Cardiac Autonomic Nervous Dysfunction Research Articles

Complications during Adolescence Predict Mortality in Young Adults with Childhood Onset Type 1 Diabetes

Objective. Microvascular complications increase the risk of cardiovascular disease and premature death in adults with type 1 diabetes. We examined the association between microvascular complications during adolescence, including cardiac autonomic nerve dysfunction and subsequent mortality. Research Design and Methods. We undertook data linkage with the Australian National Death Index in a cohort of 409 adolescents (diagnosed between 1973 and 1993), 48% male, median age at final complications assessment 17.4 years (interquartile range: 16.0–18.9), followed longitudinally for median 22.3 years (21.0–23.4) from diagnosis. Generalized estimating equations (GEE) were used to examine associations between mortality and adolescent complications. Mortality risk was calculated as standardized mortality ratio (SMR). Results. At final adolescent visit, 20% had CAN abnormality, 30% abnormal pupillary response, 20% albuminuria, 40% early elevation of albumin excretion rate (AER) and 45% retinopathy. Data linkage 8–13 years later showed 14 were deceased (3% of cohort), 57% male, median age 28.3 years (24.8–32.9). Acute or chronic diabetes complications accounted for 25% of deaths. In multivariable GEE, elevated AER (OR 4.54, 1.23–16.80, p=0.030), pupillary abnormality (OR 4.27, 1.20–15.22, p=0.023), systolic blood pressure SDS (OR 2.17, 1.26–3.74, p=0.005) and CAN (OR 4.65, 1.03–21.0, p=0.045) predicted mortality. HbA1c was not significant. SMR was 2.5 (1.4–4.2) and was higher in females (SMR 3.5, 1.3–7.8) but not in males (SMR 2.1, 0.9–4.0). Conclusion. Mortality in young adults with type 1 diabetes is predicted by subclinical markers of autonomic neuropathy and elevated AER during adolescence, but not glycemia. Mortality was over twice that of the background population in females but not in males.

Effect of physical exercise on non-linear parameters of heart rate variability in Chronic Obstructive Pulmonary Disease

Background: Chronic Obstructive Pulmonary Disease (COPD) is associated with autonomic nerve dysfunction. Nonlinear methods of heart rate variability (HRV) analysis have been gaining interest as a method of detecting changes in cardiac autonomic nerve function. Regular practice of physical exercise may cause improvement of this impaired autonomic nerve function. Objectives: To assess the effect of physical exercise on nonlinear measures of HRV analysis in male patients with COPD. Methods: This prospective interventional study was carried out in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka in 2018 on 60 diagnosed male COPD patients aged 40-75 years with disease duration of at least 5 years selected from the Department of Respiratory Medicine, BSMMU, Dhaka. Thirty patients underwent physical exercise (walking for 30 minute and pursed lip and diaphragmatic breathing 10 minuts)for 3 months in addition to standard treatment. Thirty (30) patients received only standard treatment for 3 months. For comparison, 30 age matched apparently healthy males were also enrolled. HRV data of all patients were recorded before and after 3 months of follow up. HRV data of healthy controls were recorded once at baseline. For assessing autonomic dysfunction, nonlinear parameters of HRV were recorded by Power Lab 8/35. For statistical analysis, paired sample t-test and independent sample t-test were done as applicable. Results: SD1, SD2 and SD1/ SD2 were found significantly lower in COPD patients compared to healthy controls at baseline. After 3 months of physical exercise, significant increment of these parameters occurred with a trend of improvement in cardiac autonomic nerve function in these patients. Conclusion: This study concluded that physical exercise can improve cardiac autonomic nerve dysfunction function in COPD patients. J Bangladesh Soc Physiol. 2022, June; 17(1): 6-13

Cardiac Autonomic Nerve Dysfunction Predicts Incident Retinopathy and Early Kidney Dysfunction in Adolescents With Type 1 Diabetes.

