Cardiovascular Autonomic Responses Research Articles

Cardiovascular Autonomic Dysfunction in Hospitalized Patients with a Bacterial Infection: A Longitudinal Observational Pilot Study in the UK.

A temporal reduction in the cardiovascular autonomic responses predisposes patients to cardiovascular instability after a viral infection and therefore increases the risk of associated complications. These findings have not been replicated in a bacterial infection. This pilot study will explore the prevalence of cardiovascular autonomic dysfunction (CAD) in hospitalized patients with a bacterial infection. A longitudinal observational pilot study was conducted. Fifty participants were included: 13 and 37 participants in the infection group and healthy group, respectively. Recruitment and data collection were carried out during a two-year period. Participants were followed up for 6 weeks: all participants' cardiovascular function was assessed at baseline (week 1) and reassessed subsequently at week 6 so that the progression of the autonomic function could be evaluated over that period of time. The collected data were thereafter analyzed using STATA/SE version 16.1 (StataCorp). The Fisher Exact test, McNemar exact test, Mann-Whitney test and Wilcoxon test were used for data analysis. 32.4% of the participants in the healthy group were males (n = 12) and 67.6% were females (n = 25). Participants' age ranged from 33 years old to 76 years old with the majority being 40-60 years of age (62.1%) (Mean age 52.4 SD = 11.4). Heart rate variability (HRV) in response to Valsalva Maneuver, metronome breathing, standing and sustained handgrip in the infection group was lower than in the healthy group throughout the weeks. Moreover, both the HRV in response to metronome breathing and standing up showed a statistically significant difference when the mean values were compared between both groups in week 1 (p = 0.03 and p = 0.013). The prevalence of CAD was significantly higher in the infection group compared to healthy volunteers, both at the beginning of the study (p = 0.018) and at the end of follow up (p = 0.057), when all patients had been discharged. CAD, as assessed by the HRV, is a common finding during the recovery period of a bacterial infection, even after 6 weeks post-hospital admission. This may increase the risk of complications and cardiovascular instability. It may therefore be of value to conduct a wider scale study to further evaluate this aspect so recommendations can be made for the cardiovascular autonomic assessment of patients while they are recovering from a bacterial infectious process.

Sympathetic Overactivity and Parasympathetic Impairment in Type 2 Diabetes: An Analysis of Cardiovascular Autonomic Functions.

Background Cardiovascular autonomic dysregulation is a known complication of Type 2 diabetes mellitus (T2DM), characterized by dysregulation in heart rate (HR) and blood pressure (BP). These disruptions in cardiovascular autonomic control can significantly influence the morbidity and mortality associated with the disease. Objectives This study aims to investigate how T2DM affects cardiovascular autonomic functions by comparing responses in HR, BP, and specific autonomic function tests between a control group without diabetes and a study group with diabetes. The research questions focus on assessing HR variability, baroreflex sensitivity, and other autonomic parameters to determine the extent of cardiovascular autonomic dysregulation in diabetic patients. Methods This cross-sectional study involved 200 adults, divided equally between a control group (n = 100) and a T2DM study group (n = 100). The exclusion criteria included cardiovascular diseases and renal impairment. Data collection involved assessing baseline characteristics such as age and BMI. Cardiovascular measures, including HR, systolic blood pressure (SBP), and diastolic blood pressure (DBP), were recorded after a five-minute rest. Autonomic function tests assessed sympathetic and parasympathetic responses, including the cold pressor test and the isometric hand grip exercise test. The statistical analysis was conducted using IBMSPSSStatistics for Windows, Version 25 (Released 2017; IBM Corp., Armonk, New York, United States), focusing on independent t-tests to compare between groups, considering p-values <0.05 as significant. Potential confounding variables like age and BMI were accounted for in the analysis to ensure robust findings Results The study group showed a higher average BMI (28.95 ± 5.60) compared to the control group (26.50 ± 5.70) and an increased resting HR (74.20 ± 8.60 bpm vs. 69.30 ± 9.10 bpm). The SBP was slightly higher in the study group (115.00 ± 19.00 mmHg vs. 114.50 ± 8.90 mmHg), while the DBP was lower (71.50 ± 10.70 mmHg vs. 72.80 ± 6.70 mmHg). The autonomic function tests showed a smaller increase in SBP (106.80 ± 11.00 mmHg) and a larger increase in DBP (75.90 ± 8.30 mmHg) upon standing in the study group compared to controls. The cold pressor test indicated increased sympathetic activity in the study group, with significant rises in SBP (133.70 ± 10.30 mmHg) and DBP (83.40 ± 9.00 mmHg) compared to the control group (SBP: 114.31 ± 11.87 mmHg, DBP: 71.85 ± 8.67 mmHg). These findings demonstrate marked differences in cardiovascular autonomic responses between the groups. Conclusions This study demonstrates that T2DM significantly impacts cardiovascular autonomic functions, with diabetic patients showing altered HR and BP indicative of increased sympathetic and decreased parasympathetic activity. These autonomic dysfunctions may heighten cardiovascular risk in diabetic individuals. Our findings highlight the importance of monitoring and managing cardiovascular autonomic functions in diabetic patients to reduce their risk of cardiovascular complications. Further research should investigate the underlying mechanisms and the effectiveness of interventions to improve autonomic function in this population.

