Preliminary application of a novel algorithm to monitor changes in pre-flight total peripheral resistance for prediction of post-flight orthostatic intolerance in astronauts

Orthostatic intolerance (OI) is a significant challenge for astronauts after long-duration spaceflight. Depending on flight duration, 20–80% of astronauts suffer from post-flight OI, which is associated with reduced vascular resistance. This paper introduces a novel algorithm for continuously monitoring changes in total peripheral resistance (TPR) by processing the peripheral arterial blood pressure (ABP). To validate, we applied our novel mathematical algorithm to the pre-flight ABP data previously recorded from twelve astronauts ten days before launch. The TPR changes were calculated by our algorithm and compared with the TPR value estimated using cardiac output/heart rate before and after phenylephrine administration. The astronauts in the post-flight presyncopal group had lower pre-flight TPR changes (1.66 times) than those in the non-presyncopal group (2.15 times). The trend in TPR changes calculated with our algorithm agreed with the TPR trend calculated using measured cardiac output in the previous study. Further data collection and algorithm refinement are needed for pre-flight detection of OI and monitoring of continuous TPR by analysis of peripheral arterial blood pressure.     

A new application of LBNP to measure orthostatic tolerance before and after 0-g simulation (water immersion)

Lower body negative pressure (LBNP) remains an important device for the generation of orthostatic stress in the space flight environment as well as a tool to measure inflight and postflight changes in orthostatic response.

These applied levels of LBNP have typically not exceeded 50–60 mm Hg negative pressure. Information is incomplete as to the levels of absolute LBNP orthostatic tolerance, and the factors responsible for their variance. A better definition of the tolerance limits for males and females could be expected to aid the evaluation of lower levels of LBNP.

An LBNP device was built to study absolute orthostatic tolerance; additionally, another LBNP device was constructed to permit orthostatic tolerance testing directly after a controlled water immersion period.

Absolute LBNP orthostatic tolerance patterns are analyzed for a group of males and females (series I). A preliminary statement on the variations of LBNP orthostatic tolerance after limited periods of water immersion and bed rest is also provided (series II).     

Hemodynamic and neurohormonal responses to extreme orthostatic stress in physically fit young adults

Blood pressure stability may be jeopardized in astronauts experiencing orthostatic stress. There is disagreement about cardiovascular and endocrine stress responses that emerge when a critical (presyncopal) state is reached. We studied hemodynamic and neurohormonal changes as induced by an orthostatic stress paradigm (head-up tilt combined with lower body negative pressure) that leads to a syncopal endpoint. From supine control to presyncope, heart rate increased by 78% and thoracic impedance by 12%. There was a 49% fall in stroke volume index, 19% in mean arterial blood pressure, 14% in total peripheral resistance index and 11% in plasma volume. Plasma norepinephrine rose by 107, epinephrine by 491, plasma renin activity by 167, and cortisol by 25%. Hemodynamic and hormonal changes of clearly different magnitude emerge in presyncope as compared to supine rest. Additional studies are warranted to reveal the exact time course of orthostatic changes up to syncopal levels.     

Cardiovascular effects of simulated zero-gravity in humans

Head-down and head-up [correction of heat-up] tilted bedrest (5 degrees) and head out water immersion (HOWI) for 6 hr were compared. Parameters: Cardiac output (rebreathing method), blood pressure (arm cuff), forearm blood flow (venous occlusion plethysmography), total peripheral (TPR), and forearm vascular (FVR) resistances, Hct, Hb, relative plasma volume (PV) changes, and plasma catecholamines (single-isotope assay). During HOWI there was as expected a decrement in TPR, FVR, Mean arterial pressure (MAP, from 100 to 80 mmHg), Hct, and PV, and--as a new finding--catecholamines, which were 30-50% lower compared with both +5 and -5 degrees bedrest. During head down tilt, MAP was elevated (to 100-110 mmHg) and catecholamines did not fall, while TPR and EVR slowly decreased over 6 hr. HOWI is a stronger stimulus than -5 degrees bedrest, probably because HOWI elevates central venous pressure more markedly emptying the peripheral veins, while bedrest permits a distension of veins, which induces an increase in sympathetic nervous activity.     

