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Background: The harsh environmental conditions during space travel, particularly weightlessness, impose a major burden on the human body including the cardiovascular system. Given its importance in adjusting the cardiovascular system to environmental challenges, the autonomic nervous system has been in the focus of scientists and clinicians involved in human space flight. This review provides an overview on human autonomic research under real and simulated space conditions with a focus on orthostatic intolerance.Methods: The authors conducted a targeted literature search using Pubmed.Results: Overall, 120 articles were identified and included in the review.Conclusions: Postflight orthostatic intolerance is commonly observed in astronauts and could pose major risks when landing on another celestial body. The phenomenon likely results from changes in volume status and adaptation of the autonomic nervous system to weightlessness. Over the years, various non-pharmacological and pharmacological countermeasures have been investigated. In addition to enabling safe human space flight, this research may have implications for patients with disorders affecting cardiovascular autonomic control on Earth. [ABSTRACT FROM AUTHOR]

Background : We investigated whether the results of autonomic function tests correlate with body composition and shape in healthy young people. Methods : We conducted cardiovascular reflex tests (heart rate [HR] and blood pressure [BP] responses to the Valsalva maneuver and HR response to deep breathing) and the tilt table test with 32 subjects (19 males; mean age, 22.1±1.9 years). Participants also completed an anthropometric measurement sequence (weight; height; upper arm, hips, and waist circumference; triceps and subscapular skinfold), bioelectric impedance testing, and hand grip strength measurements. Results : Markers of obesity, other anthropometric measures, functional measures, and the basal metabolic rate (BMR) were significantly positively correlated with systolic BP (SBP) and diastolic BP (DBP) in both the supine and tilted positions. There was a positive correlation between the difference in HR (ΔHR) between the tilt and supine body positions and markers of obesity, the functional marker of dominant handgrip strength, and BMR. Participants with a body mass index (BMI)

Purpose: To evaluate cardiovascular and sudomotor function during wakefulness and to assess autonomic symptoms in de novo patients with type 1 narcolepsy compared to healthy controls. Methods: De novo patients with type 1 narcolepsy (NT1) and healthy controls underwent cardiovascular function tests including head-up tilt test, Valsalva maneuver, deep breathing, hand grip, and cold face, and sudomotor function was assessed through Sudoscan. Autonomic symptoms were investigated using the Scales for Outcomes in Parkinson's Disease–Autonomic Dysfunction (SCOPA-AUT) questionnaire. Results: Twelve de novo patients with NT1 and 14 healthy controls were included. In supine rest condition and at 3 min and 10 min head-up tilt test, the systolic blood pressure values were significantly higher in the NT1 group than in controls (p < 0.05). A lower Valsalva ratio (p < 0.01), significantly smaller inspiratory–expiratory difference in deep breathing (p < 0.05), and lower delta heart rate in the cold face test (p < 0.01) were also observed in the NT1 group. The mean hand electrochemical skin conductance values were significantly lower (p < 0.05) and the mean SCOPA-AUT total scores were significantly higher in patients with NT1 than in healthy subjects (p < 0.001), with greater involvement of cardiovascular and thermoregulatory items. Conclusion: De novo patients with NT1 exhibit blunted parasympathetic activity during wakefulness, mild sudomotor dysfunction, and a large variety of autonomic symptoms. [ABSTRACT FROM AUTHOR]

Background: We investigated whether the results of autonomic function tests correlate with body composition and shape in healthy young people. Methods: We conducted cardiovascular reflex tests (heart rate [HR] and blood pressure [BP] responses to the Valsalva maneuver and HR response to deep breathing) and the tilt table test with 32 subjects (19 males; mean age, 22.1±1.9 years). Participants also completed an anthropometric measurement sequence (weight; height; upper arm, hips, and waist circumference; triceps and subscapular skinfold), bioelectric impedance testing, and hand grip strength measurements. Results: Markers of obesity, other anthropometric measures, functional measures, and the basal metabolic rate (BMR) were significantly positively correlated with systolic BP (SBP) and diastolic BP (DBP) in both the supine and tilted positions. There was a positive correlation between the difference in HR (HR) between the tilt and supine body positions and markers of obesity, the functional marker of dominant handgrip strength, and BMR. Participants with a body mass index (BMI) <25 kg/m² had significantly lower median values of HR, DBP in the tilttest, SBP at rest, and SBP in the tilt-test than participants who had a BMI =25 kg/m² (10.55 vs. 21.95 bpm, P=0.003; 77.55 vs. 90.05 mmHg, P=0.045; 113.45 vs. 140.55 mmHg, P=0.013; 117.00 vs. 135.25 mmHg, P=0.006, respectively). Body fat percentage was identified as an independent positive predictor (β=0.993; 95% confidence interval [CI], 0.070 to 1.916; P=0.036) and body water percentage was an independent negative predictor of tilted SBP (β=-1.370; 95% CI, -2.634 to 0.106; P=0.035). Conclusion: High sympathetic activity, as evaluated by cardiovascular regulation, correlates with a high share of adipose tissue in young healthy persons. [ABSTRACT FROM AUTHOR]

The aim of this study was to test the hypothesis that plasma sphingosine 1-phosphate (S1P) levels are associated with the risk of cardiovascular autonomic neuropathy (CAN) in type 2 diabetes patients. This cross-sectional study included 287 individuals with type 2 diabetes. CAN was evaluated using cardiovascular reflex tests. Logistic regression analyses were conducted to assess the relationship between plasma S1P levels and CAN. Plasma S1P concentrations were significantly lower in individuals with CAN than in those without CAN. There was a significant interaction between plasma S1P levels and sex with respect to CAN (p for interaction = 0.003). When stratified by sex, the association between plasma S1P levels and CAN exhibited a sex difference; in multivariable analysis, plasma S1P levels were significantly associated with CAN in women (odds ratio per standard deviation increase in the log-transformed value, 0.40; 95% confidence interval, 0.23–0.70, p = 0.001). However, there was no significant association between plasma S1P and CAN in men. Plasma S1P concentrations were inversely associated with CAN only in women with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Little is known about the physiological response to the cold pressor test (CPT) when in a clinically-induced state of autonomic nervous system (ANS) imbalance, despite its utility in various disease- and injury-states. To date, research in this area is limited to acute aerobic and isometric exercise, with a paucity of research investigating the effects of anaerobic exercise on the physiological response to the CPT. Therefore, the purpose of our study was to assess the effects of the Wingate anaerobic cycle test (WAT) on cardiovascular (CV) and metabolic recovery following the CPT in a group of healthy adult males. A pre-post intervention study was conducted, whereby 10 healthy adult males (age = 29 ± 4 years, height = 182 ± 7 cm, mass = 83 ± 9 kg) completed a baseline cold pressor test (CPT-only) and a follow-up cold pressor test preceded by a Wingate anaerobic exercise test (WAT+CPT). Recovery slopes for various CV and metabolic variables, including heart rate (HR), blood pressure (BP), and relative oxygen consumption (V̇O2) were analyzed using single-subject analysis, with celeration line slopes calculated for all participants in the CPT-only and WAT+CPT testing sessions. Celeration line slopes were compared between testing sessions using paired t-tests. No differences were identified for recovery slopes for HR (p = .295), diastolic BP (p = .300), and relative V̇O2 (p = .176) when comparing CPT-only and WAT+CPT testing sessions. Our results suggest that the CPT elicits a CV and metabolic response beyond that elicited solely by an acute bout of anaerobic exercise. As such, the CPT may be able to serve as a surrogate test for anaerobic exercise for individuals where high-intensity exercise may be contraindicated. Future research is warranted however, as the specific physiological mechanisms governing the observed responses have yet to be elucidated. [ABSTRACT FROM AUTHOR]

Harness hang syncope (HHS) is a risk that specifically affects safety of harness users in mountain climbing. Aims: To evaluate individual patterns of breathing resulting from deranged cardiovascular reflexes triggering a syncopal event when a mismatch between cerebral O2 demand and supply is present. Results: Forty healthy participants [aged 39.1 (8.2) years] were enrolled in a motionless suspension test while hanging in harness. Respiratory gas exchange values were analyzed to assess the pattern of breathing (EpInWel, respiratory elastic power) and cardiovascular parameters were monitored (BP, blood pressure). Four participants experienced HHS after 30.0 (7.6) minutes, with an early manifestation of loss of control of both a sustainable EpInWel and BP, starting after 10–12 minutes. Among the other participants, two different reactions were observed during suspension: (1) group G1 tolerated 32.7 (11.4) minutes of suspension by a favorable adaptation of the EpInWel and BP parameters and (2) group G2 showed significantly shorter time of suspension 24.0 (10.4) minutes with unfavorable increase in EpInWel and BP. Conclusions: Greater resistance to HHS occurs in people developing less marked fluctuations of both respiratory and cardiovascular reflex responses. Conversely, wider fluctuations both in control of EpInWel and BP were observed in the event of decreased suspension tolerance or in syncopal events. [ABSTRACT FROM AUTHOR]

