No description available.

The response of the circulatory system to gravity and hydrostatic forces has been well studied, for example the hydrostatic indifferent point (the location at which pressure does not change with posture) of the venous system has been established to be an important determinant of orthostatic responses and it has been found to be located near the diaphragm. However, the role of the abdomen has been less researched; for example, it appears that the concept that the abdominal compartment may have its own hydrostatic indifferent point has been overlooked. The goal of the present study was to establish the location of the abdominal hydrostatic indifferent point (HIPab) and to test the hypothesis that binding of the lower abdomen would shift the location of the HIPab cranially. Intra-abdominal pressure was measured using a modified wick needle technique in the supine and upright posture before and after binding of the lower abdomen in 7 anesthetized rats. In the unbound condition, the HIPab was located 5.2 ± 0.3 cm caudal to the xyphoid, meaning the hepatic veins were exposed to relatively large negative interstitial pressures during head-up tilt. Binding of the lower abdomen significantly (p <0.05) shifted the HIPab cranially by 1.7 cm. Thus, the relatively caudal location of the HIPab causes a relatively large hepatic transmural pressure owing to the fall in interstitial pressure during upright posture. The cranial shift of the HIPab by binding of the lower abdomen lessens the fall in hepatic extramural pressure and thereby protects the hepatic veins from distension.

Persons with chronic fatigue syndrome (CFS) often complain of an inability to maintain activity levels and experience a variety of orthostatic symptoms such as dizziness, trembling, nausea, postural hypotension with bradycardia or tachycardia, sweating, palpitations, paleness, and syncope. Orthostatic intolerance (OI) may be defined as an inability to maintain systolic blood pressure (SBP) within 20 mmHg of resting level upon moving from a supine to upright posture. The primary objective of this study is to determine whether men and women with CFS are more susceptible to OI during a 3-stage head-up tilt (HUT) than non CFS, sedentary subjects matched by age, sex, and ethnicity. The secondary objective is to examine whether possible underlying mechanisms may be predictively associated with OI susceptibility in CFS. Possible causes of OI include autonomic nervous system (ANS) dysfunction and altered hematological profile. Thus, specific aims included within this objective are: 1) to determine whether there are differences in resting cardiovascular function {i.e., blood pressure [BP], heart rate [HR], stroke volume [SV], cardiac output [CO], total peripheral resistance [TPR], and contractility [i.e., ejection fraction (EF), fractional shortening (FS), and the velocity of circumferential shortening corrected by HR (VCFc)]}, ANS function {i.e., beta1-, beta2-, and alpha-receptor sensitivities, baroreceptor sensitivity [BRS], and vagal function [i.e., respiratory sinus arrhythmia (RSA), RSA envelope (RSAE), high frequency (HF) spectral component, and HR range]}, and hematological profile [i.e., red blood cell volume (RBCV), plasma volume (PBV), and total blood volume (TBV)] between CFS and non-CFS groups; and 2) to determine whether cardiovascular, ANS, and hematological measures differentially predicted OI during HUT. The results indicate that OI susceptibility does not occur with greater prevalence in persons with CFS than non-CFS sedentary persons. However, power analyses revealed that with a much larger sample size group differences in OI susceptibility would be found. The CFS group was distinguished from the control group only by differences in blood volume measures. There appears to be no substantive group differences in a range of cardiovascular and ANS measures; moreover, none of these measures, including the blood volume measures, accounted for differences in OI susceptibility. Compensatory mechanisms may be present in CFS for the diminished blood volume that could explain the lack of group differences in OI susceptibility. In addition, future research may find some clues relevant to CFS pathophysiology in the assessment of hemodynamic responses during orthostatic challenge in the present subjects.

