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Heart rate variability (HRV) is a measure of the autonomic nervous system function and possibly related to postoperative outcome. Despite several HRV studies in different surgical settings, optimal indices and timepoints for measuring have not been adequately determined. Consequently, there is a need for detailed descriptive procedure-specific studies on the time-course of perioperative HRV within a modern fast-track surgical setting. We measured HRV continuously in 24 patients from 4 days before until 9 days after total hip arthroplasty (THA). Statistical methods included mainly ANOVA and t-tests or Kruskal–Wallis and pairwise Wilcoxon test. Patients completed the Orthostatic Discriminant and Severity Scale five times during the study describing autonomic nervous system dysfunction. Standard deviation between normal-to-normal beats and the total power of HRV were reduced for at least 9 days following THA, with a trend towards increased HRV leading up to the day of surgery. The balance between low- and high-frequency power of HRV was reduced in the postoperative evenings. There was increased orthostatic intolerance symptoms on the first postoperative day, with symptoms of pain, fatigue and weakness decreasing after the first postoperative day. Median hospital stay was 1 day. We provide the first detailed description of perioperative time-course of HRV and orthostatic symptoms in fast-track THA, showing reduced HRV after surgery for at least a week, and that HRV changes are sensitive to time of day and timing before and after surgery. These results are helpful in designing future HRV studies in perioperative risk assessment and outcome., Heart rate variability (HRV) is a measure of the autonomic nervous system function and possibly related to postoperative outcome. Despite several HRV studies in different surgical settings, optimal indices and timepoints for measuring have not been adequately determined. Consequently, there is a need for detailed descriptive procedure-specific studies on the time-course of perioperative HRV within a modern fast-track surgical setting. We measured HRV continuously in 24 patients from 4 days before until 9 days after total hip arthroplasty (THA). Statistical methods included mainly ANOVA and t-tests or Kruskal–Wallis and pairwise Wilcoxon test. Patients completed the Orthostatic Discriminant and Severity Scale five times during the study describing autonomic nervous system dysfunction. Standard deviation between normal-to-normal beats and the total power of HRV were reduced for at least 9 days following THA, with a trend towards increased HRV leading up to the day of surgery. The balance between low- and high-frequency power of HRV was reduced in the postoperative evenings. There was increased orthostatic intolerance symptoms on the first postoperative day, with symptoms of pain, fatigue and weakness decreasing after the first postoperative day. Median hospital stay was 1 day. We provide the first detailed description of perioperative time-course of HRV and orthostatic symptoms in fast-track THA, showing reduced HRV after surgery for at least a week, and that HRV changes are sensitive to time of day and timing before and after surgery. These results are helpful in designing future HRV studies in perioperative risk assessment and outcome.

Heart rate variability (HRV) is a measure of cardiac autonomic modulation and is potentially related to hypotension, postoperative atrial fibrillation, and orthostatic intolerance. However, there is a lack of knowledge on which specific time points and indices to measure. To improve future study design, there is a need for procedure-specific studies in an enhanced recovery after surgery (ERAS) video-assisted thoracic surgery (VATS) lobectomy setting, and for continuous measurement of perioperative HRV. HRV was measured continuously from 2 days before until 9 days after VATS lobectomy in 28 patients. After VATS lobectomy, with median length of stay = 4 days, the standard deviation between normal-to-normal beats and the total power of HRV were reduced for 8 days during the night and day times, while low-to-high frequency variation and detrended fluctuation analysis were stable. This is the first detailed study to show that HRV measures of total variability were reduced following ERAS VATS lobectomy, while other measures were more stable. Further, preoperative HRV measures showed circadian variation. The patch was well tolerated among participants, but actions should be taken to ensure proper mounting of the measuring device. These results demonstrate a valid design platform for future HRV studies in relation to postoperative outcomes., Heart rate variability (HRV) is a measure of cardiac autonomic modulation and is potentially related to hypotension, postoperative atrial fibrillation, and orthostatic intolerance. However, there is a lack of knowledge on which specific time points and indices to measure. To improve future study design, there is a need for procedure-specific studies in an enhanced recovery after surgery (ERAS) video-assisted thoracic surgery (VATS) lobectomy setting, and for continuous measurement of perioperative HRV. HRV was measured continuously from 2 days before until 9 days after VATS lobectomy in 28 patients. After VATS lobectomy, with median length of stay = 4 days, the standard deviation between normal-to-normal beats and the total power of HRV were reduced for 8 days during the night and day times, while low-to-high frequency variation and detrended fluctuation analysis were stable. This is the first detailed study to show that HRV measures of total variability were reduced following ERAS VATS lobectomy, while other measures were more stable. Further, preoperative HRV measures showed circadian variation. The patch was well tolerated among participants, but actions should be taken to ensure proper mounting of the measuring device. These results demonstrate a valid design platform for future HRV studies in relation to postoperative outcomes.

