnancy. If non-invasive tests for autonomic cardiovascular control could demonstrate the increased sympathetic activity, as observed by microneurography than this method is a candidate for early identification of pre-eclampsia. Therefore, the literature on non-invasive testing of autonomic cardiovascular control in normal pregnancies and pre-eclampsia was summarized. DATA IDENTIFICATION AND SELECTION: Medline was searched and 36 articles on autonomic cardiovascular control in human pregnancy by non-invasive test methods were reviewed. For each test method, data of different studies were summarized to evaluate if the method could discriminate between healthy pregnancy and pre-eclampsia. CONCLUSION: Although small differences have been observed between normal pregnancy and pre-eclampsia in individual studies using non-invasive methods, the consistency in the available data is insufficient to discriminate between normal pregnancy and pre-eclampsia. The failure to demonstrate the increased sympathetic activity, as observed by direct microneurography, might be due to methodological factors of the non-invasive studies. Alternatively, sympathetic activity to resistance vessels in skeletal muscle may not be a proper reflection of autonomic cardiovascular control in pregnancy. Well-designed longitudinal research could be useful to test these suppositions.

Assessment of cardiovascular autonomic dysfunction in multiple system atrophy.

Because heart rate is controlled mainly by the autonomic nervous system, cardiovascular autonomic dysfunction may contribute to the prognosis of patients with multiple system atrophy (MSA). To clarify cardiovascular autonomic dysfunctions in MSA, the authors investigated the relation between blood pressure (BP) and pulse rate (PR), and assessed a power spectral analysis of heart rate variability (HRV) during the clinical course using ambulatory BP and a heart rate monitor for 24 hours. The authors studied seven patients with MSA (five men and two women, aged 61.0 +/- 5.8 years) and seven healthy volunteers (four men and three women, aged 58.0 +/- 6.6 years) without hypertension, heart disease, or intracranial lesions. The MSA group showed abnormal circadian variations of BP and PR and a significantly decreased correlation coefficient between BP and PR. A significant decrease and altered circadian variation also existed in the number of changes in successive R-R intervals greater than 50 msec (RR50) and in the power of the high- and low-frequency component of HRV. The authors observed a significant negative correlation between the duration of illness and the number of changes in successive R-R intervals greater than 50 msec. The characteristic dysautonomia in MSA was a decrease in sympathetic and parasympathetic activity, with an abnormal circadian rhythm of BP and HRV. The balance between sympathetic and parasympathetic activity was also impaired. The parasympathetic modulation represented by RR50 worsened according to the development of the illness. Those autonomic dysfunctions may have affected the cardiovascular systems, which may indicate a poor prognosis in patients with MSA. An analysis of HRV and the circadian rhythm of BP and HRV are useful in evaluating cardiac autonomic dysfunctions in MSA.

Autonomic assessment of cardiovascular disease.

Autonomic dysfunction plays a major role in the pathophysiology of many medical conditions, particularly cardiovascular disorders and diabetes mellitus. This article describes some of the methods used to assess cardiovascular autonomic function, and concentrates on the techniques that have a current or potential clinical application.