Cardiovascular Reflexes Research Articles

Normative data on measures of cardiovascular autonomic neuropathy and the effect of pretest conditions in a large Danish non-diabetic CVD-free population from the Lolland-Falster Health Study.

Cardiovascular autonomic neuropathy (CAN) is a common diabetic complication associated with excess morbidity and mortality. CAN is also seen in conditions such as Parkinson's disease. Normative reference data for cardiovascular autonomic function are used to stratify individuals into those with and without CAN. However, reference thresholds for both cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV) are scarce and based on small sample sizes. The aim of the study was to establish contemporary normative reference thresholds based on a large non-diabetic population free of cardiovascular disease (CVD). Cardiovascular autonomic function, CARTs and 5-min HRV indices were assessed in individuals without diabetes and CVD from the Lolland-Falster Health Study (2018-2020) by applying the point-of-care device Vagus™. Age-specific normative reference thresholds were estimated by using log-transformed quantile regression models at the 5th and 10th percentile, with adjustments made for sex. Models assessing the association between age and HRV indices were further adjusted for heart rate. We present age-specific normative reference thresholds for cardiovascular autonomic function, including CARTs and HRV, for 875 individuals (48% females) aged 15-85years. The reference thresholds are presented for both the 5th and 10th lower percentile. Higher age was inversely associated with all outcomes. Females tended to have a higher parasympathetic drive compared to males. Pre-test conditions did not affect CARTs significantly. The presented age-related normative reference thresholds for both CARTs and HRV indices based on a large Danish cohort may facilitate improved quality of research and treatment.

Low muscle strength rather than low muscle mass is associated with cardiovascular autonomic neuropathy in patients with type 2 diabetes

Several studies have investigated whether sarcopenia is associated with diabetic microvascular complications, but very few have examined associations between sarcopenia and cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM). Therefore, we investigated associations of muscle strength (handgrip strength [HGS]) and mass (appendicular skeletal muscle mass index [ASMI]) and CAN in patients with T2DM. We enrolled 342 patients in this retrospective, cross-sectional study. Cardiovascular reflex tests were used to assess CAN according to Ewing’s protocol. Relative HGS was determined after normalizing absolute HGS to body weight (HGS/body weight [kg]). We defined low HGS and low ASMI according to a consensus report of the Asian Group for Sarcopenia. Logistic regression analyses were carried out to assess the associations between relative HGS or ASMI quartiles and the presence of CAN in patients with T2DM. The prevalence rates of CAN, low HGS, and low ASMI in the study subjects were 34.8%, 17.3%, and 18.7%, respectively. Low HGS was significantly more prevalent in patients with CAN than those without CAN (23.5% vs. 13.9%, p = 0.025). The CAN scores were significantly and negatively correlated with relative HGS but not with ASMI. Relative HGS was negative correlated with age, glycated hemoglobin, fasting plasma glucose, hsCRP, body mass index, and HOMA-IR and positively correlated with ASMI. The prevalence of CAN gradually increased with decreasing quartile of relative HGS (28.4% in Q4, 31.8% in Q3, 34.2% in Q2, and 45.3% in Q1, p = 0.02 for trend). Multivariable-adjusted prevalence ratios (PRs) for CAN, determined by comparing the first, second, and third quartiles with the fourth quartile of relative HGS, were 4.4 with a 95% confidence interval (95% CI) of [1.1 to 17.3]), 2.3 (95% CI [0.8 to 6.9]), and 1.2 (95% CI [0.4 to 3.7]), respectively. The prevalence of CAN and the PRs (95% [CI]) for CAN based on ASMI were not statistically significant. Our findings suggest that low muscle strength rather than low muscle mass was significantly associated with the presence of CAN. Therefore, HGS testing could help identify patients who would benefit from screening for earlier diagnosis of CAN.

Cardiovascular Reflexes - Vagus as the Key Player.

The cardiac and vascular systems work in coordination by activating various reflex mechanisms based on the body's needs. These may be during physiological variations or pathophysiological changes seen in disease conditions of varying degrees of severity. This article intends to explain various reflexes involved in the homeostasis of the cardiovascular system and the role of vagus as the key component in all these reflexes. The article also explains the components of the reflex arc, the stimulus and response, and the role of reflex in a few diseases. This article describes 22 different cardiovascular reflexes in detail.