Patients with severe traumatic brain injury (TBI) may have autonomic dysfunction, one manifestation of which is orthostatic intolerance. This potentially impairs physical rehabilitation. However, the exact mechanisms remain elusive. In 30 patients participating in a trial of early tilt training versus standard care and 15 healthy volunteers, 5-min electrocardiography was recorded in the supine position and during 70° head-up tilt. Heart rate variability was analyzed by the low- and high-frequency (LF and HF) power, the LF-HF ratio, the total power, the ratio of the standard deviation of normal-to-normal intervals (SDNN), the root mean square of successive differences (RMSSD), the detrended fluctuations, and sample entropy. In patients in the upright compared to the supine position, SDNN (p < 0.001), RMSSD (p < 0.001), and total power (p = 0.004) all decreased, while the remaining variables were unchanged; no long-term differences in heart rate variability in the supine position were found between early tilt training and standard care. In the healthy volunteers, all measures besides SDNN and total power changed significantly between supine and upright position. In patients with severe TBI compared to healthy volunteers, several measures of heart rate variability changed differentially during mobilization from the supine to the upright position.

Purpose: Early postoperative mobilization can be hindered by orthostatic intolerance (OI). Postoperative OI has multifactorial pathogenesis, possibly involving both postoperative hypovolemia and autonomic dysfunction. We aimed to investigate the effect of mild acute blood loss from blood donation simulating postoperative hypovolemia, on both autonomic function and OI, thus eliminating confounding perioperative factors such as inflammation, residual anesthesia, pain, and opioids. Methods: This prospective observational cohort study included 26 blood donors. Continuous electrocardiogram data were collected during mobilization and night sleep, both before and after blood donation. A Valsalva maneuver and a standardized mobilization procedure were performed immediately before and after blood donation, during which cardiovascular and tissue oxygenation variables were continuously measured by LiDCOrapid™ and Massimo Root™, respectively. The incidence of OI, hemodynamic responses during mobilization and Valsalva maneuver, as well as heart rate variability (HRV) responses during mobilization and sleep were compared before and 15 min after blood donation. Results: Prior to blood donation, no donors experienced OI during mobilization. After blood donation, 6/26 (23%; 95% CI, 9 to 44) donors experienced at least one OI symptom. Three out of 26 donors (12%; 95% CI, 2 to 30) terminated the mobilization procedure prematurely because of severe OI symptoms. Cardiovascular and cerebral tissue oxygenation responses were reduced in patients with severe OI. After blood loss, HRV indices of total autonomic power remained unchanged but increased sympathetic and decreased parasympathetic outflow was observed during mobilization, but also during sleep, indicating a prolonged autonomic effect of hypovolemia. Conclusion: We describe a specific hypovolemic component of postoperative OI, independent of postoperative autonomic dysfunction, inflammation, opioids, and pain. Study registration