Excessive sympathoexcitation characterizes the chronic heart failure (CHF) state. An exaggerated cardiac sympathetic afferent reflex (CSAR) contributes to this sympathoexcitation. Prior studies have demonstrated that the CSAR to capsaicin [transient receptor potential (TRP) vanilloid 1 agonist] is exaggerated in CHF animal models. We recently discovered that capsaicin application to the lung visceral pleura in anesthetized, vagotomized, open-chested rats increases mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA). We named this response the pulmonary spinal afferent reflex (PSAR). Due to the similarities between TRP vanilloid 1 and TRP ankyrin 1 (TRPA1) channels as well as the excessive sympathoexcitation of CHF, we hypothesized that stimulation of the CSAR and PSAR with a specific TRPA1 agonist would result in an augmented response in CHF rats (coronary ligation model) compared with sham control rats. In response to a TRPA1 agonist, both CSAR and PSAR in sham rats resulted in biphasic changes in MAP and increases in HR and RSNA 10-12 wk postmyocardial infarction (post-MI). These effects were blunted in CHF rats. Assessment of TRPA1 expression levels in cardiopulmonary spinal afferents by immunofluorescence, quantitative RT-PCR, and Western blot analysis 10-12 wk post-MI all indicates reduced expression in CHF rats but no reduction at earlier time points. TRPA1 protein was reduced in a dorsal root ganglia cell culture model of inflammation and simulated tissue ischemia, raising the possibility that the in vivo reduction of TRPA1 expression was, in part, caused by CHF-related tissue ischemia and inflammation. These data provide evidence that reflex responses to cardiopulmonary spinal afferent TRPA1 stimulation may be attenuated in CHF rather than enhanced. NEW & NOTEWORTHY Excessive sympathoexcitation characterizes chronic heart failure (CHF). The contribution of transient receptor potential ankyrin 1 (TRPA1) channel-mediated reflexes to this sympathoexcitation is unknown. We found that application of TRPA1 agonist to the heart and lung surface resulted in increased heart rate and sympathetic output and a biphasic change in mean arterial pressure in control rats. These effects were attenuated in CHF rats, decreasing the likelihood that TRPA1 channels contribute to cardiopulmonary afferent sensitization in CHF. [ABSTRACT FROM AUTHOR]

Background: Arterial baroreflex (BR) and cerebral autoregulation (CA) are two major regulatory mechanisms that maintain constant cerebral perfusion. Little is known about the interplay between these mechanisms, particularly when considering the effects of ageing or sex.Purpose: We studied the relationship between dynamic CA and BR sensitivity (BRS) in healthy subjects by sex and in different age strata.Methods: 95 healthy adults (52% female), 20-80 years-old, were recruited. Arterial blood pressure (Finometer), 3-lead electrocardiogram and cerebral blood flow velocity in middle cerebral arteries (transcranial Doppler) were monitored. We assessed CA by transfer function analysis and BRS in frequency and time domain.Results: With increasing age, BRS diminished (ANCOVA R2 = 0.281, p < 0.001) but CA parameters did not change significantly (p > 0.05). Overall, there was an inverse relationship between the efficacy of BRS and CA low-frequency gain [multivariate linear regression β = 0.41 (0.31; 0.61), p < 0.001]. However, this association suffers changes with ageing: in older subjects BRS and CA were not correlated [β = 0.10 (- 0.41; 0.62), p = 0.369]. Instead, decreasing systolic blood pressure correlated with less efficient CA [lower CA low-frequency gain β = - 0.02 (- 0.03; - 0.02), p = 0.003]. Sex did not affect BRS and CA relationship.Conclusions: Cerebral blood supply is governed by a tuned balance between BR and CA which is lost with age as BRS decreases dramatically. Low systolic blood pressure values might be harmful to older subjects as they might reduce the ability to keep cerebral blood flow tightly controlled. [ABSTRACT FROM AUTHOR]

Electroacupuncture (EA) point specific (ST36-37) stimulation decreases cardiovascular reflex responses through supraspinal regions such as the hypothalamic paraventricular nucleus (PVN) while mechanical stimulation of acupoints decreases pressor responses through peripheral thermal transient receptor potential vanilloid type-1 (TRPV1). Moxibustion generating heat applied at acupoint in combination with antihypertensive drugs decreases elevated blood pressure. We hypothesized that moxibustion modulates sympathoexcitatory cardiovascular responses through the hypothalamic PVN and peripheral heat sensitive TRPV1 in the absence of antihypertensive drugs. Rats were anesthetized, ventilated, and heart rate and mean blood pressure were monitored. Gastric distention induced consistent pressor reflex responses every 10-min. Thirty-minutes of bilateral moxibustion at the acupoint ST36, overlying the deep peroneal nerves, reduced the gastric distention evoked elevation in blood pressure. Blood pressure reflex responses were not reduced by both EA and moxibustion at G39. The moxibustion inhibition but not EA inhibition of the cardiovascular responses was reversed with blockade of local heat sensitive TRPV1 at ST36. Accordingly, activation of thermal TRPV1 by moxibustion at an average of 44.2°C in contrast to 40°C reduced the pressor responses. Naloxone, an opioid receptor antagonist, microinjected into PVN inhibited transiently the effect of moxibustion. Thus, activation of peripheral heat sensitive TRPV1 mediated the moxibustion-inhibition, but not EA-inhibition, of sympathoexcitatory cardiovascular reflex responses through hypothalamic PVN opioid system. [ABSTRACT FROM AUTHOR]

Ojective: To investigate cardiovascular and sudomotor autonomic functions in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) during wakefulness compared to patients with Parkinson's disease (PD) and healthy subjects.Methods: Drug-naïve iRBD patients, PD patients and healthy controls underwent cardiovascular function tests including head-up tilt test (HUTT), Valsalva maneuver, deep breathing, hand grip, and cold face. Heart rate variability (HRV) analysis was performed in the frequency domain using an autoregressive algorithm in the rest supine condition and during HUTT. Sudomotor function was assessed through Sudoscan.Results: Fourteen iRBD patients, 17 PD patients and 12 healthy controls were included in the study. In the supine resting condition, the baseline values of systolic and diastolic blood pressure and heart rate were comparable in all groups. At Valsalva maneuver, iRBD patients and PD patients showed an overshoot which was significantly lower than controls. In addition, iRBD patients showed a significant reduction of sinus arrhythmia at deep breathing compared to controls. Cardiovascular responses to cold face were similar in the three groups while isometric handgrip was significantly reduced in PD patients with respect to healthy subjects. Spectral analysis of HRV showed no significant differences among iRBD, PD patients and controls in the supine resting condition; whereas during HUTT the low-frequency (LF) component of HRV was significantly higher in controls with respect to iRBD and the high-frequency (HF) component was significantly higher in iRBD patients compared to controls. In addition, a significant increase in the LF/HF ratio in healthy subjects was detected compared to iRBD. Finally, four out of 14 iRBD patients (29%) and nine of 17 PD patients (53%) had a sudomotor dysfunction.Conclusions: Our findings obtained in de novo iRBD and PD patients indicate that some alterations of the autonomic nervous system are shared by both groups of patients, reinforcing the close link between the two pathologies, and show an autonomic fragility during wakefulness in iRBD that mainly arises under stress conditions. [ABSTRACT FROM AUTHOR]

Background This review summarizes current knowledge about cardiovascular reflex tests (CVRTs) and other selected autonomic nervous system (ANS) assessment tests in systemic lupus erythematosus (SLE) patients and assesses their clinical utility in this group of patients. Methods The PubMed database was searched for terms associated with CVRTs and SLE. Only papers available in full text and published in English were considered. Ultimately, 13 were selected and analyzed. Results In most of the studies CVRTs results were reported more likely to be abnormal in patients with SLE when compared with controls. The reported prevalence of ANS dysfunction in SLE, diagnosed using CVRTs, ranged from 23.5% to 82.7% of patients, likely because of different definitions of ANS dysfunction, variability in methods of performing CVRTs, and potential confounding factors. In general CVRTs results did not correlate with SLE activity or disease duration, but some CVRTs results correlated with some peptides associated with ANS function, including neuropeptide Y and vasoactive intestinal peptide. Conclusion Patients with SLE generally have abnormal or borderline results of CVRTs, which indicate prevalent abnormalities of the ANS in SLE. Performance of CVRTs requires good standardization of test conditions and familiarity with the proper administration and interpretation of these tests. [ABSTRACT FROM AUTHOR]