Cardiac autonomic neuropathy (CAN) may contribute to vascular complications in diabetes. We hypothesized that adolescents with CAN are at greater risk of diabetic retinopathy and early kidney dysfunction. In this prospective longitudinal study of 725 adolescents with type 1 diabetes without retinopathy and albuminuria at baseline, early CAN was defined as one or more abnormalities in seven heart rate tests derived from a 10-min electrocardiogram. Retinopathy was defined as the presence of one or more microaneurysms, early kidney dysfunction as an albumin excretion rate (AER) >7.5 μg/min, and albuminuria as an AER >20 μg/min. Multivariable generalized estimating equations were used to examine the association between CAN and retinopathy or early kidney dysfunction. Cox proportional hazards regression analysis was used to assess cumulative risks of incident retinopathy and albuminuria. At baseline, the mean age of the sample was 13.6 ± 2.6 years, 52% were male, and mean diabetes duration was 6.1 ± 3.3 years. Over a median follow-up of 3.8 (interquartile range 2.2-7.5) years, the complication rate 27% for retinopathy, 16% for early kidney dysfunction, and 3% for albuminuria. The mean study HbA1c was 72.3 ± 16 mmol/mmol (8.6 ± 1.4%). CAN predicted incident retinopathy (odds ratio 2.0 [95% CI 1.4, 2.9]) and early kidney dysfunction (1.4 [1.0, 2.0]) after adjusting for HbA1c and diabetes duration. CAN also predicted retinopathy (hazard ratio 1.57 [95% CI 1.09, 2.26]) and albuminuria (2.30 [1.05, 5.04]) independently of HbA1c. CAN predicted incident retinopathy and kidney dysfunction in adolescents with type 1 diabetes, likely reflecting autonomic microvascular dysregulation contributing to complications. Therefore, screening and interventions to reduce CAN may influence the risk of complications.

Comparison of Tp-e interval, QTc interval and Tp-e/QTc ratios between non-diabetic and prediabetic population

Aim: Increased blood glucose concentration and cardiac autonomic nerve dysfunction are associated with an increased risk of malignant ventricular arrhythmia. Tp-e interval, Tp-e/QT, and Tp-e/QTc are novel parameters used to assess ventricular arrhythmogenicity. This study aimed to compare these parameters with the healthy control group in prediabetics. Materials and Methods: The ECGs of 58 prediabetic patients (29 male, 59.74 ±13.25 years) were examined and matched with the ECGs of 59 healthy controls (28 male, 61.75 ± 12.66 years) that were matched with gender, age and body mass index. From the 12-lead ECG Tp-e and QT intervals were measured and by Bazett's formula QTc was calculated. Tp-e/QT and Tp-e/QTc proportions were also determined. Results: In prediabetic patients, the mean Tp-e interval was significantly longer than the control group (79.07 ± 8.17 vs 72.03 ± 9.77 ms, respectively; p 0.001). Also in prediabetic, Tp-e/QT and Tp-e/QTc were significantly higher than the controls (respectively 0.21 ± 0.25 vs 0.19 ± 0.03 and 0.19 ± 0.02 vs 0.17 ± 0.02; p 0.001). Other ECG parameters were similar in both groups. HbA1c levels and glucose levels were positively correlated with Tp-e / QT and Tp-e / QTc.Conclusion: Prediabetes increases the risk of ventricular arrhythmogenesis by increasing the transmural dispersion of repolarization. The addition of Tp-e interval and TP-e / QT measurements to the routine ECG evaluation of prediabetic patients can be used to predict arrhythmia risk.

Impact of Slow breathing exercise on heart rate variability in male Type 2 diabetes mellitus

Background: Reduced heart rate variability (HRV) with cardiac autonomic nerve dysfunction has been found in Type 2 Diabetes Mellitus (T2DM) patients. Yoga based slow breathing exercise (SBE) improved this autonomic functions in healthy subjects.
 Objectives: To assess the effect of SBE on cardiac autonomic nerve function(CANF) by power spectral analysis of HRV in patients with T2DM.
 Methods: This prospective interventional study was carried on 30 male diagnosed T2DM patients aged 45-55 years with disease duration 5-10 years enrolled from Out Patient Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, Dhaka. They performed SBE for 30 minutes twice daily for 3 months. Thirty apparently healthy age, BMI matched male who did not undergo any type of exercise were included as control. To assess the cardiac autonomic nerve function, power spectral analysis of HRV of all patients were done before and after 3 months of SBE. HRV data were recorded by polyrite D (RMS India). For statistical analysis, independent sample and paired sample t-test were used.
 Results: The preintervention values of Low frequency (LF) normalized unit(nu) and Low frequency/High frequency( LF/HF) ratio were significantly (p<0.001) higher and the values of LF power, HF power, HF normalized unit (HF nu) were significantly (p<0.001) lower in all diabetic patients compared to control. The postintervention values of LF power, HF power, HF nu increased significantly (p<0.001) and the LF nu, LF/HF ratio decreased significantly (p<0.001)compared to their pre-intervention values in T2DM. There were no significant differences between the post intervention values of LF nu, HF nu and LF/HF ratio in T2DM and the control.
 Conclusion: Impaired cardiac autonomic nerve function was significantly improved by SBE in T2DM.
 J Bangladesh Soc Physiol. 2019, December; 14(2): 63-68