In patients with severe traumatic brain injury, there is limited evidence of the clinical effect of early orthostatic exercise, although such exercise may strengthen systemic or cerebral hemodynamic responses to head-up tilt, thereby minimizing orthostatic intolerance. We measured dynamic cerebral autoregulation (dCA) and the occurrence of orthostatic intolerance after four weeks of regular orthostatic exercise by head-up tilt using a tilt table with integrated stepping using the ERIGO® tilt-table and comparing it to standard care. Thirty-four patients with severe traumatic brain injury admitted to a neurocritical care unit were included in this randomized clinical trial. Middle cerebral artery blood flow velocity (MCAv), non-invasive mean arterial pressure, heart rate and PaCO2 were recorded; dCA was measured by the non-invasive mean flow index (nMxa). Transition from the supine position to head-up tilt triggered a 10–16% decrease in MCAv and increased nMxa in both groups at all time points (P < 0.05), with no differences between groups. There was no difference in the number of episodes with orthostatic intolerance (5 vs 3; 1 vs 2; 1 vs 0) at baseline, two weeks and four weeks, respectively, and no association between changes in PaCO2-adjusted nMxa and the occurrence of orthostatic reactions (P = 0.35). Early orthostatic exercise does not affect dynamic cerebral autoregulation and does not protect against orthostatic intolerance in patients with severe traumatic brain injury. Trial registration: ClinicalTrials.gov identifier: NCT02924649. Registered on 3rd October 2016.

We herein report two new adolescent cases of Bier anemic spots, cyanosis, and urticaria-like eruption (BASCULE) syndrome. This rare, recently described condition may be associated with postural orthostatic tachycardia syndrome (POTS) and other forms of orthostatic intolerance. This report provides details on two cases and a literature review.

Disorders of blood pressure control arise from disruption of the autonomic nervous system and result in symptomatic orthostatic hypotension and large fluctuations in blood pressure. Ambulatory blood pressure monitoring is used in the general population for assessment of blood pressure control and to detect episodes of hypotension. In spinal cord injury (SCI), impaired control of the sympathetic nervous system leads to orthostatic intolerance and autonomic dysreflexia. Smaller studies in restricted populations have examined ambulatory pressures in SCI and observed abnormalities in diurnal blood pressure variation in complete cervical SCI. Altered diurnal blood pressure is associated with abnormalities in diurnal urine production and orthostatic intolerance in autonomic failure. This triad may also occur in SCI to explain the orthostatic intolerance. A retrospective examination of ambulatory pressures of patients with SCI referred for clinically significant blood pressure disorders revealed a high prevalence of abnormalities in diurnal blood pressure and urine production in acute and chronic tetraplegia and in acute paraplegia. To characterise the course of diurnal blood pressure, urine production and orthostatic symptoms in SCI, two prospective studies were performed. First, consecutive patients admitted with acute SCI were screened for recruitment, and consenting volunteers were compared with immobilised and mobilising controls. In the second study, people with chronic SCI (>1 year) living in the community were compared with mobilising controls. Compared with mobilising and immobilised controls, there was a high prevalence of abnormal diurnal blood pressure variation in SCI. The abnormalities were most prevalent and marked in higher and earlier SCI. Abnormalities persisted over time in both complete and incomplete cervical SCI. Abnormalities in high paraplegia were no different to that of cervical SCI in early SCI, but were no different to that of controls in chroni

type:Article, Criative Commons Attribution Licence, Exercise modulates arterial pressure (AP) regulation over various time spans. AP increases at the onset of exercise and this increase is then sustained during exercise. Once exercise is stopped, AP is suppressed for up to an hour afterwards. Prolonged endurance training is associated with dysfunction of the sympathetic regulation of AP in response to posture changes (orthostatic intolerance). Baroreflex control of sympathetic nerve activity (SNA) has been extensively studied to understand the mechanisms underlying exercise-induced changes in AP. We have previously presented entire baroreflex AP-SNA curves during and after exercise, and during central volume expansion, obtained using direct measurements of renal sympathetic nerve activity (RSNA) in conscious animals. In this review, we describe the modulatory effects of exercise on baroreflex control of AP based on these entire AP-RSNA baroreflex curves. We suggest that both acute and chronic exercise can have modulatory effects on the entire baroreflex curve for SNA, and that these effects differ among time periods.

