Cardiovascular Reflexes Research Articles

INvesTigating the Abnormality of detrusor ConTractility by uroflowmetry in diabetic children (INTACT Trial): protocol of a prospective, observational study

IntroductionBladder emptying abnormalities and cardiovascular autonomic dysfunction are manifestations of autonomic dysfunction in people with diabetes mellitus (DM), which are major causes of morbidity and mortality. Since they can reduce...

Advanced glycation end-products are associated with diabetic neuropathy in young adults with type 1 diabetes.

Aims/hypothesisAdvanced glycation end-products (AGEs) may contribute to the development of diabetic neuropathy. In young adults with type 1 diabetes, we aimed to investigate the association between AGEs and cardiovascular autonomic neuropathy (CAN) and distal symmetric polyneuropathy (DSPN).MethodsThis cross-sectional study comprised 151 young adults. CAN was assessed by cardiovascular autonomic reflex tests; lying-to-standing test, deep breathing test (E/I), Valsalva manoeuvre, and heart rate variability indices; and the mean square of the sum of the squares of differences between consecutive R-R intervals and standard deviation of normal-to-normal intervals (SDNN), high- (HF) and low-frequency (LF) power, total frequency power, and the LF/HF ratio. DSPN was assessed by light touch, pain and vibration perception threshold (VPT), neuropathy questionnaires, and objective measures. AGEs were analysed in four groups using z-scores adjusted for relevant confounders and multiple testing: i) “glycolytic dysfunction”, ii) “lipid peroxidation”, iii) “oxidative stress”, and iv) “glucotoxicity”.ResultsA higher z-score of “glycolytic dysfunction” was associated with higher VPT (4.14% (95% CI 1.31; 7.04), p = 0.004) and E/I (0.03% (95% CI 0.01; 0.05), p = 0.005), “lipid peroxidation” was associated with higher LF/HF ratio (37.72% (95% CI 1.12; 87.57), p = 0.044), and “glucotoxicity” was associated with lower SDNN (−4.20% (95% CI −8.1416; −0.0896), p = 0.047). No significance remained after adjustment for multiple testing.Conclusions/interpretationsIn young adults with type 1 diabetes, increased levels of AGEs involving different metabolic pathways were associated with several measures of CAN and DSPN, suggesting that AGEs may play a diverse role in the pathogeneses of diabetic neuropathy.

Post-Acute Effect of SARS-CoV-2 Infection on the Cardiac Autonomic Function.

BackgroundRecent studies reported a long-lasting effect of COVID-19 infection that extends beyond the active disease and disrupts various body systems besides the respiratory system. The current study aims to investigate the post-acute effect of SARS-CoV-2 infection on cardiovascular autonomic activity, reactivity and sensitivity in patients who had the infection at least 3 months before.MethodsThis was a comparative cross-sectional observational study. Fifty-nine subjects were allocated into two groups, controls (n=31), who had no history of positive COVID-19 infection, and the post-COVID patients (n=28) who were recruited 3 to 8 months after testing positive for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR). Baseline cardiovascular autonomic activity was evaluated through recording of baseline heart rate variability (HRV), autonomic reactivity was determined through standard cardiovascular autonomic reflex tests (CART), and cardiac autonomic sensitivity was assessed through cardiac baroreceptor sensitivity (cBRS).ResultsHigher incidence of orthostatic hypotension was observed in post-COVID patients compared to controls (39.3% and 3.2%, respectively, p <0.001). Additionally, significantly reduced handgrip test, and heart rate response to head-up tilt was illustrated in the post-COVID group (p <0.001). About 85.7% of post-COVID participants had at least one abnormal cardiovascular reflex test (CART) compared to the control group (p <0.001). Although HRV parameters (TP, LF, HF, SDRR, RMSSD, pRR50), and the cBRS were numerically lower in the post-COVID-19 group, this did not reach the level of significance.ConclusionThe results of the present study are suggestive of altered cardiovascular reactivity in post-acute COVID patients and demand further investigation and longer term follow up.