Increases in cardiac vagal modulation following a single session of passive calf stretching

Autonomic cardiovascular responses to mechanoreflex activation by passive muscle stretching have been shown in numerous investigations. These cardiovascular adjustments include cardiac vagal inhibition, sympathetic activation, pressor response, and baroreflex resetting. However, it is currently unclear how the autonomic system responds after a single session of passive muscle stretching. Therefore, we aimed to test the hypothesis that there would be parasympathetic dominance after stretching cessation. Twenty-four volunteers (14 men; 22±3 yr) performed two protocols: 1) five sets of 1 minute of unilateral passive calf stretching with 15 s of rest; and 2) control condition (six minutes of resting at the same position). The autonomic cardiac responses of both control and experimental conditions were assessed before, and immediately, 15 minutes and 30 minutes after stretching cessation. Passive stretching was performed on an isokinetic dynamometer (Biodex System 4, USA). Heart rate, systolic and diastolic blood pressure were continuously measured on a beat-to-beat basis using lead II electrocardiography (BioAmp, MLA2540) and finger photoplethysmography (Human NIBP, Australia). Brachial arterial blood pressure was also measured with an automated digital sphygmomanometer (Dixtal, DX2022, Brazil). Heart rate variability (HRV) was determined following the guidelines of the Task Force of the European Society of Cardiology and the North American Society of Pacing. With regards to the hemodynamics variables, there was no significant difference in the heart rate before and after passive stretching, while mean blood pressure (MBP) was slightly higher (±2mmHg) 30 min following both protocols (control, p=0.027 and stretch, p=0.035). Regarding HRV analysis, in the time domain, RMSSD was significantly increased 30 min following passive stretching (+15%; p=0.029), and this effect was also detected when using the frequency domain (high frequency: +37%, p=0.039). Of note, our major findings were not affected by sex. In conclusion, autonomic cardiovascular control shifts to a parasympathetic dominant state following passive calf stretch, and the effect peaks around 30 minutes after stretching. Passive stretching seems to be a safe, easy, and effective form of exercise that evokes autonomic cardiovascular responses during and following its cessation, even if it is performed in a single session of stretch. CNPq 307764/2022-2; CAPES (001) QUT South America Scholarship. 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.

Sex Differences in Sympathetic Responses to Lower-Body Negative Pressure.

Trauma-induced hemorrhage is a leading cause of death in prehospital settings. Experimental data demonstrate that females have a lower tolerance to simulated hemorrhage (i.e., central hypovolemia). However, the mechanism(s) underpinning these responses are unknown. Therefore, this study aimed to compare autonomic cardiovascular responses during central hypovolemia between the sexes. We hypothesized that females would have a lower tolerance and smaller increase in muscle sympathetic nerve activity (MSNA) to simulated hemorrhage. Data from 17 females and 19 males, aged 19-45 yr, were retrospectively analyzed. Participants completed a progressive lower-body negative pressure (LBNP) protocol to presyncope to simulate hemorrhagic tolerance with continuous measures of MSNA and beat-to-beat hemodynamic variables. We compared responses at baseline, at two LBNP stages (-40 and -50 mmHg), and at immediately before presyncope. In addition, we compared responses at relative percentages (33%, 66%, and 100%) of hemorrhagic tolerance, calculated via the cumulative stress index (i.e., the sum of the product of time and pressure at each LBNP stage). Females had lower tolerance to central hypovolemia (female: 561 ± 309 vs male: 894 ± 304 min·mmHg [time·LBNP]; P = 0.003). At LBNP -40 and -50 mmHg, females had lower diastolic blood pressures (main effect of sex: P = 0.010). For the relative LBNP analysis, females exhibited lower MSNA burst frequency (main effect of sex: P = 0.016) accompanied by a lower total vascular conductance (sex: P = 0.028; main effect of sex). Females have a lower tolerance to central hypovolemia, which was accompanied by lower diastolic blood pressure at -40 and -50 mmHg LBNP. Notably, females had attenuated MSNA responses when assessed as relative LBNP tolerance time.