Abstract Purpose The aim of the study was to assess cardiac and autonomic function in patients with Crohn's disease and explore their relation to disease duration using cardiovascular reflex tests. Materials and methods Cardiovascular parameters, baroreflex sensitivity, spectral-indices of short-term heart rate variability and blood pressure variability were compared between patients with Crohn's disease in remission (n = 30) and a control group (n = 29). Cardiac autonomic function was assessed during response to standing (tilt) and deep breathing test (expiration/inspiration ratio-E/I). Aortic pulse wave velocity, aortic augmentation index and central systolic blood pressure were measured oscillometrically. Results At rest, Crohn's disease patients had significantly higher systolic (p = 0.03) and diastolic (p = 0.03) blood pressure, total peripheral resistance index (p = 0.003), sympathetic-parasympathetic ratio (p = 0.033) and lower baroreceptor effectiveness (p = 0.047), myocardial variables (stroke index; p = 0.03, cardiac index; p = 0.025, Heather index; p = 0.039, left ventricular ejection time; p = 0.038), as compared to controls. Orthostatic response to the tilt test in the Crohn's disease group and the control group was similar, no intergroup differences were observed for E/I ratio and autonomic parameters. In Crohn's disease patients, disease duration was negatively associated with baroreflex sensitivity and positively correlated with normalised high frequency heart rate variability, sympathetic-parasympathetic ratio at rest and post-tilt changes in Δsystolic blood pressure, p < 0.05. The control group had significantly lower central systolic blood pressure (p = 0.043) compared to Crohn's disease patients. Conclusions Crohn's disease patients in remission have preserved cardiac and autonomic function in response to cardiovascular reflex tests with a shift in cardiovascular autonomic regulation towards sympathetic predominate in the rest position. [ABSTRACT FROM AUTHOR]

Background:-Obesity is a nutritional health problem, which is a potential risk factor for cardiovascular morbidity and mortality and it is gradually rising and affecting a major section of adult population. Altered parasympathetic activity may be considered as a risk factor for obesity and vice versa. Material and method:- The present study is an attempt to pinpoint the defect (if any) in the activity of parasympathetic limb of the autonomic nervous system (ANS) in obesity. Total 80 subjects belonging to the age group of 18-60 years were recruited for the study. The participants were divided into two groups as non obese and obese based body mass index (BMI). The functioning of parasympathetic autonomic nervous system was evaluated by 4 non invasive cardiovascular reflex tests- Resting heart rate,30:15 ratio, expiration/inspiration ratio (E/I ratio) and valsalva maneuver Results:-In the present study, the resting heart rate (beats/minute) was insignificantly (p>0.05) higher in obese subjects and lower values of Expiration/inspiration ratio, 30:15 Ratio and Valsalva Ratio were found in obese subjects when compared to normal weight subjects indicating reduced vagal or parasympathetic activity. Statistically result of Expiration/inspiration ratio and 30:15 Ratio showed significant results (p-value<0.05) and on the other side result of valsalva maneuver showed statistically insignificant result(p-value>0.05).Conclusion:-So from our study it may concluded that there is need of early interventional programs (weight reduction, life style changes and physical exercise) to prevent obesity related cardiovascular sequel in future. [ABSTRACT FROM AUTHOR]

Abstract: The sensory innervation of the lung is well known to be innervated by nerve fibers of both vagal and sympathetic origin. Although the vagal afferent innervation of the lung has been well characterized, less is known about physiological effects mediated by spinal sympathetic afferent fibers. We hypothesized that activation of sympathetic spinal afferent nerve fibers of the lung would result in an excitatory pressor reflex, similar to that previously characterized in the heart. In this study, we evaluated changes in renal sympathetic nerve activity (RSNA) and hemodynamics in response to activation of TRPV1‐sensitive pulmonary spinal sensory fibers by agonist application to the visceral pleura of the lung and by administration into the primary bronchus in anesthetized, bilaterally vagotomized, adult Sprague‐Dawley rats. Application of bradykinin (BK) to the visceral pleura of the lung produced an increase in mean arterial pressure (MAP), heart rate (HR), and RSNA. This response was significantly greater when BK was applied to the ventral surface of the left lung compared to the dorsal surface. Conversely, topical application of capsaicin (Cap) onto the visceral pleura of the lung, produced a biphasic reflex change in MAP, coupled with increases in HR and RSNA which was very similar to the hemodynamic response to epicardial application of Cap. This reflex was also evoked in animals with intact pulmonary vagal innervation and when BK was applied to the distal airways of the lung via the left primary bronchus. In order to further confirm the origin of this reflex, epidural application of a selective afferent neurotoxin (resiniferatoxin, RTX) was used to chronically ablate thoracic TRPV1‐expressing afferent soma at the level of T1–T4 dorsal root ganglia pleura. This treatment abolished all sympatho‐excitatory responses to both cardiac and pulmonary application of BK and Cap in vagotomized rats 9–10 weeks post‐RTX. These data suggest the presence of an excitatory pulmonary chemosensitive sympathetic afferent reflex. This finding may have important clinical implications in pulmonary conditions inducing sensory nerve activation such as pulmonary inflammation and inhalation of chemical stimuli. [ABSTRACT FROM AUTHOR]

Abstract: Binge drinking is widespread on American college campuses, but its effects on the cardiovascular system are poorly understood. This study sought evidence of preclinical cardiovascular changes in binge drinking young adults (n = 24) compared to nondrinking (n = 24) and social drinking (n = 23) peers during baseline, paced sighing (0.033 Hz), and paced breathing (0.1 Hz) tasks. Binge drinkers showed consistent but often statistically nonsignificant evidence of greater sympathetic activation and reduced baroreflex sensitivity. Interestingly, the structure of group‐averaged baseline heart rate spectra was considerably different between groups in the low frequency range (0.05–0.15 Hz). In particular, the binge drinking group–averaged spectra showed several spectral peaks not evident in the other groups, possibly indicating two functionally distinct subranges (0.05–0.08 and 0.08–0.15 Hz) that reflect vascular tone baroreflex activity and heart rate baroreflex activity, respectively. Vascular tone baroreflex gain and power in two peaks in the 0.05–0.08 Hz range were associated with years of drinking in the binge drinking group. Vascular dysfunction may be an early indicator of drinking‐related change in the cardiovascular system. [ABSTRACT FROM AUTHOR]

We have shown that acupuncture, including manual and electroacupuncture (MA and EA), at the P5-6 acupoints stimulates afferent fibers in the median nerve (MN) to modulate sympathoexcitatory cardiovascular reflexes through central regulation of autonomic function. However, the mechanisms underlying acupuncture activation of these sensory afferent nerves and their cell bodies in the dorsal root ganglia (DRG) are unclear. Transient receptor potential vanilloid type 1 (TRPV1) is present in sensory nerve fibers distributed in the general region of acupoints like ST36 and BL 40 located in the hindlimb. However, the contribution of TRPV1 to activation of sensory nerves by acupuncture, leading to modulation of pressor responses, has not been studied. We hypothesized that TRPV1 participates in acupuncture's activation of sensory afferents and their associated cell bodies in the DRG to modulate pressor reflexes. Local injection of iodoresiniferatoxin (Iodo-RTX; a selective TRPV1 antagonist), but not 5% DMSO (vehicle), into the P6 acupoint on the forelimb reversed the MA's inhibition of pressor reflexes induced by gastric distension (GD). Conversely, inhibition of GD-induced sympathoexcitatory responses by EA at P5-6 was unchanged after administration of Iodo-RTX into P5-6. Single-unit activity of Group III or IV bimodal afferents sensitive to both mechanical and capsaicin stimuli responded to MA stimulation at P6. MA-evoked activity was attenuated significantly (P < 0.05) by local administration of Iodo-RTX (n = 12) but not by 5% DMSO (n = 12) into the region of the P6 acupoint in rats. Administration of Iodo-RTX into P5-6 did not reduce bimodal afferent activity evoked by EA stimulation (n = 8). Finally, MA at P6 and EA at P5-6 induced phosphorylation of extracellular signal-regulated kinases (ERK; an intracellular signaling messenger involved in cellular excitation) in DRG neurons located at C7-8 spinal levels receiving MN inputs. After TRPV1 was knocked down in the DRG at these spinal levels with intrathecal injection of TRPV1-siRNA, expression of phosphorylated ERK in the DRG neuron was reduced in MA-treated, but not EA-treated animals. These data suggest that TRPV1 in Group III and IV bimodal sensory afferent nerves contributes to acupuncture inhibition of reflex increases in blood pressure and specifically plays an important role during MA but not EA. [ABSTRACT FROM AUTHOR]