Prevalence of cardiovascular autonomic neuropathy in an admixed population of patients with type 1 diabetes. Lessons from a pioneer multicentre study in Brazil

AIMSTo evaluate the prevalence of cardiovascular autonomic neuropathy (CAN) and its associated factors in Brazilian patients with type 1 diabetes (T1D). MethodsThis cross-sectional, multicentre study was conducted in 14 public clinics in ten Brazilian cities. From 1760 patients, 1712 were included (97.3 %): 953 females (55.7 %), 930 (54.3 %) Caucasians, aged 29.9 ±11.9 years and with diabetes duration of 15.4 ± 9.2 years. CAN was evaluated using cardiovascular autonomic reflex tests. ResultsThe prevalence of CAN was 23.4 %. Multivariable hierarchical logistic regression showed CAN associated with age, smoking, lower socioeconomic status, higher yearly medical appointments, insulin therapeutic regimens, higher levels of HbA1c, total cholesterol, uric acid, diastolic blood pressure and heart rate, presence of retinopathy, diabetic kidney disease and a tendency to be associated with severe hypoglycemia. Lower health-related quality of life was also found in univariate analysis in these patients. ConclusionsPatients with T1D presented an important prevalence of CAN that was associated with other diabetes-related chronic complications, and also with demographic, clinical and laboratorial traditional risk factors. Considering lack of formal policy, our data could be used for guiding public health approach to awareness and CAN’s screening, diagnosis and clinical management in patients with T1D in Brazil.

The new face of diabetes mellitus — rhythm and conduction disorders

This review article is devoted to changes in heart rhythm against the background of type 2 diabetes mellitus, which is one of the most common endocrine diseases. In recent years, there has been an increasing association between type 2 diabetes mellitus and heart rhythm disorders. Arrhythmias such as tachycardia, bradycardia and atrial fibrillation are common in patients with type 2 diabetes and can have serious consequences on health and quality of life. Type 2 DM is increasingly common worldwide due to the rise in sedentary lifestyles, overweight, abdominal forms of obesity, and diets containing too much fat and carbohydrates. Insulin-independent diabetes is a metabolic disease responsible for autonomic neuropathy of the heart that affects both sympathetic and parasympathetic fibers, which can be explained by the adverse effect of blood glucose levels on heart rate variability (HRV). Although the gold standard is cardiovascular reflex tests to assess cardiovascular autonomic neuropathy, one of the most important is the measurement of heart rate variability (HRV). HRV is the variation between two consecutive contractions: the higher the variation, the higher the activity of the parasympathetic nervous system. A high HRV reflects the fact that a person can constantly adapt to changes in the microenvironment. Thus, low HRV is a marker of cardiovascular risk.

Cardiovascular Autonomic Modulation in Chronic Coronary Syndrome Following Percutaneous Coronary Intervention.

Introduction The risk of sudden death in patients with chronic coronary syndrome (CCS) is increased by unbalanced cardiovascular autonomic function. Since myocardial ischemia appears to be the causeof this condition of autonomic dysregulation, treating this condition should improve and correct the autonomic functions. Improving myocardial perfusion by PCI might have beneficial effects on the recovery of autonomic balance in ischemia-triggered autonomic dysregulation. Objective In the present study, autonomic modulation in patients with CCS was evaluated before and after percutaneous coronary intervention (PCI) using cardiovascular reflex tests. Methods A total of 30CCS patients were recruited from the cardiology outpatient department. The patients were tested withcardiovascular reflex tests (lying to standing, 30:15 ratio, Valsalva ratio, isometric handgrip test, and deep breathing test) before and after PCI. The licensed statistical software SPSS version 21.0 was used to compile and analyse the data. Results Out of 30 patients, parasympathetic reactivity tests conducted post-PCI were significantly higher as compared to pre-PCI patients: (1) lying to standing - 30:15 ratio (1.17± 0.102 versus 1.03± 0.064, p=0.000); (2) Valsalva ratio (1.42±0.276 versus 1.02±0.133, p=0.000), (3) delta heart rate in deep breathing test (17.23± 3.004 bpm versus 7.85± 4.076 bpm, p=0.000), and (4) expiration to inspiration (E:I) ratio (1.25± 0.050 versus 1.11± 0.064, p=0.000. Among sympathetic reactivity tests, lying to standing test for fall in systolic blood pressure was significantly higher in the pre-PCI state than post-PCI (-20.73± 10.29 versus -2.33± 7.67, p=0.000). The rise in DBP of the isometric handgrip test was significantly higher in post-PCI compared to pre-PCI patients (36.73±8.39 mm Hg versus 16.63±8.47 mm Hg, p=0.000). Conclusion Resting autonomic tone as determined by cardiovascular reflex testing reveals an increase in both parasympathetic and sympathetic reactivity following PCI in CCS, according to the findings of this preliminary study. As a result, we propose that noninvasive procedures like cardiovascular reflex tests be used to stratify the likelihood of illness development in the future.