Maternal Cardiovascular Responses to Position Change in Pregnancy.

The maternal cardiovascular-circulatory system undergoes profound changes almost from the conception of a pregnancy until the postpartum period to support the maternal adaptions required for pregnancy and lactation. Maintenance of cardiovascular homeostasis requires changes in the cardiovascular autonomic responses. Here, we present a longitudinal study of the maternal cardiovascular autonomic responses to pregnancy and maternal position. Over a normal gestation, in the left lateral position there are significant changes in both time and frequency domain parameters reflecting heart rate variability. We show that cardiovascular autonomic responses to physiological stressors (standing and supine positions in late pregnancy) became significantly different with advancing gestation. In the third trimester, 60% of the subjects had an unstable heart rate response on standing, and these subjects had a significantly reduced sample entropy evident in their heart rate variability data. By 6 weeks, postpartum function returned to near the non-pregnant state, but there were consistent differences in high-frequency power when compared to nulligravid cases. Finally, we review complementary evidence, in particular from magnetic resonance imaging, that provides insights into the maternal and fetal impacts of positioning in pregnancy. This demonstrates a clear relationship between supine position and maternal hemodynamic parameters, which relates to compression of the inferior vena cava (p = 0.05). Together, these studies demonstrate new understanding of the physiology of physiological stressors related to position.

Hemodynamic responses to low-level transcutaneous auricular nerve stimulation in young volunteers.

The aim of this study was to characterize cardiovascular autonomic responses during two constant current intensities below sensory threshold of transcutaneous auricular nerve stimulation (taNS). On this basis, a protocol for taNS with autonomic modulatory potential could be proposed. We included 26 men and 24 women, mean age 26. Data were collected during three randomly allocated 20-minute right tragus stimulation sessions - a) no-stimulation (sham), b) 90µA (arbitrary), and c) 130µA (near the lowest sensory threshold in majority). Stimulation was 20Hz, rectangular pulse width of 2ms, duty cycle 2-second on/off. To assess autonomic responses, we continuously recorded ECG, non-invasive arterial blood pressure (BP) and thoracic impedance cardiography data. Ten-minute data were compared. Fast Fourier transform of RR intervals was performed on 10-minute recordings as well. Low frequency and high frequency power spectra were calculated. Friedman test or one-way ANOVA for repeated measurements and Mann-Whitney or Wilcoxon's signed-rank test, or t-test were carried out. P<0.05 was considered significant. At 130µA stimulation, cardiac output significantly decreased (p<0.05), driven by significant heart rate drop in women, and stroke volume and contractility drop in men, pointing to a gender-related autonomic responses. We observed no significant changes in BP, or variability parameters. Significantly higher body size and BP were found in men, as expected. It seems that tested taNS protocol has a potential for cardiac autonomic modulation in majority of young healthy men as well as women. Further studies are however needed to prove the therapeutic potential of this stimulation protocol in different patient groups.

Both whole-body rotation and visual flow induce cardiovascular autonomic response in human, but visual response is overridden by vestibular stimulation

While the influence of the vestibular and extra-vestibular gravity signals on the cardiovascular system has been demonstrated, there is little evidence that visual stimuli can trigger cardiovascular responses. Furthermore, there is no evidence of interaction between visual and vestibular signals in autonomic control, as would be expected since they are highly integrated. The present study explored the cardiovascular responses to vestibular and visual stimuli in normal subjects. We hypothesized that the visual stimuli would modify the cardiovascular response to vestibular stimulation, especially when the latter is ambiguous with respect to gravity. Off-Vertical-Axis-Rotation (OVAR) was used to stimulate vestibular and extra-vestibular receptors of gravity in 36 healthy young adults while virtual reality was used for visual stimulation. Arterial pressure (AP), respiratory rate and ECG were measured. The analysis accounted for the respiratory modulation of AP and heart rate (HR). Vestibular stimulation by OVAR was shown to modulate both mean arterial pressure (MAP) and HR, while the visual stimulation was significantly affecting HR modulation, but not MAP. Moreover, the specific visual effect was present only when the subjects were not in rotation. Therefore, visual stimulation is able to modulate the heart rate, but is overridden by vestibular stimulation due to real movement.