Correlations of thyroid hormone with deceleration capacity of heart rate and heart rate variability in children with hyperthyroidism

To investigate deceleration capacity of heart rate (DC), acceleration capacity of heart rate (AC), and heart rate variability (HRV) in children with hyperthyroidism and the correlations of serum thyroid hormone levels with DC, AC, and HRV. A total of 47 children with hyperthyroidism were enrolled as hyperthyroidism group and 50 healthy children were enrolled as control group. The subjects in the two groups underwent 24-hour ambulatory electrocardiography. The two groups were compared in terms of DC, AC, heart rate (HR), HRV parameters [standard deviation of normal-to-normal RR intervals (SDNN), standard deviation of average normal-to-normal RR intervals (SDANN), root mean square of successive differences between adjacent RR intervals (RMSSD), low-frequency power (LF), and high-frequency power (HF)]. The correlations of thyroid hormone indices [free triiodothyronine (FT3) and free thyroxin (FT4)] with DC, AC, and HRV were analyzed. Compared with the control group, the hyperthyroidism group had significantly lower DC, SDNN, SDANN, RMSSD, LF, and HF and significantly higher AC and HR (P<0.05). In the children with hyperthyroidism, serum FT3 and FT4 levels showed significant negative correlation with DC, SDNN, SDANN, RMSSD, LF, and HF and significant positive correlation with AC and HR (P<0.05). Children with hyperthyroidism have cardiac autonomic nerve dysfunction manifested as reduced vagal tone. Vagal tone decreases with the increasing serum thyroid hormone levels, suggesting an increased risk of cardiovascular disease.

Effect of Deep Relaxation Technique on Cardiac Autonomic Dysfunction in Type 2 Diabetes Mellitus

Background: Type 2 Diabetes Mellitus (T2DM) may be associated with autonomic dysfunction. Performance of deep relaxation technique (DRT) may cause upturn of this deranged nerve function.Objective: To evaluate the impact of DRT on cardiac autonomic nerve function by analysis of time domain series of Heart Rate Variability (HRV) in T2DM patients.Methods: This prospective study was carried out on 30 female T2DM patients aged 50-55 years with duration of diabetes of 5-10 years enrolled from the Out Patient Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, Dhaka. They performed DRT (20 minutes twice daily) for 3 months. Thirty apparently healthy female with similar age who did not perform DRT or any other form of exercise, were included as control. To assess the cardiac autonomic nerve function, time domain measures of HRV of all subjects were recorded by a data acquisition device Power Lab (Australia). HRV data of all subjects were collected at baseline (pre) and also after 3 months(Post). For statistical analysis, paired and independent sample t-test were used.Results: The pre-intervention values of resting HR was significantly higher (p&lt;0.001) and mean R-R interval, SDRR, CVRR, SDSD, RMSSD and pRR50% were significantly lower (p&lt;0.001) in all diabetic patients compared to control. After 3 months of DRT, there was significant decrement in resting mean heart rate (p&lt;0.01) and significant increment in mean R-R interval, SDRR, CVRR, SDSD, RMSSD and pRR50% (p&lt;0.001) compared to their pre-intervention values.Conclusion: Cardiac autonomic nerve dysfunction may occur in T2DM and 3 months regular practice of DRT mayy significantly improv cardiac autonomic nerve function with parasympathetic dominance.J Bangladesh Soc Physiol. 2018, June; 13(1): 22-28

Association between cardiac autonomic nervous dysfunction and the severity of coronary lesions in patients with stable coronary artery disease.