Cardiovascular autonomic and peripheral sensory neuropathy in women with obesity.

A higher incidence of neural dysfunction in people with obesity has been described. We determined the prevalence of neuropathic lesions in obese women and evaluated their potential association with anthropometric and laboratory parameters. In our cross-sectional study, we enrolled female patients with obesity and without diabetes before obesity treatment. Voluntary female subjects were controls with a normal body mass index (BMI). Autonomic function was assessed by Ewing's cardiovascular reflex tests, while comprehensive peripheral neuropathic assessments were conducted utilizing the Neurometer®, Tiptherm®, Monofilament®, and Rydel-Seiffer tuning fork tests. Sudomotor function was assessed by the Neuropad®-test. Body composition was examined using the InBody 770. 71 patients (mean ± SD; age: 36.1 ± 8.3 years; BMI: 40.2 ± 8.5 kg/m2) and 36 controls (age: 36.4 ± 13.3 years; BMI: 21.6 ± 2.1 kg/m2) were enrolled. Patients had significantly higher systolic (patients vs. controls; 137.5 ± 16.9 vs. 114.6 ± 14.8 mmHg, p<0.001) and diastolic (83.0 ± 11.7 vs.69.8 ± 11.2 mmHg, p<0.001) blood pressure compared to controls. Among autonomic tests, only the heart rate response to Valsalva maneuver (Valsalva-ratio) revealed significant impairment in patients (1.4 ± 0.2 vs. 1.7 ± 0.4, p<0.001). Neurometer® at the median nerve revealed increased current perception threshold (CPT) values at all stimulating frequencies in patients (CPT at 2000Hz: 204.6 ± 70.9 vs. 168.1 ± 66.9, p=0.013; 250Hz: 84.4 ± 38.9 vs. 56.5 ± 34.8, p<0.001; CPT at 5Hz: 58.5 ± 31.2 vs 36.9 ± 29.1, p<0.001). The Rydel-Seiffer tuning fork test has revealed a significant impairment of vibrational sensing on the lower limb in patients (right hallux: 6.8 ± 0.9 vs. 7.4 ± 0.8, p=0.030; left hallux: 6.9 ± 0.8 vs. 7.3 ± 0.9, p=0.029). The Neuropad® testing showed a significant impairment of sudomotor function in women with obesity. A negative correlation was found in patients between BMI and the 25-hydroxy-D3/D2-vitamin levels (r=-0.41, p=0.00126) and a positive correlation between the BMI and resting systolic blood pressure (r=0.26, p=0.0325). Peripheral sensory neuronal and sudomotor function impairments were detected in female patients with obesity compared to the controls with normal BMI. Cardiovascular autonomic dysfunction was also revealed by the Valsalva-ratio in these patients, suggesting the presence of parasympathetic dysfunction. The negative correlation between BMI and the 25-hydroxy-D3/D2-vitamin highlights the potential deficiency of vitamin D in the population affected by obesity.

A Cross-Sectional Study of Cardiovascular Autonomic Reactivity in Ehlers-Danlos Syndrome.

Ehlers-Danlos syndrome (EDS) may be linked to dysfunction in the autonomic nervous system, affecting collagen production and processing. These collagen abnormalities lead to a condition called dysautonomia. Findings underscore the need for further investigation into autonomic nervous system function in EDS which involves larger studies to strengthen the evidence of non-invasive screening tools like cardiovascular reflex tests. These tests might offer a valuable way to assess an individual's risk for future complications. This study aimed to assess autonomic reactivity in EDS patients using cardiovascular reflex tests. This study was conducted at the Department of Physiology, Naraina Medical College and Research Centre, Kanpur (Uttar Pradesh). The cardiovascular reflex test was used to identify 60 individuals, 30 of whom were EDS patients and 30 were healthy controls, with a common age limit of 18-25 years. Cardiovascular reflex tests, such as the delta heart rate, lying-to-standing test (LST), deep breathing test (DBT), and Valsalva maneuver, were performed and recorded for each subject. IBM SPSS Statistics for Windows, Version 21.0 (Released 2012; IBM Corp., Armonk, New York, United States) was used for the compilation and analysis of data. The expiration-to-inspiration (E:I) ratio and delta heart rate of the EDS patients both significantly decreased as compared to the healthy control group (1.10±0.02 versus 1.22±0.77 and 14.03±0.31 versus 15.52±0.32). The Valsalva ratio of the EDS patients decreased (1.28±0.01) as compared to the healthy control group (1.46±0.01), which was statistically significant. The 30:15 ratio in the EDS patients was significantly decreasedcompared to the healthy control group (1.08±0.01 versus 1.15±0.01). The handgrip test and cold pressor test results were statistically insignificant. The study suggests a connection between EDS and autonomic nervous system dysfunction, causing symptoms like tachycardia and hypotension. It recommends exploring non-invasive cardiovascular reflex tests as a tool to identify autonomic dysfunction in EDS patients and predict long-term cardiovascular complications. These tests offer valuable insights into autonomic function.