Past strong experiences determine acute cardiovascular autonomic responses to acoustic stress

Stress is a major risk factor for cardiovascular (CV) disease. We hypothesized that past strong experiences might modulate acute CV autonomic responses to an unexpected acoustic stimulus. A i m: The study's aim was to compare acute CV autonomic responses to acoustic stress between students with and without a past strong experience associated with the acoustic stimulus. Twenty five healthy young volunteers - medical and non-medical students - were included in the study. CV hemodynamic parameters, heart rate (HR), and blood pressure (BP) variability were assessed for 10 min at rest and for 10 min after two different acoustic stimuli: a standard sound signal and a specific sound signal used during a practical anatomy exam (so-called "pins"). Both sounds stimulated the autonomic nervous system. The "pins" signal caused a stronger increase in HR in medical students (69 ± 10 vs. 73 ± 13 bpm, p = 0.004) when compared to non-medical students (69 ± 6 vs. 70 ± 10, p = 0.695). Rises in diastolic BP, observed 15 seconds after sound stressors, were more pronounced after the "pins" sound than after the standard sound signal only in medical students (3.1% and 1.4% vs. 3% and 4.4%), which was also reflected by low-frequency diastolic BP variability (medical students: 6.2 ± 1.6 vs. 4.1 ± 0.8 ms2, p = 0.04; non-medical students: 6.0 ± 4.3 vs. 4.1 ± 2.6 ms2, p = 0.06). The "pins" sound, which medical students remembered from their anatomy practical exam, provoked greater sympathetic activity in the medical student group than in their non-medical peers. Thus, past strong experiences modulate CV autonomic responses to acute acoustic stress.

Cardiovascular autonomic responses in reproductive and post-menopausal women

Background: Autonomic responses are a sensitive indicator for assessing balance in sympatho-vagal system. Many studies have shown an increased response in the sympathetic system in post-menopausal women. Alteration in autonomic nerve function causes an increased incidence of hypertension, arrhythmias, or acute coronary syndrome. Thus, this study aims to find out the heart rate variability (HRV) among reproductive and post-menopausal women. Aims and Objectives: The aim of the study was to compare the cardiovascular autonomic responses among reproductive and post-menopausal women. Materials and Methods: This cross-sectional study was conducted in the department of physiology at government medical college, Kottayam on 40 reproductive and 40 post-menopausal women. Using PHYSIOPAC-PP4 (Medicaid Systems Chandigarh) machine, an electrocardiogram was recorded in both groups in the supine position for 5 min. The frequency and time domain data obtained were analyzed using SPSS software. Results: The mean age group in reproductive women was 43 and post-menopausal women was 54. In the power spectrum analysis of HRV parameters the mean value of frequency domain Low frequency (LF) in reproductive women was 72.05 (S.D = 5.706) and post-menopausal women was 79.48 (S.D = 3.789). The high frequency (HF) in reproductive women was 28 (S.D = 5.588) and post-menopausal women were 20.53 (S.D = 3.789). The LF/HF ratio mean value obtained in reproductive women was 2.723 (S. D = 0.759) and post–menopausal was 3.992 (S.D 0.785). In the various time domain parameters, we estimated the mean value of the root mean square of successive differences (RMSSD) between normal heartbeats RMSSD and obtained the value in reproductive women as 25.05 (S.D = 11.88) and post-menopausal women as 12.68 (S.D = 5.535). The RR interval triangular index mean value in reproductive women was 0.0520 (S.D = 0.013) and post-menopausal women were 0.0345 (S.D = 0.01). In all these parameters, the P-value was found to be &lt;0.001, so statistically highly significant. Conclusion: In this study, higher values in time domain and frequency domain parameters for assessing sympathetic functions were seen in postmenopausal women when compared to women of the reproductive age group which was statistically significant. This may be due to age and hormonal influences. The power spectrum analysis of HRV parameters was proved to be a noninvasive method to assess the sympathovagal balance in the study group of women.

Physically active men present a healthier cardiometabolic profile in response to a balanced meal compared to inactive men.

Post-meal cardiometabolic responses are critical for health, and may be influenced by physical activity. The objective of this study was to investigate the effect of habitual physical activity level on the metabolic, autonomic nervous system and cardiovascular responses to a balanced meal in healthy men. 12 active and 12 inactive healthy males, matched for age and body composition, attended the laboratory in fasting condition. Participants were asked to sit quietly and comfortably in an armchair for the whole duration of the experiment (~ 2h30). Metabolic, autonomic nervous system and cardiovascular measurements were performed in fasting conditions, and at regular intervals until one hour after the end of a balanced breakfast. No significant difference was observed between groups in glycaemia or energy expenditure throughout the experiment. Fat oxidation rate was significantly higher one-hour post-meal in active vs inactive men (Respiratory Quotient: 0.78 ± 0.04 vs 0.88 ± 0.03; p < 0.01). Heart rate was significantly lower in active compared to inactive individuals (p < 0.001) throughout the experiment and active participants displayed significantly enhanced vagal tone one-hour post-meal (square root of the sum of successive differences between adjacent normal R-R intervals squared: 72.4 ± 27.9 vs 46.4 ± 14.1ms; p < 0.05). In healthy men, habitual physical activity level seems discriminant to decipher specific profiles in terms of cardiometabolic responses to a meal. Overall, it may suggest pre-signal cardiometabolic impairments in healthy inactive individuals and highlight the need to consider primary prevention in inactive subjects as a key factor for health management.