Abstract 022: Impaired Parasympathetic Cardiac Modulation In Long-COVID Postural Tachycardia Syndrome

About 1 out of 10 patients infected with Sars-CoV2 have persistent symptoms beyond 4 weeks and some of them meet diagnostic criteria for postural tachycardia syndrome (Long-COVID POTS). The pathophysiology of Long-COVID POTS is unknown, but autonomic dysfunction may play a role. We hypothesize Long-COVID POTS patients have impaired cardiovascular autonomic reflexes and cardiac sympathovagal balance. We conducted a case-control study with patients recruited from the Vanderbilt Autonomic Dysfunction Center and an historical population of healthy controls. Hemodynamic parameters were measured before and during 75° head up tilt. Supine ECG and finger blood pressure were continuously measured for spontaneous heart rate variability analysis. The Low Frequency (0.04-0.15Hz, LF RR ) and High Frequency (0.15-0.4 Hz, HF RR ) oscillatory modulations of sino-atrial node discharge were computed. We included 14 Long-COVID POTS patients and 15 controls matched by age (34 ± 11 vs 28 ± 7; p=0.09) and BMI (26.1 ± 5.3 vs 23.0 ± 2.6; p=0.06). As expected, the orthostatic HR increase was higher in Long-COVID POTS compared to controls (40 ± 18 vs 21 ± 1, p&lt;0.05). Spectral analysis of heart rate variability in 9 patients and 15 controls (Figure) showed that Long-COVID POTS had reduced HF RR (363 ± 420 vs 933 ± 1000 ms 2 ; p&lt;0.05) and similar LF RR (798 ± 596 vs 962 ± 1075 ms 2 ; p=0.68), resulting in a greater LF/HF ratio (3.7 ± 2.9 vs 1.4 ± 1.3; p&lt;0.05). Patients with Long-COVID POTS have reduced markers of cardiovagal modulation, but normal cardiac sympathetic activation. Our results suggest that parasympathetic dysfunction contributes to the pathophysiology of Long-COVID POTS.

Cardiovascular Autonomic Neuropathy Is Associated With Increased Glucose Variability in People With Type 1 Diabetes.

We investigated the association between the cardiovascular autonomic neuropathy (CAN) diagnosis and glucose variability (GV) in type 1 diabetes (T1D), as autonomic dysfunction previously has been associated with increased GV. CAN was assessed by three recommended cardiovascular reflex tests (CARTs). Glucose metrics were obtained from 10-day blinded continuous glucose monitoring (CGM). Between-group differences in GV indices were assessed by regression analyses in 24 participants with T1D with CAN and 24 matched control subjects without CAN. The CAN diagnosis was associated with 4.9% (95% CI 1.0, 8.7) higher coefficient of variation (CV) (P = 0.014), 0.7 mmol/L (0.3, 1.1) higher SD (P = 0.002) of glucose, and 1.4 mmol/mol (0.0, 2.7) higher mean amplitude of glycemic excursions (P = 0.047). Lower measures of CARTs were associated with higher CV, SD, and time above range values. The CAN diagnosis associates with a significantly higher GV in T1D, despite a high prevalence of routine CGM use.

Cardiovascular autonomic function in chronic insomnia assessed by cardiovascular reflexes

Cardiovascular autonomic function in chronic insomnia assessed by cardiovascular reflexes

Mild hypoxia exposure impacts peripheral serotonin uptake and degradation in Gulf toadfish (Opsanus beta).