ObjectiveAutonomic dysfunction is recognized in patients with coronary artery disease (CAD) and is related to worse cardiovascular outcome. This study aimed to evaluate cardiac autonomic nervous function by heart rate recovery (HRR) and heart rate variability (HRV), and demonstrate their relationship with the severity of coronary lesions in patients with stable CAD (SCAD).MethodsConsecutive patients without CAD (controls, n = 65) and those with SCAD (n = 63) were included in this study. Patients with SCAD were further divided into single- or two-/three-vessel disease, as well as <70% or ≥70% stenosis subgroups. The association between HRR/HRV and coronary lesions was analysed.ResultsHRR and HRV values were significantly lower in the SCAD group compared with the control group. Multivariate logistic regression analysis showed that abnormal HRR and HRV were risk factors of SCAD. Moreover, delayed HRR was a risk factor of the severity of coronary lesions.ConclusionsOur results show that autonomic function is impaired in patients with SCAD and delayed HRR is closely related to the severity of coronary lesions.

The relationship of one-leg standing time with peripheral nerve function and clinical neuropathy in patients with type 2 diabetes.

This study aimed at exploring physical fitness including postural stability in relation to peripheral nerve function and clinical neuropathy in patients with type 2 diabetes across a wide range of ages. We analyzed data collected from 139 patients with type 2 diabetes aged between 19 and 81years, which included the peripheral nerve conduction parameters and coefficient of variation for normal R-R intervals (CVRR) at rest and during deep breathing. The results of neurological examinations to diagnose probable and confirmed diabetic neuropathies based on the minimal criteria proposed by the Toronto diabetic neuropathy expert group and a battery of physical fitness tests including one-leg standing time with eyes open were also assessed. Multiple linear and logistic regressions were used to estimate the relationships of the physical fitness measures with the parameters of peripheral and cardiac autonomic nerve functions and clinical neuropathies, respectively. Receiver operating characteristic curves were generated to depict the relation between sensitivity and specificity of one-leg standing time for probable and confirmed neuropathies. After adjustment for age and other potential confounders, one-leg standing time correlated with peripheral and cardiac autonomic nerve functions as well as with probable and confirmed neuropathies. The one-leg standing time of 23s was found to be 66 and 63% sensitive and 81 and 77% specific for diagnosing probable and confirmed neuropathies, respectively. Short one-leg standing time was associated with peripheral and cardiac autonomic nerve dysfunction and clinical neuropathy in patients with type 2 diabetes, independent of age.

Effect on Time Domain Parameters of HRV after Slow Breathing Exercise in Type 2 Diabetes Mellitus

Background: Cardiac autonomic nerve dysfunction has been associated with Type 2 Diabetes Mellitus (T2DM) with reduced Heart Rate Variability (HRV). Regular practice of slow breathing exercise (SBE) improves cardiac autonomic nerve function.Objective: To assess the effects of slow breathing exercise on cardiac autonomic nerve function by analysis of HRV in patients with Type 2 Diabetes Mellitus (T2DM).Methods: This prospective interventional study was carried out in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University in 2015. For this, total 30 male diagnosed T2DM patients from the Out Patient Department of Endocrinology, BSMMU aged 45-55 years with diseases duration of 5-10 years were included in the study group. All the patients underwent slow breathing exercise (SBE -30 mins twice daily) for 3 months along with medical treatment. Mean heart rate (HR), mean R-R interval, standard deviation of the NN intervals (SDNN), Square root of mean squared differences of successive N-N intervals (RMSSD) of HRV parameters were recorded at the beginning of 3 months and also at the end of 3 months of study period. Thirty age, BMI matched healthy subject also included as control. For statistical analysis paired and unpaired sample t-test were done as applicable.Results: In this study, Pre-exercise value of mean HR was significantly higher (p&lt; 0.001) and Pre-exercise values of mean R-R interval, SDNN and RMSSD were significantly lower (p&lt; 0.001) in diabetic patients in comparison to control. After 3 months of performing SBE, post exercise values of all parameters were improved significantly (p&lt; 0.001).Conclusion: The results of this study revealed that SBE has some beneficial effects on cardiac autonomic balance in T2DM patients.Bangladesh Soc Physiol. 2017, June; 12(1): 15-20