Composite Autonomic Symptom Score-31 for the diagnosis of cardiovascular autonomic dysfunction in long-term coronavirus disease 2019.

Composite Autonomic Symptom Score-31 (COMPASS-31) is an easy-to-use screening tool for the evaluation of autonomic dysfunction in various diseases affecting neural function but has rarely been used in the assessment of long coronavirus disease 2019 (COVID-19). This study aimed to evaluate the diagnostic accuracy of the COMPASS-31 score in detecting dysfunction of the autonomic nervous system in patients 3 months after COVID-19 infection. Fifty-nine subjects were recruited and grouped into 2: (a) controls (n = 31) who had never had positive polymerase chain reaction results for COVID-19 before and (b) the post-COVID-19 patients (n = 28) who had confirmed COVID-19 infection 3-6 months before recruitment. COMPASS-31 questionnaire was utilized to evaluate subjective symptoms or evidence of autonomic dysfunction. Autonomic dysfunction was assessed objectively by cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV). For comparison of quantitative variables between two groups, t-test or Mann-Whitney U test, as appropriate, were used. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), negative likelihood ratio (LR), and positive LR were used as measures of diagnostic accuracy. Receiver operating characteristic (ROC) curve analysis determined the overall accuracy of COMPASS-31. The median COMPASS score was found to be significantly higher in post-COVID-19 participants than controls (15.5 vs. 10, P = 0.021). The median total CART score was also significantly higher in post-COVID-19 participants (0 vs. 1, P < 0.001). Out of 6 domains of the COMPASS score, the median value for orthostatic dysfunction was found to be significantly higher in post-COVID-19 participants than controls (12 vs. 0, P = 0.008). There was significantly fair accuracy of the COMPASS score with an area under the receiver operating curve 0.68 (0.54-0.82) following the total CART score ≥2 as the gold standard in the diagnosis of autonomic dysfunction (P = 0.021). The best cutoff point of the total COMPASS score was 12.5, where the optimal values of sensitivity, specificity, and positive and negative predictive values were achieved. Nonsignificant and weak correlations between CARTs, HRV parameters, and COMPASS score were found. COMPASS-31 could be used as a user-friendly screening tool to detect autonomic dysfunction in post-COVID-19 cases with acceptable sensitivity and specificity.

Determinants of Orthostatic Hypotension in Type 2 Diabetes: Is Cardiac Autonomic Neuropathy the Main Factor?

ObjectivesTo evaluate the determinants of orthostatic hypotension (OH) in type 2 diabetes (T2D) and the usefulness of Δheart rate (HR)/Δsystolic blood pressure (SBP), index of cardiac baroreflex function, in identifying neurogenic OH. MethodsIn 208 participants with T2D, we diagnosed early cardiovascular autonomic neuropathy (CAN) and confirmed CAN according to 1 and 2 HR-based cardiovascular reflex tests (HR-CARTs). Through OH test we defined OH as SBP falls of ≥20 and ≥30 mm Hg with supine SBPs of <140 and ≥140 mm Hg, respectively. In participants with OH, we used the lying-to-standing and OH test and its diagnostic accuracy for neurogenic OH (as OH plus confirmed HR-CAN). ResultsOH was present in 25 participants and associated with lower HR-CART scores, higher glycosylated hemoglobin level, the presence of CAN, retinopathy, and peripheral vascular disease, the absence of hypertension, and physical activity (all, P < .05) but not with interfering drugs and β-blockers. In a multiple logistic regression, HR-CAN was the main determinant of OH (odds ratio, 4.74) with physical activity and hypertension (odds ratios, 0.16 and 0.23; R2 = 0.22). ΔHR/ΔSBP had a good diagnostic accuracy for neurogenic OH (area under the receiver operating characteristic curve, 0.816 ± 0.087) and, at the cutoff of 0.5 bpm/mm Hg, a sensitivity of 100% and specificity of 63.2%. ConclusionCAN remains the primary determinant of OH in T2D but does not explain all its variance. The index ΔHR/ΔSBP may represent a useful clinical tool to identify neurogenic OH.

