Abnormal Autonomic Function Tests Research Articles

A Study of Cardiac Autonomic Neuropathy in Patient with Diabetes Mellitus.

Atherosclerotic coronary artery disease, diabetic cardiomyopathy, and cardiac autonomic neuropathy (CAN) are the three categories into which the cardiovascular consequences of diabetes can be grouped. After all other potential causes have been ruled out, cardiovascular autonomic neuropathy-often referred to as CAN in the literature-is defined as the impairment of autonomic regulation of the cardiovascular system. Finding people with CAN is crucial because, if detected early enough, comprehensive therapies focusing on lifestyle, glucose management, and cardiovascular risk factors can reverse the course of CAN and delay its progression. In order to better understand CAN in individuals with diabetes mellitus (DM) and how it relates to risk factors, the current study was conducted. Sixty consecutive diabetic patients were selected to be included in our study, diagnosed as per the American Diabetes Association (ADA) and the European Association for the Study of Diabetes. The presence of CAN was assessed with the help of Ewing's Battery, composed of five bedside tests. Out of 60 patients, a total of 53 patients (88.3%) with DM had CAN. Of these, 38.3% showed early CAN, 38.3% showed definite CAN, and 7% showed severe CAN. The abnormal E:I (exhalation/inhalation) ratio, noticed in 75% of patients, was the most frequently observed abnormal autonomic function test that tests the parasympathetic nervous system. The ECG's QTc interval prolongation provides good specificity for diagnosing CAN as well as assessing its severity, but the majority of cases showed low sensitivity. Since CAN has a significant association with mortality, every patient diagnosed with DM should be evaluated for CAN at the time of diagnosis as well as on an annual basis thereafter, as recommended by the ADA. Optimal glycemic management and lifestyle modification at the initial stages of diabetes may prevent CAN-related complications.

Autonomic Nerve Involvement in Post-Acute Sequelae of SARS-CoV-2 Syndrome (PASC).

The novel SARS-CoV-2 virus and resulting COVID-19 global pandemic emerged in 2019 and continues into 2022. While mortality from COVID-19 is slowly declining, a subset of patients have developed chronic, debilitating symptoms following complete recovery from acute infection with COVID-19. Termed as post-acute sequelae of SARS-CoV-2 syndrome (PASC), the underlying pathophysiology of PASC is still not well understood. Given the similarity between the clinical phenotypes of PASC and postural orthostatic tachycardia syndrome (POTS), it has been postulated that dysautonomia may play a role in the pathophysiology of PASC. However, there have been only a few studies that have examined autonomic function in PASC. In this retrospective study, we performed an analysis of autonomic nerve function testing in PASC patients and compared the results with those of POTS patients and healthy controls. Our results suggest that a significant number of PASC patients have abnormal autonomic function tests, and their clinical features are indistinguishable from POTS.

Cardiovascular responses to tilting in Type 2 Diabetic patients

Background: Diabetes mellitus (DM) is a disorder with a debilitating effects on cardiac autonomic control. Multiple major cardiovascular risk factors associated with DM led diabetic patients at high risk of Cardiovascular Disease.
 Objective: To assess cardiovascular responses to tilting in Type 2 Diabetic patients (T2DM) with normal and abnormal autonomic function test.
 Methods: This experimental study was conducted on 60 patients of T2DM. Among them, 30 patients were with normal cardiovascular reflex test (group DN) and 30 patients were with abnormal test (group DA). Thirty(30) apparently healthy subjects with similar age and sex without any physical illness were enrolled as control. Tilt table test of all subjects was done by tilting at 60° for 10 min by using a motorized tilt table. Cardiovascular response to tilt test was assessed by calculating D Heart rate (Acceleration index and Brake index); DSBP (SBP 30s-0 and SBP1 min -0), DDBP (DBP 30s-0 and DBP1 min -0) after tilting. For statistical analysis, one-way ANOVA followed by Bonferroni post hoc was used.
 Results: In this study, the Acceleration index was significantly higher in patient group DN compared to control and DA(p<0.001). But the Brake index was significantly (p<0.01, p<0.05) lower in both group of patients compared to control. In addition, SBP 30sec-0 and SBP1 min-0 were significantly higher in DA than those of control and DN.DBP 30sec-0 and DBP1min-0 were significantly (p<0.001) lower in DA patients compared to DN and control.
 Conclusion: This study concluded that cardiovascular response to tilting was weak in T2DM patients and it was greatly affected in T2DM patients with abnormal autonomic function test.
 J Bangladesh Soc Physiol. 2020, December; 15(2): 78-84