Does mental arithmetic before head up tilt have an effect on the orthostatic cardiovascular and hormonal responses?

Passive head up tilt (HUT) and mental arithmetic (MA) are commonly used for providing mental and orthostatic challenges, respectively. In animal experiments, even a single exposure to a stressor has been shown to modify the response to subsequent stress stimulus. We investigated whether MA applied before HUT elicits synergistic responses in orthostatic heart rate (HR), cardiac output (CO), heart rate variability and arterial blood pressure. The 15 healthy young males were subjected to two randomized protocols: (a) HUT and (b) HUT preceded by MA, with sessions randomized and ≥2 weeks apart. Beat to beat continuous hemodynamic variables were measured and saliva samples taken for hormonal assay. HUT alone increased HR from 59±7 (baseline) to 80±10 bpm (mean±SD) and mean blood pressure (MBP) from 88±10 to 91±14 mmHg. HUT results after MA were not different from those with HUT alone. The activity of alpha amylase showed differences during the experiments irrespective of the protocols. We conclude that mental challenge does not affect orthostatic cardiovascular responses when applied before; the timing of mental loading seems to be critical if it is intended to alter cardiovascular responses to upright standing.     

The human cardiovascular system during space flight

Purpose of the work is to analyze and to summarize the data of investigations into human hemodynamics performed over 20 years aboard orbital stations Salyut-7 and Mir with participation of 26 cosmonauts on space flights (SF) from 8 to 438 days in duration. The ultrasonic techniques and occlusive plethysmography demonstrated dynamics of changes in the cardiovascular system during SF of various durations. The parameters of general hemodynamics, the pumping function of the heart and arterial circulation in the brain remained stable in all the space flights; however, there were alterations in peripheral circulation associated with blood redistribution and hypovolemie in microgravity. The anti-gravity distribution of the vascular tone decayed gradually as unneeded. The most considerable changes were observed in leg vessels, equally in arteries (decrease in resistance) and veins (increase in maximum capacity). The lower body negative pressure test (LBNP) revealed deterioration of the gravity-dependent reactions that changed for the worse as SF duration extended. The cardiovascular deconditioning showed itself as loss of descent acceleration tolerance and orthostatic instability in the postflight period.     

Spacelab Life Sciences flight experiments: an integrated approach to the study of cardiovascular deconditioning and orthostatic hypotension

The microgravity environment of spaceflight produces rapid cardiovascular changes which are adaptive and appropriate in that setting, but are associated with significant deconditioning and orthostatic hypotension on return to Earth's gravity. The rapidity with which these space flight induced changes appear and disappear provides an ideal model for studying the underlying pathophysiological mechanisms of deconditioning and orthostatic hypotension, regardless of etiology. Since significant deconditioning is seen after flights of very short duration, muscle atrophy due to inactivity plays, at most, a small role. These changes in circulatory control associated with cephalad fluid shifts, rather than inactivity per se, are probably more important factors. In order to test this hypothesis in a systematic way, a multidisciplinary approach which defines and integrates inputs and responses from a wide variety of circulatory sub-systems is required. The cardiovascular experiments selected for Spacelab Life Sciences flights 1 and 2 provide such an approach. Both human and animal models will be utilized. Pre- and post-flight characterization of the payload crew includes determination of maximal exercise capacity (bicycle ergometry), orthostatic tolerance (lower body negative pressure), alpha and beta adrenergic sensitivity (isoproterenol and phenylephrine infusions), baroreflex sensitivity (ECG-gated, stepwise changes in carotid artery transmural pressure with a pneumatic neck collar), and responses to a 24 h period of 5 deg head-down tilt. Measurements of cardiac output (CO2 and C2H2 rebreathing), cardiac chamber dimensions (phased-array 2-dimensional echocardiography), direct central venous pressure, leg volume (Thornton sock), limb blood flow and venous compliance (occlusion plethysmography), blood and plasma volumes, renal plasma flow and glomerular filtration rates, and various hormonal levels including catecholamines and atrial natriuretic factor will also be obtained. The central venous catheter will be inserted immediately pre-launch and monitored with heart rate and blood pressure in-flight until cardiac output, respiratory gas exchange and quantitative 2D echocardiography measurements can be performed. In-flight hemodynamic measurements will be repeated at rest and during submaximal exercise daily and also during maximal exercise midway through the flight to document the timecourse and extent of cardiovascular changes in the payload crew. Parallel studies are planned for the animals. In addition to measurements of right atrial and aortic pressures and cardiac output, a dorsal micro-circulatory chamber will allow determinations of changes in capillary and venular architecture and function in six of the rats. The techniques and findings from many of the SLS-1 and 2 supporting studies have already yielded significant information about circulatory regulation in patients with both hypo- and hypertension. The flight experiments themselves will provide new data to test the validity of both animal and human models currently used for simulating the fluid shifts of a micro-gravity environment. The development of effective countermeasures, not only for short and long duration space travellers, but also for Earth-bound medical patients can then be physiologically based on experimental data rather than anecdote.     