Cardiac Autonomic Neuropathy in Graves' Disease: Smoking and Age as Predictive Factors

ObjectivesHypermetabolic state in Graves' disease (GD) has a great impact on heart homeostasis, acting directly on the heart muscle and modulating the autonomic nervous system. To characterize cardiac autonomic neuropathy (CAN) as a possible complication in patients with GD. MethodsWe evaluated euthyroid GD patients and a control group of healthy euthyroid people. CAN was assessed using autonomic tests of cardiovascular reflex and heart rate variability: respiratory, Valsalva, orthostatic and orthostatic hypotension tests, high frequency, low frequency, and very low-frequency bands. Transthoracic echocardiography was performed in GD patients. ResultsSixty GD patients and 50 people in control group were assessed. CAN was diagnosed in 20% of GD and 14% in the control group. Among GD, 13.3% presented incipient, and 6.7% established CAN, while in the control group, it was verified incipient in 8% and established in 6% (P = .7479). All GD patients with CAN presented an alteration in the deep breathing test. Age and smoking were evidenced as factors associated with the presence of CAN, while higher TRAb values at diagnosis decreased the chance of CAN. ConclusionsThe prevalence of CAN in euthyroid GD patients was 20%. Changes in the cardiac autonomic nervous system were identified, pointing to the importance of evaluating this complication in these patients. Smoking was a predictive factor for CAN, increasing its relationship with conditions that aggravate GD.

The Relationship between the Ewing Test, Sudoscan Cardiovascular Autonomic Neuropathy Score and Cardiovascular Risk Score Calculated with SCORE2-Diabetes.

Background and Objectives: Cardiac autonomic neuropathy (CAN) is a severe complication of diabetes mellitus (DM) strongly linked to a nearly five-fold higher risk of cardiovascular mortality. Patients with Type 2 Diabetes Mellitus (T2DM) are a significant cohort in which these assessments have particular relevance to the increased cardiovascular risk inherent in the condition. Materials and Methods: This study aimed to explore the subtle correlation between the Ewing test, Sudoscan-cardiovascular autonomic neuropathy score, and cardiovascular risk calculated using SCORE 2 Diabetes in individuals with T2DM. The methodology involved detailed assessments including Sudoscan tests to evaluate sudomotor function and various cardiovascular reflex tests (CART). The cohort consisted of 211 patients diagnosed with T2DM with overweight or obesity without established ASCVD, aged between 40 to 69 years. Results: The prevalence of CAN in our group was 67.2%. In the study group, according SCORE2-Diabetes, four patients (1.9%) were classified with moderate cardiovascular risk, thirty-five (16.6%) with high risk, and one hundred seventy-two (81.5%) with very high cardiovascular risk. Conclusions: On multiple linear regression, the SCORE2-Diabetes algorithm remained significantly associated with Sudoscan CAN-score and Sudoscan Nephro-score and Ewing test score. Testing for the diagnosis of CAN in very high-risk patients should be performed because approximately 70% of them associate CAN. Increased cardiovascular risk is associated with sudomotor damage and that Sudoscan is an effective and non-invasive measure of identifying such risk.

ST-2560, a selective inhibitor of the NaV1.7 sodium channel, affects nocifensive and cardiovascular reflexes in non-human primates.

The voltage-gated sodium channel isoform NaV1.7 is a high-interest target for the development of non-opioid analgesics due to its preferential expression in pain-sensing neurons. NaV1.7 is also expressed in autonomic neurons, yet its contribution to involuntary visceral reflexes has received limited attention. The small molecule inhibitor ST-2560 was advanced into pain behaviour and cardiovascular models to understand the pharmacodynamic effects of selective inhibition of NaV1.7. Potency of ST-2560 at NaV1.7 and off-target ion channels was evaluated by whole-cell patch-clamp electrophysiology. Effects on nocifensive reflexes were assessed in non-human primate (NHP) behavioural models, employing the chemical capsaicin and mechanical stimuli. Cardiovascular parameters were monitored continuously in freely-moving, telemetered NHPs following administration of vehicle and ST-2560. ST-2560 is a potent inhibitor (IC50 = 39 nM) of NaV1.7 in primates with ≥1000-fold selectivity over other isoforms of the human NaV1.x family. Following systemic administration, ST-2560 (0.1-0.3 mg·kg-1, s.c.) suppressed noxious mechanical- and chemical-evoked reflexes at free plasma concentrations threefold to fivefold above NaV1.7 IC50. ST-2560 (0.1-1.0 mg·kg-1, s.c.) also produced changes in haemodynamic parameters, most notably a 10- to 20-mmHg reduction in systolic and diastolic arterial blood pressure, at similar exposures. Acute pharmacological inhibition of NaV1.7 is antinociceptive, but also has the potential to impact the cardiovascular system. Further work is merited to understand the role of NaV1.7 in autonomic ganglia involved in the control of heart rate and blood pressure, and the effect of selective NaV1.7 inhibition on cardiovascular function.