Gulf war illness, post-HPV vaccination syndrome, and Macrophagic Myofasciitis. Similar disabling conditions possibly linked to vaccine-induced autoimmune dysautonomia.

1) To systematically review all original articles investigating the association of vaccines with gulf war illness, 2) To discuss gulf war illness, Macrophagic Myofasciitis, and post-HPV vaccination syndrome clinical similarities, 3) To discuss emergent pathogenetic mechanisms proposed for post-HPV vaccination syndrome that may be also relevant to gulf war illness and Macrophagic Myofasciitis. All original epidemiological studies (n = 11) found a positive association between vaccination and gulf war illness development. Chronic fatigue, widespread pain and cognitive impairment characterize the three syndromes under discussion. Anti-adrenergic receptor antibodies, dysautonomia and small fiber neuropathy have been recently described in patients with post-HPV vaccination syndrome. post-HPV vaccination syndrome, Macrophagic Myofasciitis, and gulf war illness analogy suggests that some vaccines or multiple vaccinations in a very short period of time may induce, in susceptible individuals, chronic pain, fatigue and dyscognition. Vaccine-induced autoimmune dysautonomia is hypothesized as the common pathogenetic mechanism for this symptom cluster. Further research on the presence of small fiber neuropathy, adrenergic receptor antibodies, and abnormal autonomic function tests in the three syndromes under discussion may help to elucidate this hypothesis.

Left ventricular remodelling and cardiac chamber sizes in long-term, normoalbuminuric type 1 diabetes patients with and without cardiovascular autonomic neuropathy

AimsType 1 diabetes is associated with increased cardiovascular (CV) morbidity and mortality, and cardiovascular autonomic neuropathy (CAN) is an important CV risk factor. The study aimed to explore associations between CAN and altered cardiac chamber sizes in persons with type 1 diabetes. MethodsThis was a cross-sectional study of 71 asymptomatic, normoalbuminuric participants with long-term type 1 diabetes (39 with CAN, determined by >1 abnormal autonomic function test) examined with cardiac multi detector computed tomography scans, which allowed measurements of left ventricular mass and all four cardiac chamber volumes. Cardiac chambers were indexed according to body surface area (ml/m2 or g/m2). ResultsPersons with and without CAN had mean ± SD age of 57 ± 7 and 50 ± 8 years (p < 0.001) and diabetes duration of 36 ± 11 and 32 ± 9 years (p < 0.05), respectively. Increasing autonomic dysfunction, evaluated by decrease in heart rate variability during deep breathing (in beats per minute), was associated with larger right (−0.5, 95% CI −1.0 to −0.0, p < 0.05) and trend towards larger left (−0.4, 95% CI −0.8–0.0, p < 0.1) ventricular volumes in multivariable linear regression. ConclusionsOur results suggest that impaired autonomic function may be associated with modest enlargement of ventricular volumes; this might be an early sign of progression towards heart failure.

Recent advances in orthostatic hypotension presenting orthostatic dizziness or vertigo.

Orthostatic hypotension (OH), a proxy for sympathetic adrenergic failure, is the most incapacitating sign of autonomic failure. Orthostatic dizziness (OD) is known to be the most common symptom of OH. However, recent studies have demonstrated that 30-39% of patients with OH experienced rotatory vertigo during upright posture (i.e., orthostatic vertigo, OV), which challenges the dogma that OH induces dizziness and not vertigo. A recent population-based study on spontaneously occurring OD across a wide age range showed that the one-year and lifetime prevalence of OD was 10.9 and 12.5%, respectively. Approximately 83% of patients with OD had at least one abnormal autonomic function test result. So far, 11 subtypes of OD have been proposed according to the pattern of autonomic dysfunction, and generalized autonomic failure of sympathetic adrenergic and parasympathetic cardiovagal functions was the most common type. Four different patterns of OH, such as classic, delayed, early, and transient type have been found in patients with OD. The head-up tilt test and Valsalva maneuver should be performed for a comprehensive evaluation of sympathetic adrenergic failure in patients with OD/OV. This review summarizes current advances in OH presenting OD/OV, with a particular focus on the autonomic dysfunction associated with OD.