Gravitational Dose-Response Curves for Acute Cardiovascular Hemodynamics and Autonomic Responses in a Tilt Paradigm.

Background The cardiovascular system is strongly dependent on the gravitational environment. Gravitational changes cause mechanical fluid shifts and, in turn, autonomic effectors influence systemic circulation and cardiac control. We implemented a tilt paradigm to (1) investigate the acute hemodynamic response across a range of directions of the gravitational vector, and (2) to generate specific dose-response relationships of this gravitational dependency. Methods and Results Twelve male subjects were tilted from 45° head-up tilt to 45° head-down tilt in 15° increments, in both supine and prone postures. We measured the steady-state hemodynamic response in a range of variables including heart rate, stroke volume, cardiac output, oxygen consumption, total peripheral resistance, blood pressure, and autonomic indices derived from heart rate variability analysis. There is a strong gravitational dependence in almost all variables considered, with the exception of oxygen consumption, whereas systolic blood pressure remained controlled to within ≈3% across the tilt range. Hemodynamic responses are primarily driven by differential loading on the baroreflex receptors, combined with differences in venous return to the heart. Thorax compression in the prone position leads to reduced venous return and increased sympathetic nervous activity, raising heart rate, and systemic vascular resistance while lowering cardiac output and stroke volume. Conclusions Gravitational dose-response curves generated from these data provide a comprehensive baseline from which to assess the efficacy of potential spaceflight countermeasures. Results also assist clinical management of terrestrial surgery in prone posture or head-down tilt positions.

Low-dose morphine reduces pain perception and blood pressure, but not muscle sympathetic outflow, responses during the cold pressor test.

Our knowledge about how low-dose (analgesic) morphine affects autonomic cardiovascular regulation is primarily limited to animal experiments. Notably, it is unknown if low-dose morphine affects human autonomic cardiovascular responses during painful stimuli in conscious humans. Therefore, we tested the hypothesis that low-dose morphine reduces perceived pain and subsequent sympathetic and cardiovascular responses in humans during an experimental noxious stimulus. Twenty-nine participants (14 females/15 males; 29 ± 6 yr; 26 ± 4 kg·m-2, means ± SD) completed this randomized, crossover, placebo-controlled trial during two laboratory visits. During each visit, participants completed a cold pressor test (CPT; hand in ∼0.4°C ice bath for 2 min) before and ∼35 min after drug/placebo administration (5 mg iv morphine or saline). We compared pain perception (100 mm visual analog scale), muscle sympathetic nerve activity (MSNA; microneurography; 14 paired recordings), and beat-to-beat blood pressure (BP; photoplethysmography) between trials (at both pre- and postdrug/placebo time points) using paired, two-tailed t tests. Before drug/placebo infusion, perceived pain (P = 0.92), ΔMSNA burst frequency (n = 14, P = 0.21), and Δmean BP (P = 0.39) during the CPT were not different between trials. After the drug/placebo infusion, morphine versus placebo attenuated perceived pain (morphine: 43 ± 20 vs. placebo: 57 ± 24 mm, P < 0.001) and Δmean BP (morphine: 10 ± 7 vs. placebo: 13 ± 8 mmHg, P = 0.003), but not ΔMSNA burst frequency (morphine: 10 ± 11 vs. placebo: 13 ± 11 bursts·min-1, P = 0.12), during the CPT. Reductions in pain perception and Δmean BP were only weakly related (r = 0.34, P = 0.07; postmorphine CPT minus postplacebo CPT). These data provide valuable information regarding how low-dose morphine affects autonomic cardiovascular responses during an experimental painful stimulus.NEW & NOTEWORTHY In this randomized, crossover, placebo-controlled trial, we found that low-dose morphine administration reduced pain perception and blood pressure responses during the cold pressor test via attenuated increases in heart rate and cardiac output. We also determined that muscle sympathetic outflow responses during the cold pressor test seem to be unaffected by low-dose morphine administration. Finally, our exploratory analysis suggests that biological sex does not influence morphine-induced antinociception in healthy adults.