One of the age-related changes associated with normal aging is the inability to maintain normal blood pressure homeostasis, a common clinical condition known as orthostatic intolerance. There are little data on the effects of strength training in healthy adults and orthostatic intolerance, and only one study on strength training and elderly adults diagnosed with orthostatic intolerance. Therefore, the purpose of the present study was to evaluate the effects of resistance training on the cardiovascular respones of elderly individuals during an orthostatic challenge. Thirteen subjects were assigned to either a resistance (RES; n=7; 66±5 yrs.) or a control (CON; n=6; 71±6 yrs.) group. During the 12-week treatment period, the RES trained 2x/wk, while the CON was asked not to change their normal lifestyles. The resistance training consisted of 3 sets of 8-12 repetitions using 12 machines at approximately 22% to 57% of 1RM. Before and after the training and control period, subjects were tested using a 70 degree head-up tilt. Tilt consisted of 30 minutes of supine rest while heart rate(HR) was recorded every minute and blood pressure (BP) was taken every 5 minutes. After the rest period, subjects were tilted to 70 degrees for 30 minutes unless subjects experienced presyncopal symptoms. During the tilt period, HR and BP were recorded every minute. After the tilt, subjects were placed in a supine position for 15 minutes of recovery, HR was taken every minute, and BP was taken every 5 minutes. A 2X2X8(test X group X time) Repeated Measures Analysis of Variance was used to analyze data. Significance was accepted at p ≤ 0.05. After the 12 weeks of training, the RES significantly increased upper (46±24 to 55±29kg) and lower (62±20 to 80±31kg) body strength while the CON showed no changes. Body composition measurements by DEXA showed lean mass to increase significantly (50.5±12.9 to 52.7±13.1kg) for the RES group, while the CON showed no changes. Of the 13 subjects only 9 subjects completed the pre and post tilt tests. Of the 9 completing both tilt periods, there were no significant differences between groups for any of the dependent measures of HR, systolic blood pressure, diastolic blood pressure and mean arterial pressure. In conclusion, this study demonstrated that a resistance training program was well tolerated and improved strength and lean mass in the RES. However, training did not help these individuals improve cardiovascular responses to an orthostatic challenge.

The potential role of lower limb blood pooling in reducing venous return to the heart during orthostasis and elevated venous pressure is investigated. This study compares lower limb capacitance, microvascular filtration, and peripheral resistance between a group of highly trained endurance athletes and a group of their sedentary peers. Seven endurance trained males were selected between the ages of 23-33 [(29.1 4.1 yr), mean SD]. The subjects weekly cycling mileage ranged from 80 to 150 miles per week with an average of 125 8.5 miles/week. Nine healthy, age-matched sedentary subjects (25.8 4.8 yr.) were selected for the control group, based upon their reporting they had not participated in repeated lower-body or cardiovascular exercise in the months prior to their study. Results show that both subject groups had similar calf venous capacitances, rates of capillary fluid filtration, and local flow shunting (vascular resistance change) in response to venous thigh occlusion and 70 head-up tilt (HUT). The only significant difference found between groups was the cyclist groups smaller rise in heart rate in response to HUT. The findings of this study suggest that cyclists are not predisposed to orthostatic intolerance due to any changes in lower limb function.

No description available.

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 thesis shows that it is possible for some people with RTT to keep abilities, regain abilities, and also learn new abilities after regression. Since those with RTT recovered their blood pressure in the same way as the healthy controls, there is no reason to recommend limitations in standing, though the quicker initial drop in systolic blood pressure should be noted. The deterioration in walking found in our previous studies does not seem to be due to deviation in orthostatic reactions. Individual analysis, as well as good knowledge about the development of the disorder and variation in its expression, is essential. Since many people with RTT live to adulthood, planning for lifelong intervention and care is most important.

Various models of simulated weightlessness and resulting cardiovascular effects have been researched in the last 50 years of space exploration. Examples of such models are the Alter-G (Alt-G) treadmill used for body unweighting and head-up-tilt (HUT) model each providing similar cardiovascular effects, but differing in their stimulation of vestibular centers . Advantages of using the Alt-G include: use of lower body positive pressure (LBPP) to simulate hypogravity, it acts as a countermeasure to alleviate negative cardiovascular effects of standing and provides a constant vestibular stimulus. In addition, the Alt-G shorts themselves may be providing a certain degree of LBPP, acting as a compression garment. Therefore the purpose of this study was to determine the cardiovascular effects of Alt-G shorts and how effective they are as countermeasure to deconditioning effects of space flight. This study tested cardiovascular changes in 12 men and women at 0 and 80 degrees head-up-tilt (HUT0 / HUT80) with and without Alt-G shorts using 5-lead ECG, 10-lead impedance, heart rate, systolic and diastolic blood pressure measurements at finger and arm. The tilt-induced increase in mean heart rate (HR) was significantly smaller when subjects wore the Alt-G shorts. Shorts ended up reducing HR by 2.3 bpm in supine control and by 6.7 bpm at HUT80 (p0.05. Other cardiovascular variables did not show any significant effect from shorts. In conclusion, this study was in line with results from other studies that used compression garments to determine cardiovascular effects of LBPP.