Exploring Cardiovascular Autonomic Function before and after Chronic Deep Brain Stimulation in Parkinson's Disease.

Blood pressure control in Parkinson's disease (PD) under subthalamic deep brain stimulation (STN-DBS) is influenced by several intertwined aspects, including autonomic failure and levodopa treatment. To evaluate the effect of chronic STN-DBS, levodopa, and their combination on cardiovascular autonomic functions in PD. We performed cardiovascular reflex tests (CRTs) before and 6-months after STN-DBS surgery in 20 PD patients (pre-DBS vs. post-DBS). CRTs were executed without and with medication (med-OFF vs. med-ON). CRT results and occurrence of neurogenic orthostatic hypotension (OH) did not differ between pre- and post-DBS studies in med-OFF condition. After levodopa intake, the BP decrease during HUTT was significantly greater compared to med-OFF, both at pre-DBS and post-DBS evaluation. Levodopa-induced OH was documented in 25% and 5% of patients in pre-DBS/med-ON and post-DBS/med-ON study. Chronic stimulation did not influence cardiovascular responses, while levodopa exerts a relevant hypotensive effect. The proportion of patients presenting levodopa-induced OH decreases after STN-DBS surgery.

Effect of Lower Body Negative Pressure (LBNP) on Blood Pressure in Awake Rats and Effects of Anesthesia

Lower body negative pressure (LBNP) has been used for decades in a variety of settings and species to model orthostatic challenge (OC) and baroreceptor unloading. However, due to physical constraints, measurements of blood pressure (BP) during LBNP have always been made in anesthetized animals, where cardiovascular reflexes are blunted or even blocked. In terminal procedures, for example, urethane is often used in an attempt to preserve some measure of autonomic reflex function during OC. More recently, investigators have used isoflurane in animals fitted with BP telemeters in order to perform longitudinal studies, but the extent to which various cardiovascular reflexes may be preserved is unknown. Here we have developed a novel method to apply lower body negative pressure in awake rats instrumented for BP measurement. Rats were placed into a tubular restraining device (5 cm diameter X 21 cm length), that is divided into an upper and lower chamber by two adjacent latex septa with small holes (~ 2 cm). Rats were positioned so that the septa form a seal at the lower margin of the thorax, thereby creating independent upper and lower chambers. Negative pressure was then applied to the lower chamber using a high-volume vacuum and the pressure controlled using an adjustable damper. BP measurements in response to progressive levels of LBNP (-3 to -15 mmHg) were first made in awake rats, followed by induction of anesthesia and repetition of the LBNP protocol. The effects of pentobarbital (50mg/kg), ketamine/xylazine (70/6 mg/kg) and isoflurane (3%) were determined on separate days. BP and heart rate (HR) responses are shown in the Table. We found that BP was remarkably preserved in awake rats up to at least -9 mmHg LBNP, and thereafter (at -12 and -15 mmHg) decreased modestly. There was a robust baroreceptor-mediated increase in HR beginning at -6 mmHg. By contrast, under each anesthetic, blood pressure decreased dramatically and progressively with increasing LBNP, and the reflex increases in HR were entirely blocked (and actually inverted). These data indicate that the awake rat has robust mechanisms to preserve cardiovascular function during OC, and that these mechanisms are severely compromised during anesthesia. University of Cincinnati College of Medicine Innovation Seed Grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Contemporary prevalence of diabetic neuropathies in individuals with type 1 and type 2 diabetes in a Danish tertiary outpatient clinic