Predictors and diagnosis of cardiac autonomic nervous dysfunction in patients with type 1 and type 2 diabetes mellitus

Diabetic cardiovascular autonomic neuropathy (DCAN) is a diabetic complication characterised by early dissemination of sympathetic and parasympathetic, small-fibre neuronal degeneration. DCAN is the most dangerous and insidious complication that influences the clinical course and mortality rate of diabetes; however, it is often underestimated and not recognised by practitioners. Medical history and a physical examination are not sufficient for diagnosing DCAN. Laboratory diagnosis and the instrumental methods used to evaluate DCAN are time-consuming and not always available. Early detection of DCAN in diabetic patients is important for the early implementation of therapy. Today, there is no uniform diagnostic algorithm for DCAN in patients with various disorders of carbohydrate metabolism. This is due to the insufficient number of clinical trials and limitations of current protocols.&#x0D; This review presents an overview of the clinical and experimental studies of DCAN. The epidemiology, clinical manifestations, risk factors and underlying pathogenesis of DCAN are considered. The advantages and disadvantages of conventional and new diagnostic methods are discussed.

The Relationship between Cardiovascular Autonomic Dysfunction and Ocular Abnormality in Chinese T2DM.

Objective This study aims to explore the relationship between autonomic nerve dysfunction—assessed by cardiovascular autonomic neuropathy risk score (CAN-RS)—and ocular abnormality in Chinese type 2 diabetes mellitus (T2DM). Method This is a cross-sectional study. A total of 335 subjects with T2DM were enrolled. The state of visual acuity, the lens, the vitreous, and the fundus were tested by professional ophthalmic instruments. The electrochemical skin conductance (ESC) of the hands and feet was measured by SUDOSCAN, from which a cardiovascular autonomic neuropathy risk score (CAN-RS) was calculated. Receiver operating characteristic (ROC) curves were drawn to evaluate the feasibility and accuracy of CAN-RS in diabetic oculopathy screening. Results Abnormalities of the lens, vitreous, and fundus accounted for 7.8%, 5.1%, and 9.9%, respectively, in this study. The means of hands and feet ESC were higher than 60 μS, and CAN-RS was 33.1 ± 14.8%. In logistic regression analysis, CAN-RS was positively associated with lens (OR = 1.055, P < 0.001) and vitreous (OR = 1.044, P < 0.01) abnormality. The area under ROC to detect lens and vitreous abnormality was 0.713 and 0.725, respectively. Conclusion CAN-RS, a cardiac autonomic nerve dysfunction index calculated by SUDOSCAN, may be a promising index for lens and vitreous abnormality screening in T2DM patients. Further studies are needed to confirm the conclusion.

Assessment of cardiac autonomic nerve function status in female with iron deficiency anemia

Iron deficiency anemia is considered as one of the major public health problem in Bangladesh. Cardiac autonomic nerve dysfunction may present in iron deficiency anemia which increases the risk and further complications of this disease. Assessment of heart rate variability (HRV) is a non-invasive technique to evaluate cardiac autonomic nerve function status. To assess the cardiac autonomic nerve function status by heart rate variability analysis, 100 female subjects with iron deficiency anemia aged 20-45 years were included in the study group. For comparison, age and sex matched 100 apparently healthy female were selected as control. The HRV parameters were recorded by a 4 active channels, Polyrite-D. Mean resting pulse rate, LF power, LF norm and LF/HF were significantly (p &lt;0.0001) higher and total power, HF power, HF norm were significantly (p &lt;0.0001) lower in subjects with iron deficiency anemia in comparison to those of control group. This study concludes that cardiac parasympathetic activity was reduced in female with iron deficiency anemia.Bangladesh Med J. 2014 Sep; 43 (3): 125-129

Cardiac autonomic nervous dysfunction detected by both heart rate variability and heart rate turbulence in prediabetic patients with isolated impaired fasting glucose.