Alteration of autonomic function is associated with disease severity in patients with bronchial asthma

Background and Aim: Abnormality in the autonomic regulation of the airway results in airway obstruction in bronchial asthma. However, autonomic abnormality in asthmatic patients is generalized and is not confined to airway only. Therefore, the present study was conducted to assess the abnormality of autonomic nervous system (ANS) and its association with disease severity in bronchial asthma patients. Methods: Sixty patients of bronchial asthma aged between 15 and 50 years were included in the study. After taking informed consent, the duration of asthma was noted in each of these patients and six noninvasive ANS testing namely deep breathing test, orthostatic test, 30:15 ratio, sustained hand grip test, valsalva manoeuvre and cold pressure test was performed. Results: The study population consisted of 60 bronchial asthma patients (34 males and 26 females) and 60 controls (32 males and 28 females). It was found that out of 60 patients, 46 patients had abnormal autonomic function test values ( P P Conclusion: Bronchial asthma patients displayed definitive dysfunction of ANS as compared with age and sex-matched controls. With severity and chronicity of asthma, the autonomic function was proportionately attenuated. Parasympathetic overactivity appears to be closely linked to the severity of bronchial asthma.

A study of Autonomic Dysfunction in bronchial asthma patients in a tertiary care centre of central India

Introduction: bronchial asthma is a chronic inflammatory disorders of airways characterised by exaggerated bronchoconstriction due to certain indirect (e g dust, pollen, allergens, cold air) or direct (inhaled methacholine) stimuli. Autonomic system plays an important role in regulation of airways and their secretion. This study was planned to demonstrate existence of autonomic dysfunction in pathophysiology of bronchial asthma. Material & Methods: Present study is undertaken in 45 subjects who were divided in to 2 groups cases and controls depending up on age and sex and similar characteristics. 7 different non-invasive tests are applied in to all subjects to evaluate their autonomic function status. Results: It was found that out of 45 patients 33 patients had abnormal autonomic function tests. Comparing the duration of bronchial asthma, 12 patients had duration 5 years out of these 30 had abnormal tests and only 3 patients had normal test. Comparing the severity of bronchial asthma and autonomic dysfunction, Out of 45 patients 24 were classified as having severe bronchial asthma. 21 of the study patients had only parasympathetic dysfunction i.e. 46.66%. 12 had both sympathetic and parasympathetic dysfunction i.e.40% and only 6 had isolated sympathetic dysfunction i.e. 13.33%. Conclusions: There is higher incidence of autonomic dysfunction in bronchial asthma patients. Parasympathetic hyper responsiveness appears to be the main pathological factor in the genesis of bronchial asthma

Left Ventricular Systolic and Diastolic Function in Normotensive Type 2 Diabetic Patients With or Without Autonomic Neuropathy

We investigated the relation between diabetic autonomic neuropathy (DAN) and left ventricular (LV) function in 59 patients with type 2 diabetes mellitus (T2DM) free of coronary artery disease (CAD) or hypertension. Diabetic autonomic neuropathy was established by ≥2 abnormal autonomic nervous function tests. Left ventricular systolic and diastolic functions were assessed by resting radionuclide ventriculography. Compared with non-DAN patients (n=24), patients with DAN (n=35) had an increased adjusted atrial contribution to ventricular filling (A/V%, 30.1%±8.2% vs 26.5%±5.1%; P=.031), suggestive of diastolic dysfunction (DD). There were no differences between the 2 groups in peak filling rate, first 1/3 filling fraction, ejection fraction, cardiac output, and cardiac index. Patients with diabetic autonomic neuropathy had an increased heart rate (77.8±6.3 vs 69.3±3.3 bpm; P<.0001) and a higher rest LV workload (10,072±1165 vs 8606±1075 bpm mm Hg; P<.0001). Patients with DAN T2DM without CAD or hypertension have DD, increased A/V index, and a higher LV working load than non-DAN patients.