BackgroundPopulation-based prevalence estimates of distal symmetric polyneuropathy (DPN) and diabetic autonomic neuropathy (DAN) are scares. Here we present neuropathy estimates and describe their overlap in a large cohort of people with type 1 and type 2 diabetes. MethodsIn a large population of outpatient participants, DPN was assessed using vibration perception threshold, sural nerve function, touch, pain and thermal sensation. Definite DPN was defined by the Toronto Consensus Criteria. Painful DPN was defined by Douleur Neuropathique 4 Questions. DAN measures were: cardiovascular reflex tests, electrochemical skin conductance, and gastroparesis cardinal symptom index. ResultsWe included 822 individuals with type 1 (mean age (±SD) 54 ± 16 years, median [IQR] diabetes duration 26 [15–40] years) and 899 with type 2 diabetes (mean age 67 ± 11 years, median diabetes duration 16 [11−22] years).Definite DPN was prevalent in 54 % and 68 %, and painful DPN was in 5 % and 15 % of type 1 and type 2 participants, respectively. The prevalence of DAN varied between 6 and 39 % for type 1 and 9–49 % for type 2 diabetes. DPN without other neuropathy was present in 45 % with T1D and 50 % with T2D. ConclusionThe prevalence of DPN and DAN was high. DPN and DAN co-existed in only 50 % of cases.

Autonomic function and specific right atrial functions - Is there a relationship? Correlations from the three-dimensional speckle-tracking echocardiographic MAGYAR-Healthy Study.

Similarly to the ventricles, the atria are under sympathetic/parasympathetic neural regulation. Accordingly, correlations were investigated between Ewing's standard cardiovascular reflex tests (SCRTs) and three-dimensional speckle-tracking echocardiography (3DSTE)-derived right atrial (RA) volumes and strains in healthy subjects. The study comprised 45 healthy adults, but 5 subjects were excluded due to inferior image quality for 3DSTE-derived RA assessments. The remaining 40 individuals being in sinus rhythm had a mean age of 35.1 ± 3.5 years (20 men). Two-dimensional, Doppler, 3DSTE and SCRTs were performed in all cases. RA maximum volume and total and passive RA stroke volumes correlated with the Valsalva ratio. Active RA stroke volume and emptying fraction showed correlations with 30/15 ratio. Peak global and mean segmental RA circumferential (CS) and longitudinal strains (LS) showed correlation with the Valsalva ratio. At atrial contraction, global RA-LS and mean segmental RA-CS showed correlations with the Valsalva ratio. Moreover, mean segmental RA-CS correlated with 30/15 ratio and mean segmental RA radial strain showed correlations with systolic blood pressure in response to standing. Autonomic neuropathy score correlated with peak global RA-LS. Autonomic function parameters have significant associations with specific RA functions in healthy adults, making the latter possible indicators of autonomic dysregulation.

Bladder dysfunction in adolescents with type 1 diabetes

It is increasingly significant that adults with diabetes experience lower urinary tract symptoms, however, there has been limited research in younger individuals with type 1 diabetes. To investigate bladder function using non-invasive urodynamics as a potential indicator of autonomic neuropathy in adolescents with type 1 diabetes. This involved examining the association between urinary flow disturbances, reported symptoms, and results from other autonomic tests. Cross-sectional study enrolling 49 adolescents with type 1 diabetes and 18 control subjects. All participants underwent uroflowmetry and ultrasound scanning, completed the Composite Autonomic Symptom Score (COMPASS)-31 questionnaire, and were instructed to record their morning urine volume and voiding frequencies and report them back. Cardiovascular reflex tests (CARTs) and the quantitative sudomotor axon reflex test (QSART) were performed. The main results are shown in the Summary figure. In this study, urological abnormalities were not significantly more frequent in adolescents with diabetes, however, urological issues were observed. This is supported by previous findings of Szabo etal. who found that adolescents with type 1 diabetes had reduced flow acceleration and time to maximum flow compared to control subjects. In our study, we observed cases with reduced acceleration and prolonged uroflow curves, possibly indicating detrusor underactivity. People with diabetes had a higher risk of nocturia than healthy controls, which our results supported. Some adolescents reported urination twice per night. Based on these findings, it is considered beneficial to ask about urological symptoms annually to determine if more examinations (frequency-volume charts and uroflowmetry) are necessary and/or if any opportunities for treatment optimization exist. However, uroflowmetry has limitations, as bladder filling and emptying is a complex process involving multiple pathways and neurological centers, making it difficult to standardize and evaluate. Another limitation of this study was that our control group was smaller and consisted of fewer males than females, which could affect the results due to differences in anatomy and physiology in the lower urinary tract system. In conclusion, adolescents with type 1 diabetes, as well as healthy adolescents, frequently experience urological symptoms. Although urological abnormalities were not significantly more frequent in adolescents with diabetes in this study, the focus on nocturia and risk for bladder dysfunction seems relevant, even in adolescents without any other tests indicating autonomic dysfunction.