We report results from di¿erent intensive simulations aimed at evaluate the risks involved in a long-term exposure to hypo and hypergravity loads for a very extensive range of possible mission scenarios. The simulation allows us to introduce di¿erent levels of exposure to micro or hypergravity, analyse the consequences on relevant ¿gures of cardiovascular deconditioning, such as heart rate, mean stroke volume or vascular resistance; and evalatue the relative risk of putting a mission into jeopardy due to micrograv-ity deconditioning e¿ects.Thermical stress, aerobic or anaerobic exercise are also simulated to take into account a realistic long-term space mission including, for example, ExtraVehicular Activities (EVA) or physical exercise as countermeasure. Gender di¿erences have been found, with a signi¿cant di¿erence in risk decrement for women compared with that in men, when aerobic exercise is simulated in long-term missions. The model is based on previous works form Melchier et al. or Heldt et al. who described in analytical terms the process of orthostatic intolerance due to gravity alterations being applied ot a subject. We then incorporated these Runge-Kutta equations into a numerical model by using Matlab and Simulink software, to take into account the complex process of deconditioning of the cardiovascular system. Results from these models were validated in parabolic ¿ight. The simulation is based on an electrical-like control system model in which output variables of the body performance (vascular resistance,blood volume etc) are found while step-by-step changes of gravity and thermal stress were applied. Di¿erent micrograivity exposure scenarios, including Moon, Mars and other exploration missions are considered, and their asso-ciated risks are quanti¿ed. The more relevant results are provided, including the ¿nding that the vascular resistance deconditioning appears to be alike in both microgravity and the reduced gravity at the level of the Moon. This dec, Postprint (published version)

[EN] Orthostatic intolerance syndrome occurs when the autonomic nervous system is incapacitated and fails to respond to the demands associated with the upright position. Assessing this syndrome among the elderly population is important in order to prevent falls. However, this problem is still challenging. The goal of this work was to determine the relationship between orthostatic intolerance (OI) and the cardiovascular response to exercise from the analysis of heart rate and blood pressure. More specifically, the behavior of these cardiovascular variables was evaluated in terms of refined composite multiscale fuzzy entropy (RCMFE), measured at different scales. The dataset was composed by 65 older subjects, 44.6% (n = 29) were OI symptomatic and 55.4% (n = 36) were not. Insignificant differences were found in age and gender between symptomatic and asymptomatic OI participants. When heart rate was evaluated, higher differences between groups were observed during the recovery period immediately after exercise. With respect to the blood pressure and other hemodynamic parameters, most significant results were obtained in the post-exercise stage. In any case, the symptomatic OI group exhibited higher irregularity in the measured parameters, as higher RCMFE levels in all time scales were obtained. This information could be very helpful for a better understanding of cardiovascular instability, as well as to recognize risk factors for falls and impairment of functional status.

The calf muscle pump is a mechanism which increases venous return and thereby compensates for the fluid shift towards the lower body during standing. During a muscle contraction, the embedded deep veins collapse and venous return increases. In the subsequent relaxation phase, muscle perfusion increases due to increased perfusion pressure, as the proximal venous valves temporarily reduce the distal venous pressure (shielding). The superficial and deep veins are connected via perforators, which contain valves allowing flow in the superficial-to-deep direction. The aim of this study is to investigate and quantify the physiological mechanisms of the calf muscle pump, including the effect of venous valves, hydrostatic pressure, and the superficial venous system. Using a one-dimensional pulse wave propagation model, a muscle contraction is simulated by increasing the extravascular pressure in the deep venous segments. The hemodynamics are studied in three different configurations: a single artery–vein configuration with and without valves and a more detailed configuration including a superficial vein. Proximal venous valves increase effective venous return by 53% by preventing reflux. Furthermore, the proximal valves shielding function increases perfusion following contraction. Finally, the superficial system aids in maintaining the perfusion during the contraction phase and reduces the refilling time by 37%.