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

L’encéphalomyélite myalgique (EM) est une maladie complexe, multi-systémique et débilitante, dont l’étiologie est inconnue. D’une personne atteinte d’encéphalomyélite myalgique (PAEM) à l’autre, les symptômes varient en fréquence et en sévérité créant ainsi une grande hétérogénéité clinique entre les individus. Un sous-groupe de PAEM vivent des épisodes d’intolérance orthostatique (IO) ou vivent avec une comorbidité de syndrome de tachycardie orthostatique posturale (POTS), deux conditions qui sont mal comprises. Le malaise après-effort (PEM), un des symptômes phare de l’EM, survient après une activité physique ou mentale minimale. Le malaise après-effort entraîne une dégradation générale de l’état de l’individu, peut entraîner une exacerbation des autres symptômes et va durer de plusieurs heures à plusieurs jours. Chez les individus souffrant de POTS ou d’IO, le malaise après-effort peut déclencher des épisodes d’intolérance orthostatique. Le gène SLC6A2 codant pour le transporteur de norépinephrine NET a été identifié comme potentiel mécanisme dans pathophysiologie du POTS, tout comme les protéines impliquées dans la vasodilatation, comme la thrombospondine-1 (TSP-1). Notre laboratoire a identifié un panel de onze microARN (miARN) exprimés différentiellement chez les PAEM. Parmi ceux-ci, le miR-150-5p a comme cible prédite SLC6A2. Notre hypothèse était qu’une plus grande expression du miR-150-5p après un effort ou qu’une chute de thrombospondine-1 pourrait induire une vasodilatation soudaine contribuant aux symptômes d’IO ou de POTS. Nous avons mesuré les niveaux plasmatiques du miR-150-5p et de TSP-1 avant (T0) et après (T90) l’induction du malaise après-effort chez des PAEM avec POTS/IO (n = 20), chez des PAEM sans POTS/IO (n = 117) et chez des témoins sédentaires associés pour le sexe et l’âge (n = 48). Nous avons démontré que les sujets atteints de POTS/IO avaient des niveau plus importants du miR-150-5p et des symptômes plus sévères. Finalement, nous avons également utilisé la veste intelligente Hexoskin (Carré Technologies Inc., Montreal, Qué., Canada) pour suivre un sous-groupe d’individus (n = 10) sur une plus longue période après l’induction du malaise après-effort. Avec cet outil, nous avons pu monitorer les symptômes au quotidien, permettant un meilleur suivi clinique de ces patients. Ce projet de maîtrise a permis une meilleure compréhension de la pathophysiologie de l’EM et de celle du POTS. / Myalgic encephalomyelitis (ME) is a complex chronic disease with debilitating smyptoms and unknown etiology. Symptoms vary in frequency and severity from a person with ME (PwME) to another, thus creating a highly clinically heterogeneous patient population. Some PwME also experience orthostatic intolerance (OI) episodes or live with a comorbidity of postural orthostatic tachycardia syndrome (POTS), two conditions that are not well understood. Post-exertional malaise (PEM) causes patients to experience a worsening of their symptoms following an effort, whether it be physical or mental. PEM can last from a few hours to several days. In PwME with POTS/OI, PEM can trigger orthostatic intolerance episodes. SLC6A2 is a gene coding for the norepinephrine transporter NET. Its contribution to the POTS pathophysiology has been mentioned several times in literature. A biochemical milieu prone to vasodilation was also reported as a contributing element to POTS pathophysiology. Recently, our laboratory published an article identifying a panel of eleven microRNAs (miRNAs) differentially expressed in PwME. Among these miRNAs, miR-150-5p has been predicted to target SLC6A2. Our hypothesis was that higher expression of miR-150-5p following an effort or a decrease in circulating thrombospondin-1 (TSP-1) inducing vasodilation could contribute to POTS/OI symptoms. We measured circulating levels of miR-150-5p and TSP-1 before (T0) and after (T90) PEM induction in PwME (n = 117), PwME with POTS/OI (n = 20) and age and sex matched sedentary controls (n = 48). We demonstrated that PwME with POTS/OI have higher levels of miR-150-5p at both T0 and T90, while also having more severe symptoms. Furthermore, we used the connected vest Hexoskin (Carré Technologies Inc., Montreal, Qué., Canada) to follow a subgroup (n = 10) of patients for a longer period following PEM induction. With this tool, we were able to monitor symptoms on a daily basis, allowing better clinical follow-up. Overall, this project allowed better understanding of ME and POTS’ pathophysiology.