Electrocardiographic findings in sickle cell cardiovascular autonomic neuropathy

There is a lack of data on the relationship between cardiovascular autonomic neuropathy (CAN) and electrocardiographic parameters in sickle cell anaemia. The purpose of the study was to compare the electrocardiographic findings in adult sickle cell anaemia patients with CAN with those of patients without this complication. A cross sectional study was done using 62 consecutively recruited sickle cell anaemia patients who met the inclusion criteria for the study. Cardiovascular autonomic dysfunction was determined based on abnormal values in at least two of five non-invasive tests: Valsalva manoeuver, heart rate variation during deep breathing, heart rate response to standing, blood pressure response to sustained hand grip, and blood pressure response to standing. The subjects were subsequently evaluated with electrocardiography. Sickle cell anaemia patients with CAN had statistically significantly increased P-wave duration (p < 0.001), PR-interval (p < 0.05) and QTc dispersion (p < 0.05) compared with patients without CAN. Significantly increased frequencies of Q waves and first degree atrio-ventricular block were found in patients with CAN than in those without CAN (p = 0.026, p = 0.014, respectively). Significant correlations were noted between the severity of CAN [number of abnormal autonomic function tests (AFT)] and (1) P-wave duration (p = 0.008), (2) PR- interval (p = 0.013). Significant association was found between the number of abnormal AFT and (1) presence of Q-waves, and (2) degree of anaemia (haematocrit class). Electrocardiographic features consistent with atrio-ventricular and ventricular repolarization abnormalities are associated with CAN in sickle cell anaemia. Further studies are required to evaluate the prognostic implications of these findings in sickle cell patients with cardiovascular autonomic dysfunction.

MIBG scintigraphy for differentiating Parkinson's disease with autonomic dysfunction from Parkinsonism‐predominant multiple system atrophy

Parkinson's disease (PD) with autonomic dysfunction is difficult to differentiate from Parkinsonism-predominant multiple system atrophy (MSA-p). This study aimed to analyze the validity of MIBG scintigraphy for PD with autonomic dysfunction and MSA-p. Thirty-nine patients (PD: 27 patients, MSA-p type: 12) and 12 age-matched controls were prospectively enrolled and underwent MIBG scintigraphy and autonomic function test (AFT). We separately calculated early and delayed heart-to-mediastinal (H/M) ratio and washout rates (WRs). AFT was composed of sympathetic skin reflex and parasympathetic tests based on heart rate variability. Abnormal AFT was observed in 17 (63%) of PD and 10 (83%) of MSA-p. On comparing PD with abnormal AFT with MSA-p, either the early or delayed H/M ratio in PD was not different from that in MSA-p (P > 0.05). Only the WR could differentiate PD with abnormal AFT from MSA-p (47.07 +/- 57.48 vs. 31.39 +/- 31.52, respectively) (P = 0.026). According to the results, WR may be more useful than the early and delayed H/M ratio to distinguish MSA-p from PD with abnormal AFT. Furthermore, the MIBG uptake did not reflect the disease duration or severity.

Autoantibodies to Autonomic Nerves Associated With Cardiac and Peripheral Autonomic Neuropathy