Plasma serotonin (5-hydroxytryptamine, 5-HT) homeostasis is maintained through the combined processes of uptake (via the 5-HT transporter SERT, and others), degradation (via monoamine oxidase, MAO) and excretion. Previous studies have shown that inhibiting SERT, which would inhibit 5-HT uptake and degradation, attenuates parts of the cardiovascular hypoxia reflex in gulf toadfish (Opsanus beta), suggesting that these 5-HT clearance processes may be important during hypoxia exposure. Therefore, the goal of this experiment was to determine the effects of mild hypoxia on 5-HT uptake and degradation in the peripheral tissues of toadfish. We hypothesized that 5-HT uptake and degradation would be upregulated during hypoxia, resulting in lower plasma 5-HT, with uptake occurring in the gill, heart, liver and kidney. Fish were exposed to normoxia (97.6% O2 saturation, 155.6 Torr) or 2min, 40min or 24 h mild hypoxia (50% O2 saturation, ∼80 Torr), then injected with radiolabeled [3H]5-HT before blood, urine, bile and tissues were sampled. Plasma 5-HT levels were reduced by 40% after 40 min of hypoxia exposure and persisted through 24 h. 5-HT uptake by the gill was upregulated following 2 min of hypoxia exposure, and degradation in the gill was upregulated at 40 min and 24 h. Interestingly, there was no change in 5-HT uptake by the heart and degradation in the heart decreased by 58% within 2 min of hypoxia exposure and by 85% at 24 h. These results suggest that 5-HT clearance is upregulated during hypoxia and is likely driven, in part, by mechanisms within the gill and not the heart.

Association between hypoglycaemic glucose variability and autonomic function in type1 diabetes with impaired hypoglycaemia awareness

Cardiovascular autonomic neuropathy (CAN) is suggested to underlie hypoglycaemic risk in impaired awareness of hypoglycaemia (IAH). We assessed the prevalence of CAN and the association between glucose variability (GV) and cardiovascular autonomic function in patients with type 1 diabetes (T1DM) and IAH.This study is a post-hoc-analysis of results obtained with the IN-CONTROL-trial, designed to assess the effects of continuous glucose monitoring (CGM) on glycaemia. Forty participants (aged 46.4 ± 11.4 years, diabetes duration 29.1 ± 13.5 years, HbA1c 7.5 ± 0.8%(58.2 ± 8.8 mmol/mol)) underwent 2-week blinded CGM measurements to obtain GV indices. Standardized cardiovascular reflex tests were used to determine the presence of CAN. Cardiovascular autonomic function was assessed with heart rate variability (HRV) measures.14(35%) participants were classified as having CAN. Participants with CAN had lower percentage time spent in hypoglycaemic range and low blood glucose index(LBGI). After correction for confounders, a significant positive association was found between the coefficient of variation (CV) or time spent in hypoglycaemic range and HRV measures SDRR or RMSSD, and between LBGI and RMSSD.In patients with T1DM and IAH, hypoglycaemic parameters were associated with better cardiovascular autonomic function and lower prevalence of CAN. This suggests that autonomic neuropathy does not seem to further deteriorate hypoglycaemic risk in patients with IAH.

Temporal Analysis of Sequential Changes in Heart Rate Variability During Non-hypotensive Hypovolemia.

Haemorrhage is associated with changes in the cardiac autonomic drive which begins during early stages of mild haemorrhage. The knowledge of chronology of the autonomic changes at smaller timescale during the period of haemorrhage can help identify the primary autonomic parameter which signals the institution of cardiovascular reflex mechanisms. To evaluate the heart rate variability in 2-min sequential segments with one minute overlap during and after the period of mild haemorrhage (450 ml) using blood donation as a model of acute blood loss. 47 male blood donors who had volunteered for blood donation were recruited for the study. Continuous lead II ECG was recorded before the start of the blood donation (5 min), during the period of the blood donation (~ 5-7 min) and after blood donation (5 min). The parasympathetic and sympathetic drive to heart was estimated by measures of heart rate variability in time and frequency domain. A significant decrease in the parameters assessing parasympathetic drive i.e., normalised High frequency (HFn) and NN50 (Number of pairs of adjacent NN intervals differing by more than 50 ms) and pNN50 (NN50 divided by the total number of all NN Intervals) was observed during blood donation at 3-5 min, as compared to baseline. An increase in parameters associated with sympathetic drive i.e., normalised low frequency (LFn) was observed only in the post donation period at 2-3 min. A significant rise in LF/HF ratio which is a marker of sympatho vagal balance was observed at 4-5 min during blood donation when compared to baseline. The initial cardiac autonomic change during mild haemorrhage is withdrawal of parasympathetic drive, followed by an increase in sympathetic tone which occurs much later.