The Importance of Evaluating Sudomotor Function in the Diagnosis of Cardiac Autonomic Neuropathy.

Cardiac autonomic neuropathy (CAN) is a disorder affecting the autonomic nerves that regulate the cardiovascular system, leading to irregular heart rate and blood pressure control. It is commonly associated with diabetes mellitus but can also result from other conditions such as autoimmune disorders, chronic kidney disease, alcohol abuse, and certain medications. Screening for CAN is essential, particularly in individuals with poor glycemic control, cardiovascular risk factors, or complications. Early identification of CAN is vital for timely intervention to prevent or manage cardiovascular complications effectively. Regular screening helps detect CAN before symptoms emerge, enabling early intervention to slow or halt its progression. This study examined the relationship between sudomotor function and cardiovascular reflex tests. This was a cross-sectional study conducted between June 2019 and June 2020. The study included 271 subjects aged 18 years and above who provided informed consent, were diagnosed with type 2 diabetes mellitus (T2DM), and were overweight or obese. Exclusion criteria encompassed patients with other types of diabetes, pregnant women, those with recent neoplasm diagnoses, stroke sequelae, history of myocardial infarction, or pelvic limb amputations. The assessment of cardiac autonomic neuropathy involved conducting an electrocardiogram and evaluating the QTc interval in the morning before taking medication. Additionally, cardiovascular reflex tests (CART) were conducted, including assessments of heart rate variability during deep breathing, the Valsalva maneuver, and changes in orthostatic position. Simultaneously, the diagnosis of CAN was assessed by performing a sweat test using a Sudoscan assessment (Impeto Medical, Moulineaux, France). Results: More than half of the participants (52%, n=143) were female. Significant differences in statistical measures were noted between females and males regarding age, systolic blood pressure, fasting blood glucose, A1c level, total cholesterol, triglycerides, gamma-glutamyl transferase, and bilirubin levels. Within the CAN-diagnosed group (CAN+), 40.92% were classified as mild cases (n=90), 47.27% as moderate cases (n=104), and 11.81% as severe cases (n=26). Among the CAN+ group, 54% (n=119) were women. Electrochemical skin conductance was lower in the CAN+ group than the CAN- group in hands (67.34±15.51 μS versus 72.38±12.12 μS, p=0.008) and feet (73.37±13.38 μS versus 82.84 ±10.29 μS, p<0.001). The Sudoscan-CAN score significantly correlated with Ewing scores (r= 0.522, p<0.001). In multiple linear regression analysis, the Sudoscan-CAN score remained significantly associated with age, high BMI, long-standing diabetes, and Ewing score. Sudoscan demonstrates potential in identifying patients with an increased risk of CAN. Its integration into clinical practice can improve patient outcomes through early detection, risk stratification, and personalized treatment approaches. Its non-invasive, portable, and user-friendly features render it suitable for utilization in outreach programs or resource-constrained settings as part of screening efforts designed to pinpoint high-risk individuals for additional assessment.

Mechanisms mediating muscle metaboreflex control of cardiac output during exercise: Impaired regulation in heart failure.

The ability to increase cardiac output during dynamic exercise is paramount for the ability to maintain workload performance. Reflex control of the cardiovascular system during exercise is complex and multifaceted involving multiple feedforward and feedback systems. One major reflex thought to mediate the autonomic adjustments to exercise is termed the muscle metaboreflex and is activated via afferent neurons within active skeletal muscle which respond to the accumulation of interstitial metabolites during exercise when blood flow and O2 delivery are insufficient to meet metabolic demands. This is one of the most powerful cardiovascular reflexes capable of eliciting profound increases in sympathetic nerve activity, arterial blood pressure, central blood volume mobilization, heart rate and cardiac output. This review summarizes the mechanisms meditating muscle metaboreflex-induced increases in cardiac output. Although much has been learned from studies using anaesthetized and/or decerebrate animals, we focus on studies in conscious animals and humans performing volitional exercise. We discuss the separate and interrelated roles of heart rate, ventricular contractility, ventricular preload and ventricular-vascular coupling as well as the interaction with other cardiovascular reflexes which modify muscle metaboreflex control of cardiac output. We discuss how these mechanisms may be altered in subjects with heart failure with reduced ejection fraction and offer suggestions for future studies.