Conditional Regulation of Blood Pressure in Response to Emotional Stimuli by the Central Nucleus of the Amygdala in Rats.

Humans and animals can determine whether a situation is favorable to them and act accordingly. For this, the autonomic tuning of the cardiovascular system to supply energy to active skeletal muscles through the circulatory system is as important as motor control. However, how the autonomic cardiovascular responses are regulated in dynamically changing environments and the neuronal mechanisms underlying these responses remain unclear. To resolve these issues, we recorded the blood pressure and heart rate of head-restrained rats during dynamically changing appetitive and aversive classical conditioning tasks. The rats displayed various associations between conditioned stimuli and unconditioned stimuli in appetitive (sucrose water), neutral (no outcome), and aversive (air puff) blocks. The blood pressure and heart rate in the appetitive block gradually increased in response to the reward-predicting cue and the response to the actual reward vigorously increased. The reward-predictive response was significantly higher than the responses obtained in the neutral and aversive condition blocks. To investigate whether the reward-predictive pressor response was caused by orofacial movements such as anticipatory licking behavior, we separately analyzed high- and low-licking trials. The conditioned pressor response was observed even in trials with low-licking behaviors. Blood pressure and heart rate responses to the air puff-predicting cue in the aversive block were not significantly different from the responses in the neutral block. The conditioned blood pressure response rapidly changed with condition block switching. Furthermore, to examine the contribution of the amygdala as an emotion center to these conditioned responses, we bilaterally microinjected a GABAA receptor agonist, muscimol, into the central nucleus of the amygdala. Pharmacological inactivation of the central nucleus of the amygdala significantly decreased the reward-predictive pressor responses. These results suggest that the blood pressure is adaptively and rapidly regulated by emotional conditioned stimuli and that the central nucleus of the amygdala participates in regulating the pressor response in dynamically changing situations.

Lower blood pressure, but not muscle sympathetic nerve activity, in female compared to male adults during progressive central hypovolemia

INTRODUCTIONRapid adjustments in cardiac output and sympathetically‐mediated vasoconstriction are critical to prevent blood pressure (BP) from falling during central hypovolemia. Female adults have a reduced ability to tolerate central hypovolemia (i.e., orthostatic hypotension), potentially due to reduced sympathetically‐mediated vasoconstriction. However, there are minimal data evaluating sex differences in muscle sympathetic nerve activity (MSNA) during pre‐syncopal limited central hypovolemia. Therefore, the purpose of this study was to compare autonomic cardiovascular responses during central hypovolemia between sexes. We tested the hypothesis that young healthy female, compared to male, adults would have a lower tolerance to progressive hypovolemia, accompanied by attenuated MSNA responses.METHODSTwenty‐eight female (28±8 years old, 170±7 cm, 75±8 kg, BMI: 26±3 kg/m2) and 31 male (age: 30±5 years old, height: 176±6 cm, mass: 82±9 kg, BMI: 26±3 kg/m2) adults completed a staged lower‐body negative pressure (LBNP) protocol. The LBNP protocol started at minus 40 mmHg (LBNP40) and was further reduced by 10 mmHg every 3 minutes until the participant reached pre‐syncope. MSNA (radial nerve), heart rate, and BP were collected continuously throughout the protocol. LBNP tolerance was quantified as a cumulative stress index (mmHg*min) and was compared between sexes using a two‐tailed Mann‐Whitney test. MSNA, heart rate, and BP responses during LBNP were compared between sexes (LBNP stage [repeated measure] x sex) using mixed‐model analysis of variance tests.RESULTSConsistent with prior findings, female adults had a lower tolerance to progressive LBNP (female: 513±283 vs. male: 929±357 mmHg*min, p&lt;0.0001). Due to more females reaching pre‐syncope sooner in the protocol, we compared responses during the early stages of LBNP. At these early LBNP stages (LBNP40 &amp; LBNP50), significant interactions for heart rate and BP were observed (heart rate: p&lt;0.0001, BP: p=0.0464). Post‐hoc analyses revealed a significantly higher heart rate (98±20 vs. 82±15 bpm, p&lt;0.0001) and lower mean BP (80±11 vs. 87±7 mmHg, p = 0.0343) in females at LBNP50. However, MSNA burst frequency responses were not different between sexes at the assessed time points (female vs. male; Baseline: 14±9 vs. 17±10, LBNP40: 29±14 vs. 34±12, LBNP50: 34±16 vs. 35±16 bursts/min; sex: p=0.2685, interaction: p=0.2334, stage: p&lt;0.0001).DISCUSSIONConsistent with previous reports, this study demonstrated a lower tolerance to progressive central hypovolemia in female compared to male adults. However, contrary to our hypothesis, there was no difference in MSNA burst frequency between sexes, despite lower BP in female adults during the early stages of LBNP. These findings support the need for future studies to explore other mechanisms contributing to sex differences in tolerance to central hypovolemia.