Cardiovascular deconditioning increases GABA signaling in the nucleus tractus solitarii.

The nucleus tractus solitarii (nTS) is the major integrative brainstem region for autonomic modulation and processing of cardiovascular reflexes. GABA and glutamate are the main inhibitory and excitatory neurotransmitters, respectively, within this nucleus. Alterations in the GABA-glutamate regulation in the nTS are related to numerous cardiovascular comorbidities. Bedridden individuals and people exposed to microgravity exhibit dysautonomia and cardiovascular deconditioning that are mimicked in the hindlimb unloading (HU) rat model. We have previously shown in the nTS that HU increases glutamatergic neurotransmission yet decreases neuronal excitability. In this study, we investigated the effects of HU on nTS GABAergic neurotransmission. We hypothesized that HU potentiates GABA signaling via increased GABAergic release and postsynaptic GABA receptor expression. Following HU or control postural exposure, GABAergic neurotransmission was assessed using whole cell patch clamp whereas the magnitude of GABA release was evaluated via an intensity-based GABA sensing fluorescence reporter (iGABASnFR). In response to GABA interneuron stimulation, the evoked inhibitory postsynaptic current (nTS-IPSC) amplitude and area, as well as iGABASnFR fluorescence, were greater in HU than in control. HU also elevated the frequency but not the amplitude of spontaneous miniature IPSCs. Picoapplication of GABA produced similar postsynaptic current responses in nTS neurons of HU and control. Moreover, HU did not alter GABAA receptor α1 subunit expression, indicating minimal alterations in postsynaptic membrane receptor expression. These results indicate that HU increases GABAergic signaling in the nTS likely via augmented release of GABA from presynaptic terminals. Altogether, our data indicate GABA plasticity contributes to the autonomic and cardiovascular alterations following cardiovascular deconditioning (CVD).NEW & NOTEWORTHY Gravity influences distribution of blood volume and autonomic function. Microgravity and prolonged bed rest induce cardiovascular deconditioning (CVD). We used hindlimb unloading (HU), a rat analog for bed rest, to investigate CVD-induced neuroplasticity in the brainstem. Our data demonstrate that HU increases GABA modulation of nucleus tractus solitarii (nTS) neurons via presynaptic plasticity. Given the importance of nTS in integrating cardiovascular reflexes, this study provides new evidence on the central mechanisms behind CVD following HU.

458-P: Inflammatory Markers and Cardiovascular Autonomic Neuropathy in Type 1 Diabetes

Objective: We aimed to assess the role of chronic inflammation in the pathogenesis of cardiovascular autonomic neuropathy (CAN) , a serious complication of type 1 diabetes (T1D) . Methods: We leveraged an ongoing randomized, placebo-controlled clinical trial targeting inflammation with salsalate in individuals with T1D, to measure a panel of 40 inflammatory markers (Figure) in baseline samples. Measures of CAN included standardized cardiovascular autonomic reflex tests (CARTs) (E/I, Valsalva, 30/15 ratios) and indices of heart rate variability (HRV) . We used Spearman-rank to assess the correlations between inflammatory markers and CAN measures, and linear regression to adjust for age and hemoglobin A1c. Results: The Figure displays the correlation between biomarkers and CAN measures in 58 T1D participants (mean age 51 ± 13 years, and HbA1c 8.4 ± 1.8%) . Amongst all biomarkers, we noted a singular negative correlation between soluble urokinase plasminogen activator receptor (suPAR) and measures of CAN, which remained significant in multivariable analysis (E/I ratio p=0.005, Valsalva p=0.037, RFA p=0.019, LFA p=0.023) . Conclusion: Amongst a large panel of inflammatory markers, we found suPAR to have a notable association with CAN. SuPAR is an immune-mediated signaling glycoprotein which levels are strong predictors of risk in patients with diabetes, thus its role in CAN warrants further exploration. Disclosure L.Ang: None. L.Zhao: None. E.L.Feldman: None. S.Hayek: n/a. R.Pop-busui: Advisory Panel; Averitas Pharma, Inc., Boehringer Ingelheim International GmbH, Nevro Corp., Novo Nordisk, Reata Pharmaceuticals, Inc., Regenacy Pharmaceuticals, Inc. S.V.G.Gunaratnam: None. Y.Huang: None. K.R.Mizokami-stout: None. C.Martin: Advisory Panel; Nevro Corp. J.Reiss: n/a. A.Burant: None. A.Vasbinder: None. C.Launius: None. Funding NIH/NIDDK-1-R01-DK-107956-01