Adaptational changes in the neural control of cardiorespiratory function in a confined environment: the CNEC#3 experiment

The goal of the study was to characterize the changes in neurovegetative control of the circulation, attending the presumed physiological and psychological stress originated by the isolation and confinement typical of the living condition of space stations, as simulated in a ground based unit, using time and frequency domain analysis. As a secondary goal we sought to verify the implementation of real time data acquisition, for off line spectral analisys of R-R interval, systolic arterial pressure (by Finapres) and respiration (by PVF2 piezoelectric sensors).

We addressed the cardiorespiratory and neurovegetative responses to standardized, simple Stressors (active standing, dynamic and static handgrip) on the EXEMSI 92 crew, before, during and after the isolation period.

On average the appropriate excitatory responses (to stand, dynamic and static handgrip) were elicited also in isolation and confinement.

Active standing and small masses muscular exercises are easy to be performed in a confined and isolated environment and provide a valuable tool for investigating the adaptational changes in neural control mechanisms.

The possibility there exists of using this time and frequency domain approach to monitor the level of performance and well being of the space crew in (quasi) real time.     

Cardiovascular reflexes during rest and exercise modified by gravitational stresses.

The hypotheses tested were whether variations in central venous pressure via the low pressure baroreceptors would take over or modify the arterial baroreceptor function, and further to which extent local and "whole body" hydrostatic stresses influence blood flow distribution. We investigated total forearm and skin blood flow (venous occlusion plethysmography and 133-Xe clearance) and cardiac output (rebreathing method) among other parameters. Hypo- and hyper-gravitational stresses were simulated by LBNP, LBPP, water immersion and lowering of the arm. The changes in flow distribution in the arm were ascribed to arterial baroreceptor function and not to low pressure baroreceptor activity. The enhancement of venous return during water immersion increased exercise tolerance during heat stress presumably due both to increased stroke volume and decreased venous pooling. The response to sustained handgrip exercise during LBNP and LBPP was not different from control measurements and the effects explained by arterial baroreceptor function. Application of exercise and local hydrostatic stresses in combination with gravitational stresses represent an interesting model for further study of the mechanisms behind the distribution of cardiac output to the peripheral organs.     