Although it is well-established that severe poisoning by organophosphorus (OP) compounds strongly affects the cardiorespiratory system, the effects of sub-lethal exposure to these compounds on the neural control of cardiovascular function are poorly explored. The aim of this study was to evaluate the effects of acute sub-lethal exposure to chlorpyrifos (CPF), a commonly used OP insecticide, on three basic reflex mechanisms involved in blood pressure regulation, the peripheral chemoreflex, the baroreflex and the Bezold-Jarisch reflex. Adult male Wistar rats were injected intraperitoneally with a single dose of CPF (30 mg/kg) or saline (0.9%). 24 h after injections, cardiovascular reflexes were tested in awake rats. Potassium cyanide (KCN) and phenylbiguanide (PBG) were injected intravenously to activate the chemoreflex and the Bezold-Jarisch reflex, respectively. The baroreflex was activated by phenylephrine and sodium nitroprusside infusions. Blood samples were taken for measurements of butyrylcholinesterase (BChE) activity while acetylcholinesterase (AChE) activity was measured in brainstem samples. Animals treated with CPF presented signs of intoxication such as ataxia, tremor, lacrimation, salivation, tetany, urination and defecation. The hypertensive and the bradycardic responses of the chemoreflex as well as the hypotensive and bradycardic responses of the Bezold-Jarisch reflex were attenuated in CPF treated animals (P < 0.05). Concerning the baroreflex responses, CPF treatment reduced the bradycardia plateau, the range and the gain of the reflex (P < 0.05). Plasma BChE and brainstem AChE were both reduced significantly after CPF treatment (P < 0.05). Our results showed that acute sub-lethal exposure to CPF impairs the cardiovascular responses of homeostatic and defensive cardiovascular reflexes. These effects are associated with a marked inhibition of plasma BChE and brainstem AChE. [ABSTRACT FROM AUTHOR]

Objective: This study is aimed at evaluating whether Continuous Positive Airway Pressure treatment (CPAP) may affect autonomic nervous system (ANS) in male patients with severe obstructive sleep apnea (OSAS).Methods: We compared autonomic symptoms of de novo severe OSAS patients, OSAS patients on chronic CPAP treatment and healthy controls, using the Scales for Outcome in Parkinson disease-Autonomic (SCOPA-AUT) questionnaire. All groups underwent cardiovascular function tests including head-up tilt test (HUTT), Valsalva maneuver, deep breathing, hand grip and cold face tests. Statistical significance was set at p < 0.05.Results: Twelve de novo severe OSAS patients, 17 male OSAS on CPAP and 14 controls were studied. The mean SCOPA-AUT total score was significantly higher in de novo OSAS patients compared with controls. Regarding the distinct domains, both de novo OSAS and CPAP group had abnormalities in respect of controls in urinary sphere. In supine rest condition the baseline values of systolic blood pressure were significantly increased in untreated OSAS patients compared with controls, whereas the basal values of diastolic blood pressure were significantly higher in CPAP patients with respect to controls. After ten min of HUTT, diastolic blood pressure changes were significantly higher in controls compared to both OSAS groups. Untreated OSAS patients showed significant different responses at deep breathing compared to controls. Both OSAS groups had a significant reduction of reflex bradycardia at cold face test.Conclusions: Our study shows that both treated and untreated OSAS patients complain of subjective autonomic symptoms like other sleep disorders reinforcing the close relationship between sleep and autonomic activity. Furthermore, cardiovascular reflexes indicate a tendency to hypertension and a reduced sensitivity to stimuli during wakefulness even in OSA patients on CPAP treatment, suggesting potentially permanent autonomic function deficits. [ABSTRACT FROM AUTHOR]

Lanfranconi, Francesca, Luca Pollastri, Giovanni Corna, Manuela Bartesaghi, Massimiliano Novarina, Alessandra Ferri, and Giuseppe Andrea Miserocchi. The elusive path of brain tissue oxygenation and cerebral perfusion in harness hang syncope in mountain climbers. High Alt Med Biol. 18:363-371, 2017. Aim: Harness hang syncope (HHS) is a risk that specifically affects wide ranges of situations requiring safety harnesses in mountains. An irreversible orthostatic stasis could lead to death if a prompt rescue is not performed. We aimed at evaluating the risk of developing HHS and at identifying the characteristics related to the pathogenesis of HHS. Results: Forty adults (aged 39.1 [8.2] years) were enrolled in a suspension test lasting about 28.7 (11.4) minutes. We measured cardiovascular parameters, and near infrared spectroscopy (NIRS) was used to assess cerebral hypoxia by changes in the concentration of oxyhemoglobin (Δ[HbO2]) and de-oxyhemoglobin (Δ[HHb]). In the four participants who developed HHS: (1) systolic and diastolic blood pressure showed ample oscillations with a final abrupt drop (∼30 mmHg); (2) Δ[HbO2] increased after 8-12 minutes of suspension and reached a plateau before HHS; and (3) Δ[HHb] decreased with a final abrupt increase before syncope. Conclusions: Participants who developed HHS failed to activate cardiovascular reflexes that usually safeguard O2 availability to match the metabolic needs of the brain tissue. Since cerebral hypoxia was detected as an early phenomenon by Δ[HbO2] and Δ[HHb] changes, NIRS measurement appears to be the most important parameter to monitor the onset of HHS. [ABSTRACT FROM AUTHOR]

Purpose Ross syndrome (RS) is characterized by selective involvement of post-ganglionic skin sympathetic nerve fibres. We report a follow-up study in 4 patients to clarify whether in RS autonomic dysfunction spreads affecting also cardiovascular system. Methods The patients underwent cardiovascular reflexes (CVR) and microneurography recording of muscle sympathetic nerve activity (MSNA) for a follow-up mean period of 5 years. Results CVR and MSNA were normal at baseline and unchanged over the follow-up. Conclusions Cardiovascular autonomic system is spared in RS differently from skin autonomic activity dysfunction which progress over time. However, before drawing any definite conclusion, a large cohort of patients needs to be studied. [ABSTRACT FROM AUTHOR]

Background: The trigeminocardiac reflex (TCR) is defined as sudden onset of parasympathetic dysrhythmias including hemodynamic irregularities, apnea, and gastric hypermotility during stimulation of sensory branches of the trigeminal nerve. Since the first description of the TCR in 1999, there is an ongoing discussion about a more emergent clinical definition. In this work, the author worked out an approach to such an improved definition. Methods: In this study, a grounded theory approach was used. Literature about TCR was systematically identified through PubMed (MEDLINE), EMBASE (Ovid SP), and ISI Web of Sciences databases from 1/2005 until 8/2015. TCR was defined as a drop of heart rate (HR) below 60 bpm or 20% to the baseline. A grounded theory approach was used to analyze and interpret the data through a synthesis by the researcher's perspectives, values, and positions. Results: Out of the included studies, the authors formed available data to an update of the understanding of changes in hemodynamic parameters (HR and blood pressure) in a TCR. According to this update, an HR deceleration should be a constant observation to identify a TCR episode while a drop in blood pressure should probably not being fixed to a certain percentage of decrease. Conclusion: The here presented working definition improves our understanding of the TCR. It leads the way to a new understanding of the TCR for a proper clinical definition. [ABSTRACT FROM AUTHOR]