Objective:Cardiac autonomic nervous dysfunction (CAND), a severe complication of diabetes, has also been shown to affect prediabetic patients. The role of isolated impaired fasting plasma glucose (IFG), a subtype of prediabetes, is not clear in the pathogenesis of CAND. The aim of this study was to examine the relationship between isolated IFG and cardiac autonomic function using heart rate variability (HRV) and heart rate turbulence (HRT) indices derived from 24-h Holter–electrocardiogram recordings.Methods:This observational, prospective, cross-sectional study examined 400 consecutive subjects divided into three groups according to oral glucose tolerance test results: the control group [Group I, fasting plasma glucose (FPG) <100 mg/dL and normal glucose tolerance, n=193], the isolated IFG group (Group II, FPG ≥100 and <126 mg/dL, n=134), and the isolated impaired glucose tolerance (IGT), both IFG and IGT, or newly diagnosed diabetes’ group (Group III, n=73). Patients with non-sinus rhythm, known diabetes mellitus, coronary artery disease, heart failure, severe valvular disease, or receiving medical therapy that may affect HRV and HRT indices were excluded. Time domain HRV parameters, turbulence onset (TO), turbulence slope (TS), and HRT category were examined. Chi-square, one-way analysis of variance, Kruskal–Wallis H, and Mann–Whitney U tests were used to compare variables where appropriate. The correlation between Holter data and FPG levels was analyzed using the Spearman’s test. Multiple linear regression analysis was performed to identify independent predictors of the HRV and HRT parameters.Results:Median (interquartile range 25–75) FPG levels in Groups I, II, and III were 89 (83/93) mg/dL, 109 (104/116) mg/dL, and 174 (150.5/197) mg/dL, respectively. There were significant differences in HRV and HRT parameters between and among all groups. While HRV parameters and TS decreased from Group I to Group III, TO and HRT category gradually increased. Additionally, FPG level was significantly correlated with SDNN, r=–0.220; SDNN index, r=–0.192; SDANN, r=–0.207; RMSSD, r=–0.228; pNN50, r=–0.226; TO, r=0.354; and TS, r=–0.331 (all p<0.001).Conclusion:CAND, as detected by both HRV and HRT, appear to be present in the isolated IFG subtype of prediabetes.

Analysis of Heart Rate Variability and Cardiac Autonomic Nerve Remodeling in Streptozotocin-induced Diabetic Rats.

Diabetes mellitus (DM) is associated with both cardiovascular and autonomic nervous system dysfunction. Spectral analysis of heart rate variability (HRV) can be used to monitor changes in response to autonomic innervation and stimulation of the heart. In this study, conducted in a rat model of diabetes, HRV and changes in associated neurotransmitters and neurotrophic factors in the right atrium (RA) were monitored. Diabetes was induced by streptozotocin (STZ) (60 mg/kg) in male Wistar rats, and HRV data were collected for 10 weeks by telemetry. Time and frequency domains of HRV data were analyzed using established metrics. The levels of various neural enzymes in the RA were determined by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence to characterize autonomic nerve remodeling. Insulin and methycobal were used to block the effects of STZ. HRV parameters reflecting parasympathetic tone (SDNN, RMSSD and HF domains) sharply decreased in the first 3 weeks after STZ administration; measures of sympathetic tone (SDANN) increased. After a series of adjustments, cardiac autonomic nerve innervation reached a new equilibrium, with a dominance of sympathetic tone. RA levels of tyrosine hydroxylase (TH) increased, and choline acetyltransferase (ChAT) decreased, indicating autonomic nerve remodeling. Levels of growth associated protein-43 (GAP43) and nerve growth factor (NGF) increased during the period of diabetes-induced cardiac-nerve damage; however, the level of ciliary neurotrophic factor (CNTF) decreased. The physical condition and indexes of rats were normalized in different degree after administration of the insulin and methycobal, but not completely recovered. STZ-induced diabetes was associated with cardiac autonomic nerve dysfunction at both the organ and molecular levels. Parasympathetic nerves exhibited severe damage and/or weak recovery; remodeling of sympathetic nerves predominated during 10-weeks of STZ-induced diabetes.

Differential Patterns and Determinants of Cardiac Autonomic Nerve Dysfunction during Endotoxemia and Oral Fat Load in Humans.