Exposure to Repeated Cold Stress Influences Sympathetic and Cardiovascular Responses to Muscle Stretch in Decerebrated Rats

Chronic stress is known to cause adverse physical and mental effects such as pain, chronic fatigue, and depression, and it is strongly related to many diseases and syndromes (e.g., fibromyalgia, chronic fatigue syndrome, and post‐traumatic stress disorder). Evidence suggests that exercise and physical activity in leisure time are effective in improving stress‐induced symptoms. Repeated cold stress (RCS), in which an animal is repeatedly exposed to alternating room and low temperatures, is one of the chronic stress models that induces chronic pain and depression. Mechanical hyperalgesia through thin muscle afferent fibers has also been reported to occur from RCS exposure. Since the muscle afferents have a dual modulatory function in nociception and cardiovascular reflex, we hypothesized that RCS augments the mechanical component of the exercise pressor reflex (the skeletal muscle mechanoreflex), i.e., skeletal muscle afferents‐mediated increases sympathetic nerve activity (SNA) and arterial blood pressure (AP).[Purpose]The purpose of this study was to clarify the impacts of RCS on sympathetic and cardiovascular responses to stimulation of the skeletal muscle mechanoreflex in decerebrated rats.[Methods]Male Sprague‐Dawley rats (body weight: 410 ± 15 g, age: 12 weeks) were exposed to RCS using a homemade automated RCS device. The rats were alternately moved to room temperature (22°C) and cold temperature (4°C) compartments at 30‐min intervals for 5 days. To assess the skeletal muscle mechanoreflex function, we measured mean AP (MAP), heart rate (HR), and renal SNA (RSNA) responses to 30‐s static passive stretching of the hindlimb muscles by in vivo recording from unanesthetized decerebrated rats. Stretching was performed by tracing the maximum tension curve obtained from 30‐s electrical stimulation. Changes (Δ) from baseline to peak values of the measured parameters between control and RCS rats were compared.[Results]Peak tension during the Achilles tendon stretch from baseline was not significantly different between groups (control: Δ929 ± 63 g [n = 6] vs RCS: Δ765 ± 66 g [n = 4], p = 0.17). Importantly, the peak RSNA response in RCS rats (Δ236.3% and Δ242.7%, n = 2) tended to be greater than that in control rats (Δ37.1% and Δ23.9%, n = 2). Moreover, RCS had a significantly (p &lt; 0.05) greater HR response (RCS: Δ3.7 ± 1.0 bpm [n = 4] vs control: Δ0.6 ± 0.5 bpm [n = 6]), and MAP response tended (P = 0.07) to be higher in the RCS group (Δ23 ± 6 mmHg, n = 4) than in the control group (Δ8 ± 4 mmHg, n = 6).[Conclusions]Our preliminary data demonstrate that RCS augments the skeletal muscle mechanoreflex. These results suggest that chronic stress can potentially cause exaggerated cardiovascular responses during physical activity.

Acute Chemogenetic Inhibition of Caudal NTS Astrocytes Reduced Systemic Blood Pressure in Rats Exposed to Chronic Intermittent Hypoxia‐mimicking Sleep Apnea Syndrome

Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, enhances carotid body (CB) discharges, leading to heightened sympathetic outflow and systemic hypertension. Previously, we found that CBs play a pivotal role in the hyperactivation of central nervous system (CNS) autonomic nuclei following CIH, particularly at the level of the caudal portion of the nucleus of the tractus solitary (NTS). Indeed, increased CB afferent activity during CIH increases the expression of pro‐inflammatory cytokines in the NTS, suggesting that CBs may drive neuroinflammation at key cardiorespiratory regulatory areas. Astrocytes has been implicated in inflammatory processes at the CNS. However, the contribution of NTS astrocytes on the cardiorespiratory abnormalities following CIH has not been studied. Accordingly, we assessed the role of astrocytes residing within the NTS on the maintenance of hypertension following CIH. Male Sprague‐Dawley rats (200 g) were exposed to CIH (5–6% inspired O2 for 20s, followed by room air for 280s, 12 times/h, 8 h/day, for 28 days). Arterial blood pressure (BP) was measured by indwelling telemetry. At 7 days of CIH exposure, rats were anesthetized and an adeno‐associated virus (AAV; 450 nL, 1*10‐12 vg) containing an inhibitory (Gi) Designer Receptor Exclusively Activated by Designer Drugs (DREADD) expressed under the control of the GFAP promoter was bilaterally injected into the caudal portion of the NTS using stereotaxic coordinates (–14.3 mm to bregma). At day 28 of CIH, hemodynamic and respiratory parameters were recorded before and after inhibition of NTS astrocytes with clozapine N‐oxide (CNO, 1mg/kg, ip.). At the end of the experiments rats were transcardially perfused with 4% buffered paraformaldehyde, brains extracted and sectioned to assess astrocyte activation within the NTS. Twenty‐eight days of CIH resulted in a significant 2‐fold increase in NTS astrocyte activation as evidenced by enhanced reactivity of GFAP. Additionally, resting BP was markedly elevated compared to Sham conditions (MABP, 98±2 vs. 84±2 mmHg, CIH vs. Sham; p&lt;0.05). Acute chemogenetic inhibition of NTS astrocytes following 28 days of CIH results in a significant reduction in BP (⁓10 mmHg; p&lt;0.05). In addition, the exacerbated hemodynamic response triggered by acute hypoxic stimulation (FiO2 10%) in rats exposed to CIH for 28 days was also reduced by NTS astrocyte inhibition ΔMABP, 30±2 vs. 15±2 mmHg, pre vs. post CNO; p&lt;0.05). No cardiovascular effects of CNO alone were found in control rats that did not underwent AAV‐DREADD‐Gi injection into the NTS. Taken together, our results support a role for NTS astrocyte activation on the maintenance of hypertension following chronic CIH and suggest that activation of NTS astrocytes may participate in the CB‐mediated cardiovascular reflex response during hypoxic stimulation.

Altered GABAergic neurotransmission at the nucleus tractus solitarii following Hindlimb Unloading

Hindlimb Unloading (HU) in rats induces dysautonomia and cardiovascular deconditioning (CVD) similar to that seen in bedridden individuals. The autonomic alterations in CVD and HU are related to plasticity within the central nervous system. The nucleus tractus solitarii (nTS) is a major integrative brainstem region for autonomic modulation and processing of cardiovascular reflexes. GABA and glutamate are the main inhibitory and excitatory neurotransmitters within this nucleus. HU increases nTS glutamatergic neurotransmission yet decreases neuronal excitability. In this study, we investigated the effects of HU on the GABAergic neurotransmission in the nTS. We hypothesized that HU increases GABA synaptic modulation of nTS neurons, which contributes to impaired autonomic and cardiovascular control. HU was induced by placing stainless wire rings in the tail of male Sprague‐Dawley rats (3 weeks old), and after one week of recovery suspending rats at an angle of 30–35° for two weeks with free access to food and water. Control animals were maintained in normal postural conditions. After HU or the control period, coronal brainstem slices were generated and whole‐cell patch clamp was performed to evaluate GABAergic neurotransmission in the nTS region. The magnitude of GABA release was evaluated via an intensity‐based GABA sensing fluorescence reporter (iGABASnFR). Block of GABAA receptors (Gabazine, 20µM and Bicuculline, 20µM) depolarized membrane potential in HU but not in Control, suggesting greater tonic GABA inhibition in HU. In response to GABA interneuron stimulation the evoked IPSC amplitude and area, as well as iGABASnFR fluorescence, was greater in HU than Control. HU also elevated the frequency of spontaneous miniature IPSCs but not their amplitude. Puffer application of GABA (100µM, 15ms) produced similar postsynaptic current responses in nTS neurons of HU and Control. These results indicate that HU increases GABAergic signaling in the nTS likely via augmented release of GABA from presynaptic terminals. This synaptic plasticity may be a component of the mechanisms underlying the autonomic and cardiovascular alterations following CVD.