Key points Patients with post-traumatic stress disorder (PTSD) are at a significantly higher risk of developing hypertension and cardiovascular disease. The mechanisms underlying this increased risk are not known., Studies have suggested that PTSD patients have an overactive sympathetic nervous system (SNS) that could contribute to cardiovascular risk; however, sympathetic function has not previously been rigorously evaluated in PTSD patients., Using direct measurements of sympathetic nerve activity and pharmacological manipulation of blood pressure, we show that veterans with PTSD have augmented SNS and haemodynamic reactivity during both combat-related and non-combat related mental stress, impaired sympathetic and cardiovagal baroreflex sensitivity, and increased inflammation., Identifying the mechanisms contributing to increased cardiovascular (CV) risk in PTSD will pave the way for developing interventions to improve sympathetic function and reduce CV risk in these patients., Abstract Post-traumatic stress disorder (PTSD) is associated with increased cardiovascular (CV) risk. We tested the hypothesis that PTSD patients have augmented sympathetic nervous system (SNS) and haemodynamic reactivity during mental stress, as well as impaired arterial baroreflex sensitivity (BRS). Fourteen otherwise healthy Veterans with combat-related PTSD were compared with 14 matched Controls without PTSD. Muscle sympathetic nerve activity (MSNA), continuous blood pressure (BP) and electrocardiography were measured at baseline, as well as during two types of mental stress: combat-related mental stress using virtual reality combat exposure (VRCE) and non-combat related stress using mental arithmetic (MA). A cold pressor test (CPT) was administered for comparison. BRS was tested using pharmacological manipulation of BP via the Modified Oxford technique at rest and during VRCE. Blood samples were analysed for inflammatory biomarkers. Baseline characteristics, MSNA and haemodynamics were similar between the groups. In PTSD vs. Controls, MSNA (+8.2 ± 1.0 vs. +1.2 ± 1.3 bursts min-1, P < 0.001) and heart rate responses (+3.2 ± 1.1 vs. −2.3 ± 1.0 beats min-1, P = 0.003) were significantly augmented during VRCE. Similarly, in PTSD vs. Controls, MSNA (+21.0 ± 2.6 vs. +6.7 ± 1.5 bursts min-1, P < 0.001) and diastolic BP responses (+6.3 ± 1.0 vs. +3.5 ± 1.0 mmHg, P = 0.011) were significantly augmented during MA but not during CPT ( P = not significant). In the PTSD group, sympathetic BRS (-1.2 ± 0.2 vs. -2.0 ± 0.3 burst incidence mmHg−1, P = 0.026) and cardiovagal BRS (9.5 ± 1.4 vs. 23.6 ± 4.3 ms mmHg−1, P = 0.008) were significantly blunted at rest. PTSD patients had significantly higher highly sensitive-C-reactive protein levels compared to Controls (2.1 ± 0.4 vs. 1.0 ± 0.3 mg L−1, P = 0.047). Augmented SNS and haemodynamic responses to mental stress, blunted BRS and inflammation may contribute to an increased CV risk in PTSD. [ABSTRACT FROM AUTHOR]

There is evidence suggesting that exercise training (ET) acts as a factor toward resistance to Trypanosoma cruzi infection. However, the effects of mean arterial pressure (MAP), heart rate (HR), and nitric oxide (NO) during the acute phase of infection has not been elucidated yet. Swiss mice were randomly assigned into four groups: sedentary control (SC, n = 30), trained control (TC, n = 30), sedentary infected (SI, n = 30), and trained infected (TI, n = 30). ET was performed on the treadmill for 9 weeks. After training, the mice were infected with 5 × 10³ trypomastigotes of T. cruzi (Y strain) or PBS. We observed resting bradycardia and improved performance in trained animals compared with sedentary ones. On the 20th day post-infection (DPI), we found a decrease in HR in SI animals compared to TI animals (699.73 ± 42.37 vs. 742.11 ± 25.35 bpm, respectively, P < 0.05). We also observed increased production of NO in cardiac tissue on the 20th DPI in the SI group, normalized in TI group (20.73 ± 2.74 vs. 6.51 ± 1.19μM, respectively). Plasma pro-inflammatory cytokines (IL-12, TNF-α, IFN-γ,) and MCP-1 were increased in SI animals, but decreased in TI animals. The increase in parasitemia on the 15th and 17th DPI in the SI group was attenuated in the TI group. Our results suggest that previous ET plays a preventive role in resistance to T. cruzi infection, modulating cardiovascular aspects, inflammatory reaction, and NO levels of infected mice. [ABSTRACT FROM AUTHOR]

Key points Cardiac sympathetic afferents are considered to be essential pathways for transmission of cardiac nociception to the central nervous system during myocardial ischaemia. However, a potential contribution of the CSAR control of cardiac dysfunction in both normal and chronic heart failure (CHF) states remains unknown., We found that activation of the CSAR evokes little increase in cardiac contractility with an exaggerated peripheral vasoconstriction in the CHF state., CSAR inhibition by epicardial lidocaine decreased cardiac contractility to a greater extent in CHF rats than sham rats. Furthermore, we also found that epicardial lidocaine paradoxically decreased left ventricular end-diastolic pressure (LVEDP) and left ventricular end-diastolic volume (preload) in CHF rats, which was not observed in sham rats., Chronic ablation of the CSAR by epicardial application of the afferent neurotoxin, RTX, selectively lowered diastolic blood pressure CHF rats., The observation suggests that CSAR has a differential effect on cardiac function in normal and CHF states. CSAR activation in normal state causes significant increase in cardiac contractility and cardiac output., Abstract The enhanced 'cardiac sympathetic afferent reflex' (CSAR) critically contributes to the exaggerated global sympathetic tone in chronic heart failure (CHF). However, a potential contribution of the cardio-cardiac reflex control of cardiac function in both normal and CHF states remains unknown. In this study, we evaluated the effects of direct activation or inhibition of the CSAR on cardiac function by pressure-volume ( P-V) loop analysis in ∼12-week sham-operated and myocardial infarcted (MI) rats. In sham rats, acute CSAR activation by epicardial application of bradykinin (BK) increased heart rate (HR), left ventricular systolic pressure (LVSP), the maximum first derivative of left ventricular pressure (d p/d tmax), and the slope of the end-systolic P-V relationship (ESPVR), suggesting that acute CSAR activation in the normal state enhances myocardial contractility. CSAR activation also decreased left ventricular (LV) systolic and diastolic volumes with little effect on LV end-diastolic pressure (LVEDP) or the end-diastolic P-V relationship (EDPVR) in sham rats. Compared to sham, CHF rats exhibit a reduced increase in the slope of the ESPVR and d p/d tmax in response to BK, indicating a poor contractile response to CSAR activation. Interestingly, BK application in CHF rats increased cardiac systolic and diastolic volumes and further increased the elevated LVEDP, neither of which was seen in sham rats. Following CSAR inhibition by epicardial lidocaine, blood pressure, HR, LVSP, d p/d t, LVEDP and ESPVR decreased in CHF rats whereas lidocaine had little effect in sham rats, indicating that the CSAR is tonically active in CHF and contributes to cardiac dysfunction. Furthermore, we found that epicardial lidocaine paradoxically decreased LV end-diastolic volume (preload) in CHF rats, which was not observed in sham rats. The decreased preload by lidocaine in CHF rats may be due to a reduction in peripheral vascular resistance since epicardial lidocaine significantly lowered peripheral (renal) sympathetic nerve activity in CHF rats but not in sham rats. Furthermore, chronic ablation of CSAR by epicardial application of a selective afferent neurotoxin, resiniferatoxin, selectively lowered diastolic blood pressure both at daytime and night-time with less effect on systolic blood pressure in CHF rats. Our data suggest that there is an imbalance between cardiac and peripheral responses to CSAR in CHF animals compared to sham-operated controls. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? Arterial hypertension is associated with impaired neurovascular coupling in the somatosensory cortex. Abnormalities in activity-dependent oxygen consumption in brainstem regions involved in the control of cardiovascular reflexes have not been explored previously., What is the main finding and its importance? Using fast-cyclic voltammetry, we found that changes in local tissue [ABSTRACT FROM AUTHOR]

A low resting heart rate (HR) would be of great benefit in cardiovascular diseases. Ivabradine – a novel selective inhibitor of hyperpolarization-activated cyclic nucleotide gated (HCN) channels– has emerged as a promising HR lowering drug. Its effects on the autonomic HR control are little known. This study assessed the effects of chronic treatment with ivabradine on the modulatory, reflex and tonic cardiovascular autonomic control and on the renal sympathetic nerve activity (RSNA). Male Wistar rats were divided in 2 groups, receiving intraperitoneal injections of vehicle (VEH) or ivabradine (IVA) during 7 or 8 consecutive days. Rats were submitted to vessels cannulation to perform arterial blood pressure (AP) and HR recordings in freely moving rats. Time series of resting pulse interval and systolic AP were used to measure cardiovascular variability parameters. We also assessed the baroreflex, chemoreflex and the Bezold-Jarish reflex sensitivities. To better evaluate the effects of ivabradine on the autonomic control of the heart, we performed sympathetic and vagal autonomic blockade. As expected, ivabradine-treated rats showed a lower resting (VEH: 362 ± 16 bpm vs. IVA: 260 ± 14 bpm, p=0.0005) and intrinsic HR (VEH: 369 ± 9 bpm vs. IVA: 326 ± 11bpm, p=0.0146). However, the chronic treatment with ivabradine did not change normalized HR spectral parameters LF (nu) (VEH: 24.2 ± 4.6 vs. IVA: 29.8 ± 6.4; p>0.05); HF (nu) (VEH: 75.1 ± 3.7 vs. IVA: 69.2 ± 5.8; p>0.05), any cardiovascular reflexes, neither the tonic autonomic control of the HR (sympathovagal index; VEH: 0.91± 0.02 vs. IVA: 0.88 ± 0.03, p=0.3494). We performed the AP, HR and RSNA recordings in urethane-anesthetized rats. The chronic treatment with ivabradine reduced the resting HR (VEH: 364 ± 12 bpm vs. IVA: 207 ± 11 bpm, p

The malnutrition in early life is associated with metabolic changes and cardiovascular impairment in adulthood. Deficient protein intake-mediated hypertension has been observed in clinical and experimental studies. In rats, protein malnutrition also increases the blood pressure and enhances heart rate and sympathetic activity. In this review, we discuss the effects of post-weaning protein malnutrition on the resting mean arterial pressure and heart rate and their variabilities, cardiovascular reflexes sensitivity, cardiac autonomic balance, sympathetic and renin-angiotensin activities and neural plasticity during adult life. These insights reveal an interesting prospect on the autonomic modulation underlying the cardiovascular imbalance and provide relevant information on preventing cardiovascular diseases.