The autonomic nervous system (ANS) plays an important role in regulating the metabolic homeostasis and controlling immune function. ANS alterations can be detected by reduced heart rate variability (HRV) in conditions like diabetes and sepsis. We determined the effects of experimental conditions mimicking inflammation and hyperlipidemia on HRV and heart rate (HR) in relation to the immune, metabolic, and hormonal responses resulting from these interventions. Sixteen lean healthy subjects received intravenous (i.v.) low-dose endotoxin (lipopolysaccharide [LPS]), i.v. fat, oral fat, and i.v. glycerol (control) for 6 hours, during which immune, metabolic, hormonal, and five HRV parameters (pNN50, RMSSD, low-frequency (LF) and high-frequency (HF) power, and LF/HF ratio) were monitored and energy metabolism and insulin sensitivity (M-value) were assessed. LPS infusion induced an increase (AUC) in HR and LF/HF ratio and decline in pNN50 and RMSSD, while oral fat resulted in elevated HR and a transient (hours 1-2) decrease in pNN50, RMSSD, and HF power. During LPS infusion, ΔIL-1ra levels and ΔIL-1ra and ΔIL-1ß gene expression correlated positively with ΔLF/HF ratio and inversely with ΔRMSSD. During oral fat intake, ΔGLP-1 tended to correlate positively with ΔHR and inversely with ΔpNN50 and ΔRMSSD. Following LPS infusion, lipid oxidation correlated positively with HR and inversely with pNN50 and RMSSD, whereas HRV was not related to M-value. In conclusion, suppression of vagal tone and sympathetic predominance during endotoxemia are linked to anti-inflammatory processes and lipid oxidation but not to insulin resistance, while weaker HRV changes in relation to the GLP-1 response are noted during oral fat load.Trial RegistrationClinicalTrials.gov NCT01054989

Increased prevalence of cardiac autonomic dysfunction at different degrees of glucose intolerance in the general population: the KORA S4 survey.

Cardiac autonomic nervous dysfunction (CAND) raises the risk of mortality, but the glycaemic threshold at which it develops is unclear. We aimed to determine the prevalence of, risk factors for and impact of CAND in glucose intolerance and diabetes. Among 1,332 eligible participants aged 55-74years in the population-based cross-sectional KORA S4 study, 130 had known diabetes mellitus (k-DM), and the remaining 1,202 underwent an OGTT. Heart rate variability (HRV) and QT variability were computed from supine 5min ECGs. In all, 565 individuals had normal glucose tolerance (NGT), 336 had isolated impaired fasting glucose (i-IFG), 72 had isolated impaired glucose tolerance (i-IGT), 151 had combined IFG-IGT (IFG-IGT) and 78 had newly detected diabetes mellitus (n-DM). Adjusted normal HRV limits were defined in the NGT population (5th and 95th percentiles). Three HRV measures were more frequently abnormal in those with k-DM, n-DM, IFG-IGT and i-IFG than in those with NGT (p < 0.05). The rates of CAND (≥2 of 4 HRV indices abnormal) were: NGT, 4.5%; i-IFG, 8.1%; i-IGT, 5.9%; IFG-IGT, 11.4%; n-DM, 11.7%; and k-DM, 17.5% (p < 0.05 vs NGT, except for i-IGT). Reduced HRV was associated with cardiovascular risk factors used to construct a simple screening score for CAND. Mortality was higher in participants with reduced HRV (p < 0.05 vs normal HRV). In the general population aged 55-74years, the prevalence of CAND is increased not only in individuals with diabetes, but also in those with IFG-IGT and, to a lesser degree, in those with i-IFG. It is associated with mortality and modifiable cardiovascular risk factors which may be used to screen for diminished HRV in clinical practice.

Time domain measures of heart rate variability to assess cardiac autonomic nerve function in female with iron deficiency anemia