This study examines whether autonomic nerve autoantibodies (ANabs) are associated with development of autonomic neuropathy using a prospective study design. A group of type 1 diabetic patients were followed prospectively with regard to autonomic nerve function on four occasions. At the third examination, 41 patients were tested for ANabs (complement-fixing autoantibodies to the sympathetic ganglion, vagus nerve, and adrenal medulla), and the results were related to cardiac autonomic nerve function (heart rate variation during deep breathing [expiration/inspiration ratio] and heart-rate reaction to tilt [acceleration and brake index]) and to peripheral sympathetic nerve function (vasoconstriction after indirect cooling [vasoconstriction index]). ANabs were detected in 23 of 41 (56%) patients at the third examination. Compared with patients without ANabs (ANabs-), patients with ANabs (ANabs+) showed significantly higher frequencies of at least one abnormal cardiac autonomic nerve function test at the third examination (17 of 23 [74%] vs. 7 of 18 [39%]; P = 0.03) and fourth examination (15 of 21 [71%] vs. 4 of 16 [25%]; P < 0.01). In contrast, there was no similar difference at the first or second examination. The relative risk for ANabs(+) patients to develop cardiac autonomic neuropathy at follow-up was 7.5 (95% CI 1.72-32.80). The vasoconstriction index was more abnormal in ANabs+ than in ANabs- patients at the fourth examination (median 1.40 [interquartile range 1.58] vs. 0.35 [2.05]; P = 0.01). ANabs were associated with future development of cardiac and peripheral autonomic neuropathy in diabetic patients, implying an etiological relationship between nervous tissue autoimmunity and these diabetes complications.

Erythropoietin deficiency and anaemia in multiple system atrophy.

Serum erythropoietin (EPO) levels are partially controlled by the sympathetic outflow to the kidney. We have studied whether patients with multiple system atrophy (MSA), known to be associated with dysautonomia, are EPO-deficient. Eighteen MSA patients were studied along with 32 idiopathic Parkinson's disease (PD) patients, 23 controls with iron-deficiency anaemia, and 18 healthy individuals. Serum creatinine was normal in all groups. Mean haemoglobin (Hb) concentration in MSA patients was 13.7 +/- 1.7 g/dL. Four MSA patients had unexplained anaemia (minimum Hb: 10.5 g/dL) and abnormal autonomic function tests including significant postural hypotension, whereas none of the PD patients was anaemic. Serum EPO levels were suppressed in relation to anaemia in MSA patients compared to elevated EPO levels in iron-deficiency anaemia patients (difference of regression lines P < 0.001), indicating EPO deficiency in the anaemic MSA patients. Serum EPO levels in PD patients were within normal range. A subset of MSA patients has anaemia and postural hypotension, which may be associated with EPO deficiency. This may have therapeutic implications.

Cardiac autonomic dysfunction in AIDS is not secondary to heart failure

Objective: Heart rate variability (HRV) is a marker of cardiovascular autonomic tone, and is also known to be reduced in association with cardiac dysfunction. Abnormal autonomic function tests are common in HIV infected individuals, but the contribution of heart disease to such findings is not known. Spectral analysis of heart rate variability is a sensitive technique for measurement of cardiovascular autonomic function, which also allows differential assessment of parasympathetic and sympathetic components. The aim of this study was to characterise the nature of autonomic dysfunction in patients with AIDS and to compare our findings with those seen in HIV seronegative patients with established heart disease. Methods: HRV was measured prospectively by spectral analysis in 10 subjects with dilated cardiomyopathy (age 45.7±6.9 years), 10 subjects with AIDS and no clinical evidence of heart disease (age 37.9±5.4 years), and 10 healthy HIV seronegative controls (age 41.7±13.9 years). Results: All components of HRV were reduced in subjects with cardiomyopathy ( P<0.005), and markedly so in subjects with AIDS ( P<0.0001) compared with controls. Conclusions: HIV infection may be associated with severe global autonomic dysfunction, which is not related to heart disease.

Cardiovascular Autonomic Dysfunction and Hemodynamic Response to Anesthetic Induction in Patients with Coronary Artery Disease and Diabetes Mellitus