Clinical manifestations and evaluation of cardiac autonomic neuropathy in diabetes mellitus and metabolic syndrome

A serious complication of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) is a dysfunction of the autonomic nervous system, which requires early evaluation for the effective treatment. The possibilities of pulse oximetry, which allows to assess heart rate variability in screening of autonomic nervous system dysfunction in patients with T2DM and MetS, have not yet been studied sufficiently.Objective: to evaluate the pulse oximetry effectiveness by comparing its results with the data of quantitative autonomic testing (QAT) to detect cardiac autonomic neuropathy (CAN) and clarify its degree in patients with T2DM and MetS.Patients and methods. The study included 30 patients with T2DM (mean age 63±7.9 years), 30 patients with MetS (mean age 61.5±9.1 years), 30 subjects from the control group (mean age 49.7±9.3 years). Patients underwent pulse oximetry, basic cardiovascular reflex tests, assessment of subjective sensations according to the NSC questionnaire, the severity of neurological deficit in the legs according to the NIS-LL scale and neuropathic pain syndrome according to the NTSS-9 scale.Results and discussion. In the group of patients with T2DM, severe CAN was detected in 13.3% of patients, moderate – in 40%. In the group of patients with MetS, severe CAN was detected in 10% of patients, moderate – also in 10%. In the control group, signs of moderate CAN were detected only in 3.3% of patients. The results of pulse oximetry tests with deep breathing were comparable to the QAT results (p&lt;0.001). Conclusion. Pulse oximetry can be used to diagnose CAN.

Qpack-a Python package for QASAT-quantitative scale for grading cerebral blood flow, autonomic testing, and skin biopsies.

Quantitative grading of testing has research and clinical relevance. QASAT (quantitative scale for grading of cardiovascular reflex tests, transcranial Doppler, sudomotor testing, and small fiber densities from skin biopsies) is an objective instrument for grading dysautonomia, related small fiber neuropathy and cerebral blood flow. QASAT uses established autonomic tests (deep breathing, Valsalva maneuver, tilt test, sudomotor test) and skin biopsies for assessment of small fibers. Calculations of scores are complex. This paper presents a qpack-an open source software package that implements QASAT in a Python programming language. The qpack automatically generates reproducible scores of each test and reduces calculation errors. Datasets for verifying the correct qpack implementation are provided. The goal of qpack is to facilitate availability, reproducibility, and quality of autonomic studies and skin biopsies for assessment of small fibers. Qpack is easy to use with standard Python distributions, can be incorporated into routine clinical or research autonomic testing and it is freely available.

Cardiac Autonomic Neuropathy in Patients with Newly Diagnosed Carbohydrate Disturbances.

Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus that can predispose patients to higher risk for cardiovascular death. The aim of the present study was to evaluate the presence of cardiac autonomic neuropathy and sudomotor dysfunction in patients with newly diagnosed carbohydrate disturbances (prediabetes or diabetes) and to assess their relationship to metabolic disturbances and cardiovascular risk. In the present study, we included 160 patients -78 with obesity without carbohydrate disturbances, 52 with prediabetes, and 30 with newly diagnosed diabetes. CAN was diagnosed using cardiovascular reflex tests and sudomotor function was evaluated by SUDOSCAN. Cardiovascular risk was calculated using SCORE and FRMINGHAM risk scores. The prevalence of cardiac autonomic neuropathy was significantly higher in patients with newly diagnosed diabetes. Independently of their glycemic status, the patients who had blood glucose on the 60th-minute of OGTT>8.5 mmol/l had significantly higher prevalence of cardiac autonomic neuropathy (30.2% vs 15.6%, р=0.044). Patients with high cardiovascular risk according to FRAMINGHAM and SCORE had worse heart rate variability scores. Autonomic neuropathy risk assessed by SUDOSCAN was a good predictor for the presence of CAN. In conclusion, CAN has a higher prevalence on patients with newly diagnosed diabetes compared to prediabetic and normoglycemic subjects, while the patients with blood glucose>8.5 mmol/l on the 60th-minute of OGTT have higher prevalence of CAN independently of their glycemic status. SUDOSCAN testing can be used to assess the risk of CAN and to select patients that should undergo further testing.