Iron deficiency anemia is considered as one of the major public health problem in Bangladesh. Cardiac autonomic nerve dysfunction may present in iron deficiency anemia which increases the risk and further complications of this disease. Assessment of heart rate variability (HRV) is a non-invasive technique to evaluate cardiac autonomic nerve function status. To assess the cardiac autonomic nerve function status by heart rate variability analysis in female with iron deficiency anemia. This cross sectional study was conducted in the Department of Physiology, Dhaka Medical College, Dhaka from July 2012 to June 2013. For this, 100 female subjects with iron deficiency anemia aged 20-45 years were included in the study group (Group B). The anemic subjects were selected from Outpatient Department of Haematology in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. They were included in the study group on the basis of their pre-performed hemoglobin percentage, total count of RBC and serum ferritin level. Data were collected in pre-designed structured questionnaire by the researcher herself. For comparison, age and sex matched 100 apparently healthy female were selected as control (Group A) by personal contact from the different areas of Dhaka city. Analysis of HRV parameters were done in Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. The HRV parameters were recorded by a 4 active channels, Polyrite-D.For statistical analyses, unpaired Student’s t-test and Pearson’s correlation coefficient test were performed by using SPSS (version-19) as applicable. Mean resting pulse rate and mean heart rate were significantly (p &lt;0.0001) higher in subjects with iron deficiency anemia in comparison to those of control group. Hemoglobin concentration, total count of RBC, mean R-R interval, SDNN and RMSSD were significantly (p &lt;0.0001) lower in subjects with iron deficiency anemia in comparison to those of healthy control. This study concludes that cardiac parasympathetic activity was reduced in female with iron deficiency anemia.DOI: http://dx.doi.org/10.3329/bjpp.v30i1.20779 Bangladesh J Physiol Pharmacol 2014; 30(1):1-5

English

BACKGROUND AND OBJECTIVES: Cardiovascular autonomic nervous dysfunction has been demonstrated to severely debilitate HIV infected patients, namely by postural hypotension and syncopes It has important implication in health care of HIV patients. METHODS: 50 patients (25 HIV +ve without AIDS and 25 HIV+ with AIDS) who fulfilled the inclusion and exclusion criteria and 50 healthy matched controls were enrolled in the study. Autonomic function was assessed by batteries of autonomic function tests. RESULTS: In the present study 16% of HIV +ve with the AIDS had abnormal autonomic dysfunction and 4% of HIV positive without AIDS had abnormal autonomic dysfunction. Abnormalities in autonomic function occurred at all levels of CD4 counts. More number of abnormal results was found below 200 CD4 range. But the difference was not statistically significant. CONCLUSION: Cardiac autonomic nervous dysfunction is a common and relevant clinical problem it is significantly affected in both HIV positive without AIDS and HIV positive with AIDS groups. It may provide an alternative explanation for symptoms commonly observed in HIV infected individuals such as bowel and bladder dysfunction, impotence, syncope and sweating abnormalities.

Oxidative stress predicts progression of peripheral and cardiac autonomic nerve dysfunction over 6 years in diabetic patients.

Oxidative stress is implicated in the pathogenesis of experimental diabetic neuropathy, but prospective studies in diabetic patients are lacking. We aimed to evaluate whether the plasma levels of various biomarkers of oxidative stress predict the progression of diabetic neuropathy and mortality over 6 years. We followed 89 diabetic patients aged 54 ± 14 years (59 % with polyneuropathy), 72 of whom underwent nerve function reassessment after 6.2 ± 0.8 years, whereas 17 died after 4.2 ± 1.0 years. Plasma markers of oxidative stress at baseline included superoxide anion, hypochlorous acid, peroxynitrite, 8-iso-prostaglandin F2α, vitamin E/lipid ratio, and vitamin C. Neuropathy was assessed by symptoms and deficits, motor and sensory nerve conduction velocity (MNCV, SNCV), vibration perception thresholds (VPT), thermal detection thresholds, and heart rate variability (HRV). Despite a reduction in HbA1c by 1.4 ± 1.6 % (p < 0.001), median SNCV, sural SNCV, peroneal MNCV, malleolar VPT, and warm TDT deteriorated after 6 years (all p < 0.05). In multivariate models, increased superoxide generation was associated with a decline in median SNCV (β = -0.997; p = 0.036) and deterioration in HRV at rest (OR 1.63 [95 % CI 1.09-2.44]; p = 0.017) over 6 years. Low vitamin E/lipid ratio tended to predict a decrease in peroneal MNCV (β = 0.781; p = 0.057) and an increase in malleolar VPT (β = -0.725; p = 0.077). Plasma superoxide generation was associated with an increased risk of mortality (HR 23.2 [95 % CI 1.05-513]; p = 0.047). In conclusion, increased plasma superoxide generation predicted the decline in sensory and cardiac autonomic nerve function and mortality over 6 years in diabetic patients, but larger studies are required for confirmation.