Central hypovolemia elicited by orthostasis or hemorrhage triggers sympathetically-mediated baroreflex responses to maintain organ perfusion; these reflexes are less sensitive in patients with orthostatic intolerance, and during conditions of severe blood loss, may result in cardiovascular collapse (decompensatory or circulatory shock). The ability to tolerate central hypovolemia is variable and physiological factors contributing to tolerance are emerging. We tested the hypothesis that resting muscle sympathetic nerve activity (MSNA) and sympathetic baroreflex sensitivity (BRS) are attenuated in male and female subjects who have low tolerance (LT) to central hypovolemia induced by lower body negative pressure (LBNP). MSNA and diastolic arterial pressure (DAP) were recorded in 47 human subjects who subsequently underwent LBNP to tolerance (onset of presyncopal symptoms). LT subjects experienced presyncopal symptoms prior to completing LBNP of 60mm Hg, and subjects with high tolerance (HT) experienced presyncopal symptoms after completing LBNP of 60mm Hg. Contrary to our hypothesis, resting MSNA burst incidence was not different between LT and HT subjects, and was not related to time to presyncope. BRS was assessed as the slope of the relationship between spontaneous fluctuations in DAP and MSNA during 5 min of supine rest. MSNA burst incidence/DAP correlations were greater than or equal to 0.5 in 37 subjects (LT: n = 9; HT: n = 28), and BRS was not different between LT and HT ( 1.8 0.3 vs. 2.2 0.2 bursts (100 beats) 1 mm Hg 1, p = 0.29). We conclude that tolerance to central hypovolemia is not related to either resting MSNA or sympathetic BRS., Published in Frontiers in Physiology, v5 article 241, Jun 2014. Prepared in collaboration with the University of North Texas Health Science Center, Fort Worth.

Objectives: Many non-musculoskeletal complaints in EDS-HT may be related to dysautonomia. This study therefore aims to investigate whether dysautonomia is present and to explore the underlying mechanisms. Methods: A total of 39 females with EDS-HT and 35 age-matched controls underwent autonomic function testing. Resting autonomic tone was assessed using heart rate variability (frequency domain) and baroreflex sensitivity analysis (cross correlation). Autonomic reactivity was assessed using the Autonomic Reflex Screen test battery. Factors suspected to contribute to dysautonomia, e.g. neuropathy, medication use, decreased physical activity, depression, pain-induced sympathetic arousal, and connective tissue laxity, were quantified using validated questionnaires, the Beighton score, and measurement of skin extensibility. Results: The EDS-HT group showed autonomic deregulation with increased sympathetic activity at rest and reduced sympathetic reactivity to stimuli. Increased resting activity was indicated by a higher LF/HF ratio compared to controls (1.7 ± 1.23 vs 0.9 ± 0.75, p = 0.002); decreased reactivity by a greater BP fall during valsalva (-19 ± 12 vs -8 ± 10, p < 0.001), and a smaller initial diastolic BP increase during tilt (7% vs 14%, p = 0.032). Orthostatic intolerance was significantly more prevalent in EDS-HT than controls (74% vs 34%) and was most frequently expressed as postural orthostatic tachycardia. Lowered QSART responses suggest that sympathetic neurogenic dysfunction is common in patients (p < 0.013), which may explain the dysautonomia in EDS-HT. Further, connective tissue laxity and vasoactive medication use were identified as important factors in aggravating dysautonomia (p < 0.035). Conclusion: Dysautonomia consisting of cardiovascular and sudomotor dysfunction is present in EDS-HT. Neuropathy, connective tissue laxity, and vasoactive medication probably play a role in its development. © 2014 Elsevier Inc., SCOPUS: ar.j, info:eu-repo/semantics/published