Autonomic neuropathy is a major complication of diabetes mellitus and is reported to be associated with increased perioperative hemodynamic instability.We investigated the relationship between autonomic dysfunction and hemodynamic response to anesthetic induction in diabetic and nondiabetic patients with coronary artery disease. We studied 60 patients scheduled for coronary artery surgery, 30 suffering from diabetes mellitus. Preoperative evaluation included traditional cardiovascular autonomic function tests (coefficient of variation of 150 beat-to-beat intervals in heart rate at rest, heart rate response to deep breathing, and heart rate and arterial blood pressure response to standing), spectral analysis of blood pressure and heart rate variability (HRV), and the computation of spontaneous baroreflex sensitivity. After premedication with clorazepate, anesthesia was induced with sufentanil (0.5 [micro sign]g/kg), etomidate (0.1-0.2 mg/kg), and vecuronium (0.1 mg/kg). Heart rate and blood pressure before anesthetic induction and before and after tracheal intubation were compared between groups. Autonomic function tests, spectral analysis of HRV, and spontaneous baroreflex sensitivity revealed significant differences between patient groups. Most diabetic patients (n = 23) had one or more abnormal test results, in contrast to most nondiabetic patients, who did not show signs of autonomic neuropathy (n = 23). There was no relationship between cardiovascular autonomic function and hemodynamic behavior during anesthetic induction. The blood pressure response to anesthetic induction was not different between patient groups, even when comparing the subgroups with and without abnormal autonomic function tests. These findings indicate that increased hemodynamic instability during anesthetic induction is not obligatory in patients with diabetes mellitus and autonomic dysfunction. Implications: This study indicates that increased hemodynamic instability during anesthetic induction is not obligatory in patients with coronary artery disease and autonomic dysfunction. (Anesth Analg 1999;88:985-91)

Cardiovascular autonomic dysfunction and hemodynamic response to anesthetic induction in patients with coronary artery disease and diabetes mellitus.

Autonomic neuropathy is a major complication of diabetes mellitus and is reported to be associated with increased perioperative hemodynamic instability. We investigated the relationship between autonomic dysfunction and hemodynamic response to anesthetic induction in diabetic and nondiabetic patients with coronary artery disease. We studied 60 patients scheduled for coronary artery surgery, 30 suffering from diabetes mellitus. Preoperative evaluation included traditional cardiovascular autonomic function tests (coefficient of variation of 150 beat-to-beat intervals in heart rate at rest, heart rate response to deep breathing, and heart rate and arterial blood pressure response to standing), spectral analysis of blood pressure and heart rate variability (HRV), and the computation of spontaneous baroreflex sensitivity. After premedication with clorazepate, anesthesia was induced with sufentanil (0.5 microg/kg), etomidate (0.1-0.2 mg/kg), and vecuronium (0.1 mg/kg). Heart rate and blood pressure before anesthetic induction and before and after tracheal intubation were compared between groups. Autonomic function tests, spectral analysis of HRV, and spontaneous baroreflex sensitivity revealed significant differences between patient groups. Most diabetic patients (n = 23) had one or more abnormal test results, in contrast to most nondiabetic patients, who did not show signs of autonomic neuropathy (n = 23). There was no relationship between cardiovascular autonomic function and hemodynamic behavior during anesthetic induction. The blood pressure response to anesthetic induction was not different between patient groups, even when comparing the subgroups with and without abnormal autonomic function tests. These findings indicate that increased hemodynamic instability during anesthetic induction is not obligatory in patients with diabetes mellitus and autonomic dysfunction. This study indicates that increased hemodynamic instability during anesthetic induction is not obligatory in patients with coronary artery disease and autonomic dysfunction.

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

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

The hypertension of autonomic failure and its treatment.

We studied the incidence and severity of supine hypertension in 117 patients with severe primary autonomic failure presenting to a referral center over a 9-year period. Patients were uniformly characterized by disabling orthostatic hypotension, lack of compensatory heart rate increase, abnormal autonomic function tests, and unresponsive plasma norepinephrine. Fifty-four patients had isolated autonomic impairment (pure autonomic failure). Sixty-three patients had central nervous system involvement in addition to autonomic impairment (multiple-system atrophy). Patients were studied off medications, in a metabolic ward, and on a controlled diet containing 150 mEq of sodium. Fifty-six percent of patients had supine diastolic blood pressure > or =90 mm Hg. The prevalence of hypertension was slightly greater in females (63%) than in males (52%). Potential mechanisms responsible for this hypertension were investigated. No correlation was found between blood volume and blood pressure. Similarly, plasma norepinephrine (92+/-15 pg/mL) and plasma renin activity (0.3+/-0.05 ng/mL per hour) were very low in the subset of patients with pure autonomic failure and supine hypertension (mean systolic/diastolic pressure, 177 +/- 6/108 +/- 2 mm Hg, range 167/97 to 219/121). Supine hypertension represents a challenge in the treatment of orthostatic hypotension. We found these patients to be particularly responsive to the hypotensive effects of transdermal nitroglycerin. Doses ranging from 0.025 to 0.1 mg/h decreased systolic blood pressure by 36+/-7 mm Hg and may effectively treat supine hypertension overnight, but the dose should be individualized and used with caution.