Baroreflex function is usually assessed from spontaneous oscillations of blood pressure (BP) and cardiac RR interval assuming a unidirectional influence from BP to RR. However, the interaction of BP and RR is bidirectional-RR also influences BP. Novel methods based on the concept of Granger causality were recently developed for separate analysis of feedback (baroreflex) and feedforward (mechanical) interactions between RR and BP. We aimed at assessing the proportion of the two causal directions of the interactions between RR and systolic BP (SBP) oscillations during various conditions, and at comparing causality measures from SBP to RR with baroreflex gain indexes. Arterial BP and ECG signals were noninvasively recorded in 16 young healthy volunteers during supine rest, mental arithmetics, and head-up tilt test, as well as during the combined administration of these stressors. The causal interactions between beat-to-beat RR and SBP signals were analyzed in time, frequency, and information domains. The baroreflex gain was assessed in the frequency domain using non-causal and causal measures of the transfer function from SBP to RR. We found a consistent increase in the baroreflex coupling strength from SBP to RR during head-up tilt, an insensitivity of the coupling strength along the non-baroreflex direction to both stressors, and no significant effect of mental arithmetics on the feedback coupling strength. It indicates that the proportion of causal interactions between SBP and RR significantly varies during different conditions. The increase in the coupling from SBP to RR with tilt was not accompanied by concomitant variations of the transfer function gain, suggesting that causality and gain analyses are complementary and assess different aspects of the baroreflex regulation of heart rate. [ABSTRACT FROM AUTHOR]

The trigemino-cardiac reflex (TCR) is a brainstem reflex that manifests as adverse cardiorespiratory events upon the stimulation of sensory branches of the fifth cranial nerve. This reflex is mainly investigated in different neurosurgical procedures and intervention. This reflex is commonly considered as an acute and mild physiological response. On the other hand, more devastating and chronic nature of this reflex is largely underreported and unknown. Therefore, this article aims to provide the comprehensive understanding of the chronic form of TCR, its manifestations, and management by literature search. Also, this paper would certainly impart a better diagnosis and understanding of TCR phenomenon by knowing the relatively less common form of a chronic TCR. This will help thousands and thousands of patients who are still in the phase of diagnosis and are suffering from vague symptoms related to this reflex. [ABSTRACT FROM AUTHOR]

Stimulation of mechanoreceptors in skeletal muscles such as contraction and stretch elicits reflexive autonomic nervous system changes which impact cardiovascular control. There are pressure-sensitive mechanoreceptors in skeletal muscles. Mechanical pressure stimulation of skeletal muscles can induce reflex changes in heart rate (HR) and blood pressure, although the neural mechanisms underlying this effect are unclear. We examined the contribution of cardiac autonomic nerves to HR responses induced by mechanical pressure stimulation (30 s, ~10 N/cm2) of calf muscles in isoflurane-anesthetized rats. Animals were artificially ventilated and kept warm using a heating pad and lamp, and respiration and core body temperature were maintained within physiological ranges. Mechanical stimulation was applied using a stimulation probe 6mm in diameter with a flat surface. Cardiac sympathetic and vagus nerves were blocked to test the contribution of the autonomic nerves. For sympathetic nerve block, bilateral stellate ganglia, and cervical sympathetic nerves were surgically sectioned, and for vagus nerve block, the nerve was bilaterally severed. In addition, mass discharges of cardiac sympathetic efferent nerve were electrophysiologically recorded. Mechanical stimulation increased or decreased HR in autonomic nerve-intact rats (range: -56 to +10 bpm), and the responses were negatively correlated with pre-stimulus HR (r = -0.65, p = 0.001). Stimulation-induced HR responses were markedly attenuated by blocking the cardiac sympathetic nerve (range: -9 to +3 bpm, p < 0.0001) but not the vagus nerve (range: -75 to +30 bpm, p = 0.17). In the experiments with cardiac sympathetic efferent nerve activity recordings, mechanical stimulation increased, or decreased the frequency of sympathetic nerve activity in parallel with HR (r = 0.77, p = 0.0004). Furthermore, the changes in sympathetic nerve activity were negatively correlated with its tonic level (r = -0.62, p = 0.0066). These results suggest that cardiac sympathetic nerve activity regulates HR responses to muscle mechanical pressure stimulation and the direction of HR responses depends on the tonic level of the nerve activity, i.e., bradycardia occurs when the tonic activity is high and tachycardia occurs when the activity is low. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? In this study, we sought to investigate whether cardiovascular responses to peripheral chemoreflex activation of rats recovered from protein restriction are related to activation of AT1 receptors., What is the main finding and its importance? This study highlights the fact that angiotensinergic mechanisms activated by AT1 receptors do not support increased responses to peripheral chemoreflex activation by KCN in rats recovered from protein restriction. Also, we found that protein restriction led to increased resting ventilation in adult rats, even after recovery., The effects of a low-protein diet followed by recovery on cardiorespiratory responses to peripheral chemoreflex activation were tested before and after systemic angiotensin II type 1 (AT1) receptor antagonism. Male Fischer rats were divided into control and recovered (R-PR) groups after weaning. The R-PR rats were fed a low-protein (8%) diet for 35 days and recovered with a normal protein (20%) diet for 70 days. Control rats received a normal protein diet for 105 days (CG105). After cannulation surgery, mean arterial pressure, heart rate, respiratory frequency, tidal volume and minute ventilation were acquired using a digital recording system in freely moving rats. The role of angintensin II was evaluated by systemic antagonism of AT1 receptors with losartan (20 mg kg−1 i.v.). The peripheral chemoreflex was elicited by increasing doses of KCN (20-160 μg kg min−1, i.v.). At baseline, R-PR rats presented increased heart rate and minute ventilation (372 ± 34 beats min−1 and 1.274 ± 377 ml kg−1 min−1) compared with CG105 animals (332 ± 22 beats min−1 and 856 ± 112 ml kg−1 min−1). Mean arterial pressure was not different between the groups. Pressor and bradycardic responses evoked by KCN (60 μg kg−1) were increased in R-PR (+45 ± 13 mmHg and −77 ± 47 beats min−1) compared with CG105 rats (+25 ± 17 mmHg and −27 ± 28 beats min−1), but no difference was found in the tachypnoeic response. These differences were preserved after losartan. The data suggest that angiotensin II acting on AT1 receptors may not be associated with the increased heart rate, increased minute ventilation and acute cardiovascular responses to peripheral chemoreflex activation in rats that underwent postweaning protein restriction followed by recovery. [ABSTRACT FROM AUTHOR]

Objective Autonomic dysfunction occurs in rheumatoid arthritis (RA). However, the association between the autonomic dysfunction and inflammation has not been investigated in RA. We investigated the relationship between inflammation and ANS function in RA. Methods In this cross-sectional study, 25 RA patients and 25 age and sex-matched healthy controls were recruited. Autonomic function assessed by five cardiovascular reflex tests according to Ewing. Parasympathetic dysfunction established by applying three tests: heart rate response to deep breath (HRD) and standing (HRS) and Valsalva tests. Sympathetic dysfunction examined by applying two tests: BP response to standing and handgrip test. Peripheral sympathetic autonomic function assessed by Sudoscan through measurement of electrochemical skin conductance of hands and feet. Sudoscan investigates the sweat gland activity and used as a surrogate to study the damage of sympathetic sudomotor nerves in neuropathy. It is an indirect assessment tool of sudomotor function. Disease-specific and inflammatory measures (DAS 28, ESR, CRP, TNF-α, IL-6 and IL-1) were determined. Results RA patients had significantly impaired HRD, HRS, BP response to hand grip and sudomotor function as compared to healthy controls. Pro-inflammatory cytokines were significantly higher in RA as compared to healthy controls ( p < 0.05). DAS 28 significantly correlated with HRD in RA. ESR significantly correlated with HRD and HRS. TNF-α significantly correlated with HRD, HRS, BP response to standing and sudomotor function. Significant correlation was found between IL-6 and HRS. Seropositive patients had more pronounced CAN and sudomotor dysfunction. Conclusion Autonomic dysfunction in RA is related to disease activity, seropositivity and pro-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