Blunted short-term autonomic cardiovascular reactivity to orthostatic and clinostatic challenges in fibromyalgia as an indicator of the severity of chronic pain

Fibromyalgia is a long-term pain disorder that has been related to autonomic dysfunctions and reduced cardiovascular reactivity. We aimed to assess the dynamic short-term cardiovascular responses to postural changes in fibromyalgia. Thirty-eight women with fibromyalgia and thirty-six healthy women underwent the “Chronic Pain Autonomic Stress Test”. Electrocardiogram, blood pressure and impedance cardiography were continuously recorded during active standing and lying down. Second-by-second values were derived over the first 30 s of each posture. Lower reactivity during the beginning of each position was observed in fibromyalgia sufferers compared to healthy women, with smaller responses seen during stand up in heart rate, blood pressure, cardiac output, total peripheral resistance, and pre-ejection period, and smaller changes during lying down in heart rate, cardiac output and total peripheral resistance. The magnitude of the autonomic adjustments to postural changes was inversely associated with the severity of clinical pain. These findings indicate an early impaired autonomic cardiovascular response to orthostatic and clinostatic challenges in fibromyalgia, suggesting less autonomic flexibility and adaptability to situational demands and challenges. Short-term second-by-second cardiovascular measures may be useful in the clinical assessment of fibromyalgia.

Stress and the baroreflex.

The stress response to emotions elicits the release of glucocorticoids from the adrenal cortex, epinephrine from the adrenal medulla, and norepinephrine from the sympathetic nerves. The baroreflex adapts to buffer these responses to ensure that perfusion to the organs meets the demands while maintaining blood pressure within a within a narrow range. While stressor-evoked autonomic cardiovascular responses may be adaptive for the short-term, the recurrent exaggerated cardiovascular stress reactions can be maladaptive in the long-term. Prolonged stress or loss of the baroreflex's buffering capacity can predispose episodes of heightened sympathetic activity during stress leading to hypertension, tachycardia, and ventricular wall motion abnormalities. This review discusses 1) how the baroreflex responds to acute and chronic stressors, 2) how lesions in the neuronal pathways of the baroreflex alter the ability to respond or counteract the stress response, and 3) the techniques to assess baroreflex sensitivity and stress responses. Evidence suggests that loss of baroreflex sensitivity may predispose heightened autonomic responses to stress and at least in part explain the association between stress, mortality and cardiovascular diseases.

Turner-Kieser Syndrome or Iliac Horn Syndrome, a Challenge for the Anesthesiologist: A Case Report and a Literature Review

Turner-Kieser syndrome is a rare genetic disorder, autosomal dominant, which is related to variable gene expression and high penetrance, due to mutations in the LMX1B gene that affects connective tissue. The clinic has characteristics with alterations in nails, knees, elbows, and presence of iliac horns that makes the anesthetic difficult. However, data in the literature needs more research on this area. The present report is a cesarean section under general intravenous anesthesia performed on a 32-week pregnant woman due to the maternal risk of full-term evolution and aims to contribute to the anesthetic management of patients with this syndrome as there are few descriptions in the literature regarding the anesthetic management in Turner-Kieser syndrome. Even being a case report, the syndrome is rare and it is important to be reported to all anesthesiologists becoming aware of its management and to choose the best technique and anticipate possible complications. During general anesthesia, the technique chosen for the case reported here, we emphasize the risks of possible difficulty in intubating and positioning the patient, as well as renal impairment caused by changes in the cardiovascular autonomic response due to the choice of some drugs. Therefore, in the present report, our option was intravenous general anesthesia because of maternal complications, where fast acting drugs without renal metabolism or excretion were selected, resulting in an uneventful anesthetic procedure.