Thermal quantitative sensory testing as a screening tool for cardiac autonomic neuropathy in patients with diabetes mellitus.

IntroductionElectrophysiological diagnosis of cardiac autonomic neuropathy (CAN) is based on the evaluation of cardiovascular autonomic reflex tests (CARTs). CARTs are relatively time consuming and must be performed under standardized conditions. This study aimed to determine whether thermal quantitative sensory testing (TQST) can be used as a screening tool to identify patients with diabetes at a higher risk of CAN.MethodsEighty‐five patients with diabetes and 49 healthy controls were included in the study. Neurological examination, CARTs, TQST, biochemical analyses, and neuropathy symptom questionnaires were performed.ResultsCAN was diagnosed in 46 patients with diabetes (54%). CAN‐positive patients with diabetes had significantly higher warm detection thresholds (WDT) and significantly lower cold detection thresholds (CDT) in all tested regions (thenar, tibia, and the dorsum of the foot). CDT on the dorsum < 21.8°C in combination with CDT on the tibia < 23.15°C showed the best diagnostic ability in CAN prediction, with 97.4 % specificity, 60.9% sensitivity, 96.6% positive predictive value, and 67.3% negative predictive value.ConclusionTQST can be used as a screening tool for CAN before CART.

Autonomic cardiovascular reflex control of hemodynamics during exercise in heart failure with reduced ejection fraction and the effects of exercise training.

Heart failure with reduced ejection fraction is associated with increased exercise intolerance, morbidity, and mortality. Importantly, exercise intolerance in heart failure with reduced ejection fraction is a key factor limiting patient quality of life and survival. Exercise intolerance in heart failure with reduced ejection fraction stems from a multi-organ failure to maintain homeostasis at rest and during exercise, including the heart, skeletal muscle, and autonomic nervous system, lending itself to a system constantly trying to "catch-up". Hemodynamic control during exercise is regulated primarily by the autonomic nervous system, whose operation, in turn, is partly regulated via reflexive information from exercise-stimulated receptors throughout the body (e.g., arterial baroreflex, central and peripheral chemoreceptors, and the muscle metabo- and mechanoreflexes). Persons with heart failure with reduced ejection fraction exhibit malfunctioning autonomic reflexes, which lead to exaggerated sympathoexcitation and attenuated parasympathetic tone. Chronic elevation of sympathetic activity is associated with increased morbidity and mortality. In this review, we provide an overview of how each main exercise-related autonomic reflex is changed in heart failure with reduced ejection fraction, and the role of exercise training in attenuating or reversing the counterproductive changes.

Study of Autonomic Neuropathy in Cardiovascular System in Chronic Renal Failure Patients on Maintenance Hemodialysis

Autonomic nervous system abnormalities are major causes of morbidity and mortality in patients with chronic renal failure (CRF) on hemodialysis and are generally considered a part of polyneuropathy. Postural hypotension, impotency, gastrointestinal disturbance, gastrointestinal motility, and sweating abnormalities are common symptoms. The most frequent complication in patients with CRF on hemodialysis is intradialytic hypotension, and it has been suggested that intradialytic hypotension is mostly related to autonomic neuropathy. The pathogenesis of autonomic neuropathy is unclear, but a reduced response to norepinephrine by the end organ and the toxic effect of metabolic toxins are considered to be some of the causes. Five cardiovascular reflex tests are generally used to determine autonomic neuropathy: the heart rate reaction to the Valsalva Maneuver, the heart rate variability during deep breathing, the heart rate response to standing up, the blood pressure response to standing up, and the blood pressure response to hand grip exercise.