This brief review, which is based on a lecture presented at the American Physiological Society Teaching Refresher Course on the Brain and Systems Control as part of the Experimental Biology meeting in 2015, aims to summarize current concepts of the principal mechanisms in the brain that regulate the autonomic outflow to the cardiovascular system. Such cardiovascular regulatory mechanisms do not operate in isolation but are closely coordinated with respiratory and other regulatory mechanisms to maintain homeostasis. The brain regulates the cardiovascular system by two general means: 1) feedforward regulation, often referred to as "central command," and 2) feedback or reflex regulation. In most situations (e.g., during exercise, defensive behavior, sleep, etc.), both of these general mechanisms contribute to overall cardiovascular homeostasis. The review first describes the mechanisms and central circuitry subserving the baroreceptor, chemoreceptor, and other reflexes that work together to regulate an appropriate level of blood pressure and blood oxygenation and then considers the brain mechanisms that defend the body against more complex environmental challenges, using dehydration and cold and heat stress as examples. The last section of the review considers the central mechanisms regulating cardiovascular function associated with different behaviors, with a specific focus on defensive behavior and exercise. [ABSTRACT FROM AUTHOR]

This study evaluated the effects of the isolated use of a low dose of methyltestosterone ( MT) on cardiovascular reflexes and hormonal levels and its geno- and cytotoxic safety in ovariectomized rats. Female Wistar rats were divided into four groups ( n = 6), respectively: SHAM (received vehicle methylcellulose 0.5%), SHAM + MT (received MT 0.05 mg/kg), OVX (received vehicle), and OVX + MT (received MT). Twenty-one days after ovariectomy, treatment was given orally daily for 28 days. The Bezold-Jarisch reflex ( BJR) was analyzed by measuring the bradycardic and hypotensive responses elicited by phenylbiguanide ( PBG) administration. The baroreflex sensitivity ( BRS) was evaluated by phenylephrine and sodium nitroprussite. Myocyte hypertrophy was determined by morphometric analysis of H&E stained slides. Biochemical data were analyzed, as well as micronucleus assay. MT improved BRS and increased testosterone values, but did not change estradiol in the OVX group. MT did not promote changes in mean arterial pressure, heart rate, BJR, serum concentrations of troponin I, weight and histopathology of the heart. MT was able to restore the BRS in OVX rats. The geno- and cytotoxic safety of the MT was demonstrated by the absence of an increase in the micronucleus ( PCEMN) or change in the ratio between normochromatic erythrocytes and polychromatic erythrocytes ( NCE/ PCE). [ABSTRACT FROM AUTHOR]

A low resting heart rate (HR) would be of great benefit in cardiovascular diseases. Ivabradine-a novel selective inhibitor of hyperpolarization-activated cyclic nucleotide gated (HCN) channels- has emerged as a promising HR lowering drug. Its effects on the autonomic HR control are little known. This study assessed the effects of chronic treatment with ivabradine on the modulatory, reflex and tonic cardiovascular autonomic control and on the renal sympathetic nerve activity (RSNA). Male Wistar rats were divided in 2 groups, receiving intraperitoneal injections of vehicle (VEH) or ivabradine (IVA) during 7 or 8 consecutive days. Rats were submitted to vessels cannulation to perform arterial blood pressure (AP) and HR recordings in freely moving rats. Time series of resting pulse interval and systolic AP were used to measure cardiovascular variability parameters. We also assessed the baroreflex, chemoreflex and the Bezold-Jarish reflex sensitivities. To better evaluate the effects of ivabradine on the autonomic control of the heart, we performed sympathetic and vagal autonomic blockade. As expected, ivabradine-treated rats showed a lower resting (VEH: 362 ± 16 bpm vs. IVA: 260 ± 14 bpm, p = 0.0005) and intrinsic HR (VEH: 369 ± 9 bpm vs. IVA: 326 ± 11 bpm, p = 0.0146). However, the chronic treatment with ivabradine did not change normalized HR spectral parameters LF (nu) (VEH: 24.2 ± 4.6 vs. IVA: 29.8 ± 6.4; p > 0.05); HF (nu) (VEH: 75.1 ± 3.7 vs. IVA: 69.2 ± 5.8; p > 0.05), any cardiovascular reflexes, neither the tonic autonomic control of the HR (tonic sympathovagal index; VEH: 0.91± 0.02 vs. IVA: 0.88 ± 0.03, p = 0.3494). We performed the AP, HR and RSNA recordings in urethane-anesthetized rats. The chronic treatment with ivabradine reduced the resting HR (VEH: 364 ± 12 bpm vs. IVA: 207 ± 11 bpm, p < 0.0001), without affecting RSNA (VEH: 117 ± 16 vs. IVA: 120 ± 9 spikes/s, p = 0.9100) and mean arterial pressure (VEH: 70 ± 4 vs. IVA: 77 ± 6 mmHg, p = 0.3293). Our results suggest that, in health rats, the long-term treatment with ivabradine directly reduces the HR without changing the RSNA modulation and the reflex and tonic autonomic control of the heart. [ABSTRACT FROM AUTHOR]

Patients with myocardial infarction experience various types of chest pain and autonomic disturbance symptoms. Studies in rats have shown that pericardial infusions of certain chemicals induce cardiac-related muscle pain and cardiovascular reflexes. In the present study, bradykinin or capsaicin was injected into the pericardial sac and the resulting cardiac-somatic reflexes and blood pressure (BP) alterations were record. We found that the cardiac-somatic reflex induced by bradykinin had a longer latency, shorter duration, and lower firing rate than that induced by capsaicin (p < 0.05). We also found that bradykinin induced a hypertensive response (p < 0.05), while capsaicin induced a hypotensive response (p < 0.05). Bilateral vagotomy had no effect on the cardiac-somatic reflex induced by bradykinin (p > 0.05) but reduced the reflex induced by capsaicin (p < 0.05). However, vagotomy had no effect on the BP alterations induced by both bradykinin and capsaicin (p > 0.05). These results suggest that bradykinin and capsaicin activate different pathways to induce cardiac-somatic and cardiovascular reflexes and that the vagus nerve is involved in TRPV1-related muscle pain modulation. [ABSTRACT FROM AUTHOR]

Ultrasound has become a widely used diagnostic technique. While its role in patient evaluation is well known, its utility during preclinical courses such as anatomy and physiology is becoming increasingly recognized. The aim of the present study was to assess the feasibility/utility of integrating ultrasound-based sessions into conventional undergraduate medical school programs of physiology of the cardiovascular system and cardiovascular reflexes and to evaluate student perceptions of an ultrasound-based didactic session. Second-year medical students enrolled in the University of Padova attended a didactic session during which basic concepts regarding ultrasound instrumentation, image production, and spatial orientation were presented. Five anatomic sectors (the heart, aorta, neck vessels, inferior vena cava, and femoral veins) were then examined on a volunteer. Student perceptions of the images that were projected, the usefulness of the presentation, and the reproducibility of the experience were assessed at the end of the lecture with an anonymous questionnaire consisting of positive and negative items that were rated using a 5-point Likert scale and with two questions. One hundred eleven students attended the lecture; 99% of them found it very interesting, and none considered it boring or a waste of time. More than 96% thought it helped them to gain a better comprehension of the subject and would recommend it to a colleague. In conclusion, as ultrasound has been found to be a valuable resource for the teaching of physiology of the cardiovascular system and cardiovascular reflexes, efforts should be made to integrate ultrasound sessions into the traditional human physiology curriculum. [ABSTRACT FROM AUTHOR]

Muscle sympathetic nerve activity (MSNA) variability is traditionally computed through a low-pass filtering procedure that requires normalization. We proposed a new beat-to-beat MSNA variability computation that preserves dimensionality typical of an integrated neural discharge (i.e., bursts per unit of time). The calibrated MSNA (cMSNA) variability technique is contrasted with the traditional uncalibrated MSNA (ucMSNA) version. The powers of cMSNA and ucMSNA variabilities in the low-frequency (LF, from 0.04 to 0.15 Hz) band were computed with those of the heart period (HP) of systolic and diastolic arterial pressure (SAP and DAP, respectively) in seven healthy subjects (age, 20-28 years; median, 22 years; 5 women) during a graded head-up tilt. Subjects were sequentially tilted at 0°, 20°, 30°, 40°, and 60° table inclinations. The LF powers of ucMSNA and HP variabilities were expressed in normalized units (LFnu), whereas all remaining spectral markers were expressed in absolute units. We found that 1) the LF power of cMSNA variability was positively correlated with tilt angle, whereas the LFnu power of the ucMSNA series was uncorrelated; 2) the LF power of cMSNA variability was correlated with LF powers of SAP and DAP, LFnu power of HP and noradrenaline concentration, whereas the relationship of the LFnu power of ucMSNA variability to LF powers of SAP and DAP was weaker and that to LFnu power of HP was absent; and 3) the stronger relationship of cMSNA variability to SAP and DAP spectral markers compared with the ucMSNA series was confirmed individually. The cMSNA variability appears to be more suitable in describing sympathetic control in humans than traditional ucMSNA variability. [ABSTRACT FROM AUTHOR]