Relationship between autonomic function and plasma fibrinogen, viscosity, and elements of fibrinolytic activity in diabetic nephropathy

Twenty-three insulin-dependent diabetics with proteinuria (3.3 g/day: range 0.3 to 8.9) and azotemia (creatinine clearance: 58 mL/min, range 30 to 112) were tested for 24-h mean arterial blood pressure; instantaneous heart rate variations to a computerized protocol involving timed ventilation, assumption of upright posture, and Valsalva maneuver; plasma fibrinogen, viscosity, fibrinolytic activity, and plasminogen activator inhibitor. These were to test the hypothesis that autonomic dysfunction is associated with altered concentrations of plasma fibrinogen, fibrinolytic activity, viscosity, and plasminogen activator inhibitor. We have previously shown the absence of a correlation between level of blood pressure, clinical and standard laboratory testing, and the results of the autonomic function testing protocol used in this study. In this group of patients, plasma fibrinogen concentration was correlated (positively) with mean arterial pressure and (negatively) with heart rate variation in response to the Valsalva maneuver. The greater the mean arterial pressure or the worse the Valsalva results, the higher the plasma fibrinogen concentration. In addition, patients with one or no abnormal autonomic function tests had a mean fibrinogen of less than 400 mg/dL compared to the group of patients with two or more abnormal tests who had a mean fibrinogen of 500 mg/dL. In patients with demonstrated parasympathetic abnormalities, postural heart rate variation testing also discerned a differential in plasma fibrinogen. Lower concentration of plasminogen activator inhibitor throughout the day, and greater fibrinolytic activity in the morning were also noted to be present in patients with abnormal heart rate response to the Valsalva maneuver. We conclude that there are relationships between high blood pressure, autonomic function, and hemostatic factors favoring thrombogenesis that may be related by common mechanisms and treatments in the diabetic with kidney disease.

Atrial natriuretic factor and digoxin-like immunoreactive factor in diabetic patients: their interrelation and the influence of the autonomic nervous system.

In diabetic patients, several factors contribute to volume expansion and have to be counteracted by humoral and neuronal feedback control systems. We investigated N-terminal proatrial natriuretic factor (ANF1-98) and digoxin-like immunoreactive factor (DLIF), which are two counteracting hormones, and their interrelationship, with additional consideration given to autonomic nervous function in diabetic patients. ANF1-98 and DLIF were measured in 64 diabetic patients. Autonomic nervous function was assessed using nine autonomic nervous function tests. The patients were subdivided into two groups, one with four or more (group 1) and one with less than four abnormal results in autonomic function tests (group 2). Compared with group 2, group 1 demonstrated detectable DLIF levels less often (17.2 vs. 45.7, P = 0.0195) and increased levels of ANF1-98 (mean +/- SEM: 850.0 +/- 108.8 vs. 554.8 +/- 45.9 pmol/L, P = 0.0099). However, the groups did not differ in blood pressure, daily sodium, and daily potassium excretion. The number of abnormal autonomic function tests correlated significantly with ANF1-98 (P = 0.0002). In patients with detectable DLIF, DLIF correlated with ANF1-98 (P = 0.0080). These results demonstrate close interactions between the autonomic nervous system and the two natriuretic hormones. In patients with autonomic nervous dysfunction, higher levels of ANF may possibly compensate for the lack of the natriuretic DLIF to counteract hypertension and chronic volume expansion.