Rett syndrome (RTT) is a rare, severe neurodevelopmental disorder, which partly develops in a predictable way, and influences many bodily functions. Regression, i.e. loss of earlier achieved abilities, is one of the clinical criteria for RTT. Research on motor function has to some extent focused on this loss, and less on the possibility to keep, regain or develop abilities. RTT is mainly verified in girls/women, and the prevalence of classic RTT in Sweden for girls born between 1965 and 1976 was 1 in 10.000-12.000. Clinical criteria are used for diagnosis, but since 1999 RTT can be confirmed by a genetic test. As there is no cure so far, development of clinical intervention and management is important, and with good treatment it is possible to improve quality of life. The main aim was to acquire more knowledge about motor development in RTT, both, early development, and development over time. Another aim was to study if there were deviating orthostatic reactions when rising from sitting to standing, and during standing, compared with normally developed, healthy people, matched by sex and age. Clinical experience as well as reports from parents showed that some people with RTT had lost abilities, some had been able to keep abilities, and some had been able to learn new abilities after regression. For good results, the person with RTT had to be motivated, and the intervention jointly planned; it was also important to realize that dyspraxia causes dependence on other people’s initiatives. Information about one person with RTT, collected over several years, showed the possibility to develop in some areas over time and the tendency to deteriorate in other areas. Studying orthostatic reactions when rising to standing, and standing for three minutes, revealed that those with RTT mainly had the same reactions as the healthy controls. The quicker initial drop in systolic blood pressure in people with RTT, when rising, has not been documented earlier. In conclusion, this th

Hintergrund. Untersuchungen bei Patienten mit funktionellen Mutationen des Noradrenalin-Transporter-Gens deuten darauf hin, dass eine verminderte Noradrenalin-Wiederaufnahme zur Pathophysiologie der idiopathischen Orthostatischen Intoleranz beitragen kann. Methoden. In einer doppeltblinden, placebokontrollierten, randomisierten Studie wurden die kardiovaskulären Effekte einer selektiven pharmakologischen Noradrenalin-Wiederaufnahmehemmung (2x 8 mg Reboxetin p.o.) bei gesunden Testpersonen untersucht. In der ersten Teilstudie (n=23) wurden autonome Funktionstests und eine Kipptischuntersuchung durchgeführt. Herzfrequenz, Blutdruck und zerebrale Blutflussgeschwindigkeit wurden dabei kontinuierlich nicht-invasiv gemessen. Herzzeitvolumen und peripherer Widerstand wurden impedanzkardiografisch bestimmt. In einer zweiten Teilstudie (n=10) wurde der Effekt akuter selektiver Noradrenalin-Wiederaufnahmehemmung auf die Sensitivität gegenüber blutdruckwirksamer Pharmaka getestet. Dafür wurden steigende intravenöse Dosen von Phenylephrin, Isoproterenol und Nitroprussid gegeben und die Änderungen von Blutdruck und Herzfrequenz in individuellen Dosis-Wirkungskurven bestimmt. Ergebnisse. Unter Noradrenalin-Wiederaufnahmehemmung waren Herzfrequenz und Blutdruck im Liegen erhöht. Während der Kipptischuntersuchung führte die Noradrenalin-Wiederaufnahmehemmung zu einer deutlich gesteigerten Herzfrequenz (120+/-3 /min vs. 83+/-3 /min unter Placebo, p, Background. Observations in patients with functional mutations of the norepinephrine transporter (NET) gene suggest that impaired norepinephrine uptake may contribute to idiopathic orthostatic intolerance. Methods. In a double-blind, placebo-controlled, and randomized crossover study we investigated the cardiovascular effects of acute selective pharmacological inhibition of the norepinephrine transporter (2x 8mg reboxetine p.o.) on healthy volunteers. Autonomic function test and a graded head-up tilt test were performed (n=23). Heart rate, blood pressure and cerebral blood flow velocity were measured non-invasively and continuously. Cardiac output and peripheral resistance were measured by impedance cardiography. In a smaller subset of volunteers (n=10) we also investigated the effects of acute inhibition of the Norepinephrine transporter on the sensitivity to pressor and depressor agents. Therefore, increasing doses of phenylephrine, isoproterenol, and nitroprusside were administered intravenously and individual dose-response-curves were plotted. Results. Norepinephrine reuptake inhibition increased both, supine heart rate and blood pressure. During head-up tilt, heart rate was profoundly increased with norepinephrine reuptake inhibition (120+/-3 /min vs. 83+/-3 /min with placebo, p