Distension of peripheral veins in humans elicits a pressor and sympathoexcitatory response that is mediated through group III/IV skeletal muscle afferents. There is some evidence that autonomic reflexes mediated by these sensory fibers are blunted with increasing age, yet to date the venous distension reflex has only been studied in young adults. Therefore, we tested the hypothesis that the venous distension reflex would be attenuated in middle-aged compared with young adults. Nineteen young (14 men/5 women, 25 ± 1 yr) and 13 middle-aged (9 men/4 women, 50 ± 2 yr) healthy normotensive participants underwent venous distension via saline infusion through a retrograde intravenous catheter in an antecubital vein during limb occlusion. Beat-by-beat blood pressure, muscle sympathetic nerve activity (MSNA), and model flow-derived cardiac output (Q), and total peripheral resistance (TPR) were recorded throughout the trial. Mean arterial pressure (MAP) increased during the venous distension in both young (baseline 83 ± 2, peak 94 ± 3 mmHg; P < 0.05) and middle-aged adults (baseline 88 ± 2, peak 103 ± 3 mmHg; P < 0.05). MSNA also increased in both groups [young: baseline 886 ± 143, peak 1,961 ± 242 arbitrary units (AU)/min; middle-aged: baseline 1,164 ± 225, peak 2,515 ± 404 AU/min; both P < 0.05]. TPR (P < 0.001), but not Q (P = 0.76), increased during the trial. However, the observed increases in blood pressure, MSNA, and TPR were similar between young and middle-aged adults. Additionally, no correlation was found between age and the response to venous distension (all P > 0.05). These findings suggest that peripheral venous distension elicits a pressor and sympathetic response in middle-aged adults similar to the response observed in young adults. [ABSTRACT FROM AUTHOR]

Acute inhalation of airborne pollutants alters cardiovascular function and evidence suggests that pollutant-induced activation of airway sensory nerves via the gating of ion channels is critical to these systemic responses. Here, we have investigated the effect of capsaicin [transient receptor potential (TRP) vanilloid 1 (TRPV1) agonist], AITC [TRP ankyrin 1 (TRPA1) agonist], and ATP (P2X2/3 agonist) on bronchopulmonary sensory activity and cardiovascular responses of conscious Sprague-Dawley (SD) rats. Single fiber recordings show that allyl isothiocyanate (AITC) and capsaicin selectively activate C fibers, whereas subpopulations of both A and C fibers are activated by stimulation of P2X2/3 receptors. Inhalation of the agonists by conscious rats caused significant bradycardia, atrioventricular (AV) block, and prolonged PR intervals, although ATP-induced responses were lesser than those evoked by AITC or capsaicin. Responses to AITC were inhibited by the TRP channel blocker ruthenium red and the muscarinic antagonist atropine. AITC inhalation also caused a biphasic blood pressure response: a brief hypertensive phase followed by a hypotensive phase. Atropine accentuated the hypertensive phase, while preventing the hypotension. AITC-evoked bradycardia was not abolished by terazosin, the α1-adrenoceptor inhibitor, which prevented the hypertensive response. Anesthetics had profound effects on AITC-evoked bradycardia and AV block, which was abolished by urethane, ketamine, and isoflurane. Nevertheless, AITC inhalation caused bradycardia and AV block in paralyzed and ventilated rats following precollicular decerebration. In conclusion, we provide evidence that activation of ion channels expressed on nociceptive airway sensory nerves causes significant cardiovascular effects in conscious SD rats via reflex modulation of the autonomic nervous system. [ABSTRACT FROM AUTHOR]

The underlying pathophysiology of supraventricular and ventricular arrhythmias remains a matter of intense investigation. Though evolving, the contemporary explanations do not encompass all aspects of arrhythmogenicity. An improved understanding of arrhythmia substrate is needed to augment therapeutic capabilities. Our observation and literature sources demonstrate relatively high incidence of transitory arrhythmias which are non-intentionally generated by the endocardial lead/catheter manipulation. These findings are interesting and potentially may crystallize the reflex-dependent proarrhythmic cardiac activity. Herein we suggest the "reflexogenic arrhythmogenicity" concept extending an overall spectrum of known hypotheses. Cardiovascular reflex action can be categorized into three-tiered levels -intra-cellular, inter-cellular and inter-organic. The first two levels of the triplicate system reside within the cardiac anatomical landmarks (in fact intramurally, intra-organically), however the third one implicates central (cerebral) activity which boomerangs back via centripetal and centrifugal connections. These levels likely compose synoptic ternary reflex set system which may be validated in future studies. To hypothesize, coordinated mutual reciprocity of reflex activity results in stabilization of heart rhythm in robust heart. Any stressful cardiac event may lead to the shift of the rhythm toward unfavorable clinical entity probably via the loss of the influence of dominant reflex. Overall, an interaction and likely intrinsic inter-tiered competition along with possible interplay between physiological and pathological reflexes may be treated as contributing factors for the inception and maintaining of arrhythmias and cardiac performance as well. These assumptions await further documentation. If such a tenet were recognized, the changes in the clinical approach to arrhythmia management might be anticipated, preferably by selective reflex suppression or activation strategy. [ABSTRACT FROM AUTHOR]

Blood pressure is a vital element to maintain circulation and eventually cellular respiration and metabolism. Blood pressure abnormalities are one of the most common diseases worldwide and their prevalence increases with age. For decades, basic and clinical investigations have shown that autonomic dysregulation/imbalance is involved in the development and progression of cardiovascular diseases. Arterial baroreflex is a powerful regulator of blood pressure and sympathetic nervous system. Closed-loop neuromodulation technology focusing on arterial baroreflex is challenging and might be promising to tackle the pathogenesis of blood pressure-related disorders, autonomic dysregulation, and eventually cardiovascular diseases. For more than a decade, we and associates have developed “bionic” baroreflex systems. “Bionic” means that the device is designed to replicate the dynamic characteristics of the native system to fully restore the function. The bionic baroreflex system basically consists of an artificial pressure sensor, a neurostimulator for autonomic nerves and a regulator that encodes blood pressure into neurostimulation. In the process of development toward clinical applicability, researchers have faced logical problems in designing the controller and practical problems of how to approach baroreflex activation. Closed-loop baroreflex systems utilizing sympathetic nerve trunk stimulation, spinal cord stimulation and noninvasive transcutaneous stimulation were proposed. Recently, the bionic baroreceptor was reported and proposed to be a potential therapy for heart failure. In this article, we introduce the closed-loop neuromodulation technology for baroreflex blood pressure control and discuss future direction of development of this technology. [ABSTRACT FROM AUTHOR]

Purpose: The muscle metaboreflex activation has been shown essential to reach normal hemodynamic response during exercise. It has been demonstrated that patients with multiple sclerosis (MS) have impaired autonomic functions and cardiovascular regulation during exercise. However, to the best of our knowledge, no previous research to date has studied the metaboreflex in MS patients. The purpose of this study was to investigate the hemodynamic response to metaboreflex activation in patients with MS (n = 43) compared to an age-matched, control group (CTL, n = 21).Methods: Cardiovascular response during the metaboreflex was evaluated using the post-exercise muscle ischemia (PEMI) method and during a control exercise recovery (CER) test. The difference in hemodynamics between the PEMI and the CER test was calculated and this procedure allowed for the assessment of the metaboreflex response. Hemodynamics was estimated by impedance cardiography.Results: The MS group showed a normal mean blood pressure (MBP) response as compared to the CTL group (+6.5 ± 6.9 vs. +8 ± 6.8 mmHg, respectively), but this response was achieved with an increase in systemic vascular resistance, that was higher in the MS with respect to the CTL group (+137.6 ± 300.5 vs. -14.3 ± 240 dyne · s(-1) cm(-5), respectively). This was the main consequence of the MS group's incapacity to raise the stroke volume (-0.65 ± 10.6 vs. +6.2 ± 12.8 ml, respectively).Conclusion: It was concluded that MS patients have an impaired capacity to increase stroke volume (SV) in response to low level metaboreflex, even if they could sustain the MBP response by vasoconstriction. This was probably a consequence of their chronic physical de-conditioning. [ABSTRACT FROM AUTHOR]