Rasagiline does not exacerbate autonomic blood pressure dysregulation in early or mild Parkinson’s disease

IntroductionOrthostatic hypotension (OH) and abnormal blood pressure (BP) fluctuations occur mainly due to noradrenergic dysfunction and are clinically important in patients with Parkinson’s disease (PD). They lead to impairments of cognition function, daily activities, and quality of life. Some monoamine oxidase (MAO)-B inhibitors have a sympathomimetic amine, which can be attributed to OH. Therefore, we determined whether rasagiline, a common MAO-B inhibitor used in PD treatment, can contribute to cardiovascular autonomic BP dysregulation in patients with early or mild PD. MethodsNineteen patients with early or mild PD were recruited, and tilt test and 24-h ambulatory BP monitoring (ABPM) were performed before and after rasagiline administration. Early or mild PD was defined as patients with de novo (n = 4), levodopa (n = 10), dopamine agonist (n = 1), levodopa and one dopamine agonist (n = 2), levodopa and droxidopa (n = 1), and levodopa and istradefylline (n = 1). Furthermore, patients with motor fluctuation and multiple dopamine agonists were excluded from our study. ResultsOH and BP frequency were not significantly exacerbated before or after rasagiline administration. No significant differences of type in BP fluctuation on ABPM and the degree of nocturnal BP falls were found before and after rasagiline administration. The Unified Parkinson’s Disease Rating Scale motor score in patients (post-rasagiline administration) was significantly improved compared with before. ConclusionRasagiline seems to be a suitable medication for Parkinsonian symptoms in patients with early and mild PD. It does not exacerbate cardiovascular autonomic responses, circadian rhythm of BP, or both.

Low-dose fentanyl reduces pain perception, muscle sympathetic nerve activity responses, and blood pressure responses during the cold pressor test.

Our knowledge about how low-dose (analgesic) fentanyl affects autonomic cardiovascular regulation is primarily limited to animal experiments. Notably, it is unknown if low-dose fentanyl influences human autonomic cardiovascular responses during painful stimuli in humans. Therefore, we tested the hypothesis that low-dose fentanyl reduces perceived pain and subsequent sympathetic and cardiovascular responses in humans during an experimental noxious stimulus. Twenty-three adults (10 females/13 males; 27 ± 7 yr; 26 ± 3 kg·m-2, means ± SD) completed this randomized, crossover, placebo-controlled trial during two laboratory visits. During each visit, participants completed a cold pressor test (CPT; hand in ∼0.4°C ice bath for 2 min) before and 5 min after drug/placebo administration (75 μg fentanyl or saline). We compared pain perception (100-mm visual analog scale), muscle sympathetic nerve activity (MSNA; microneurography, 11 paired recordings), and beat-to-beat blood pressure (BP; photoplethysmography) between trials (at both pre- and postdrug/placebo timepoints) using paired, two-tailed t tests. Before drug/placebo administration, perceived pain (P = 0.8287), ΔMSNA burst frequency (P = 0.7587), and Δmean BP (P = 0.8649) during the CPT were not different between trials. After the drug/placebo administration, fentanyl attenuated perceived pain (36 vs. 66 mm, P < 0.0001), ΔMSNA burst frequency (9 vs. 17 bursts/min, P = 0.0054), and Δmean BP (7 vs. 13 mmHg, P = 0.0174) during the CPT compared with placebo. Fentanyl-induced reductions in pain perception and Δmean BP were moderately related (r = 0.40, P = 0.0641). These data provide valuable information regarding how low-dose fentanyl reduces autonomic cardiovascular responses during an experimental painful stimulus.

Cardiovascular autonomic responses during head-up tilt test in newly diagnosed type 2 diabetes.

Autonomic dysfunction is commonly observed in patients with long-standing type 2 diabetes. Previous studies have confirmed the value of both subjectively assessed symptoms and objective measurements of autonomic nervous system function in diagnosing cardiovascular autonomic neuropathy. However, the head-up tilt test (HUTT) has been rarely used to investigate cardiovascular autonomic responses in subjects with high risk ofnewly diagnosed type 2 diabetes (nT2D). To evaluate autonomic cardiovascular responses through passive orthostatic challenge along the diabetes continuum. The study population was stratified as normoglycemic (n = 16), prediabetes (n = 20), and nT2D (n = 20). The prevalence of orthostatic intolerance and autonomic cardiovascular responses was evaluated with the Task Force Monitor during a 30-min passive HUTT. Spectral indices of heart rate and blood pressure variability and baroreceptor effectiveness index (BEI) were calculated through the HUTT. BEI was obtained by the sequence method. There were no differences in the prevalence of orthostatic intolerance or in the indices of heart rate and blood pressure variability among the three groups of study. The BEI was attenuated in the nT2D group in supine rest and throughout HUTT compared with normoglycemic and prediabetes groups. The multivariable linear regression analysis showed that BEI was associated with fasting glucose (β = - 0.52, p <0.001) and HbA1c (β = - 0.57, p <0.001) independently of cardiovascular risk factors. Cardiovascular autonomic neuropathy, expressed as blunted BEI, is the only abnormal autonomic nervous test detected in nT2D, and it was independently associated with fasting glucose and HbA1c values.