Interaction of mental and orthostatic stressors

We assessed hemodynamic responses induced by orthostatic and mental stressors, using passive head up tilt (HUT) and mental arithmetic (MA), respectively. The 15 healthy males underwent three protocols: (1) HUT alone, (2) MA in supine position and (3) MA+HUT, with sessions randomized and ≥2 weeks apart. In relation to baseline, HUT increased heart rate (HR) (+20.4±7.1 bpm; p<0.001), mean blood pressure (MBP) (+4.7±11.3 mmHg; p<0.05), diastolic blood pressure (DBP) (+6.1±11.6 mmHg; p<0.05) and total peripheral resistance (TPR) (+155±232 dyne*s/cm⁵; p<0.001) but decreased stroke volume (SV) (?33.1±13.4 ml; p<0.001) and cardiac output (CO) (?0.6±1.0 l/min; p<0.01). MA increased HR (+8.0±6.0 bpm; p<0.001), systolic blood pressure (SBP) (+9.0±7.7 mmHg; p<0.001), MBP (+10.0±6.5 mmHg; p<0.001), DBP (+9.5±7.2 mmHg; p<0.001) and CO (+0.6±0.8 l/min; p<0.01). MA+HUT increased HR (+28.8±8.4 bpm; p<0.001), SBP (+4.6±14.3 mmHg; p<0.05), MBP (+11.2±11.6 mmHg; p<0.001), DBP (+13.5±10.1 mmHg; p<0.001) and TPR (+160±199 dyne*s/cm⁵; p<0.001) but SV (?34.5±14.6 ml; p<0.001) decreased. Mental challenge during orthostatic challenge elicited greater increases in heart rate, despite similar reductions in stroke volume such as those during orthostatic stress alone. Overall, cardiac output decreases were less with combinations of mental and orthostatic challenges in comparison to orthostasis alone. This would suggest that carefully chosen mental stressors might affect orthostatic responses of people on standing up. Therefore, additional mental loading could be a useful countermeasure to alleviate the orthostatic responses of persons, particularly in those with histories of dizziness on standing up or on return to earth from the spaceflight environment of microgravity.     

电液伺服型并联式加注机器人运动轨迹跟踪控制

针对电液伺服型并联式加注机器人在实际任务中广泛存在的模型不确定和强外干扰问题，提出一种基于关节有限时间扰动估计(FTDO)的动力学解耦反步鲁棒控制策略。首先，将系统处理为一组受外部扰动关节子系统的集合，进而针对各关节通过设计两个有限时间扰动观测器实现了对关节中匹配与不匹配不确定性的有限时间同步精确估计和补偿。同时，基于系统的动力学解耦模型，通过设计反步鲁棒控制器保证了闭环系统的稳定性。最后，通过Lyapunov方法验证了闭环系统信号的有界性和关节跟踪误差的有限时间渐近收敛特性。试验结果表明，控制器在不同工况下均具有良好的轨迹跟踪性能和关节抗干扰能力，能够满足在实际加注任务中的应用需求 。     

Effects of repeated long duration +2Gz load on man's cardiovascular function

Usefulness of a short-arm human centrifuge is expected when it is used in space as a countermeasure against cardiovascular deconditioning, problem of bone-calcium metabolism, etc. However, nothing is solidly established regarding the most desirable program for artificial G application. Accordingly, this study was designed to analytically evaluate the effects of repeated long duration +Gz load on human cardiovascular function. Recently heart rate spectral analysis has been recognized as a powerful tool for quantitatively evaluating parasympathetic and sympathetic activity separately in human. It is reported that power of the high frequency component (HF-p) is mediated selectively by parasympathetic activity and the power ratio of low to high frequency components(LF/HF) is indicative of cardiac sympathetic activity or cardiac sympathovagal balance. Sequence method is developed to examine spontaneous baroreceptor reflex sensitivity (BRS). We studied cardiovascular control function by using these methods in 9 healthy men before and after 7 days of daily repeated 1hour +2Gz load. When compared with the data of pre-G load period, post-G load period, decrease of HR, increases of HF-p and BRS were statistically significant. SBP, DBP and LF/HF tended to decrease, however, these changes were not statistically significant. This results indicate that repeated +2Gz load increases parasympathetic activity and arterial baroreceptor-cardiac reflex sensitivity. In recent years, many investigators suggest that space flight and head-down bedrest leads to impaired baroreceptor-cardiac reflex responses and decrease of parasympathetic activity, which may contribute to orthostatic intolerance. So our results suggest that daily repeated 1hour +2Gz load would be useful in preventing post-flight orthostatic intolerance.     

Cardiovascular deconditioning during weightlessness simulation and the use of lower body negative pressure as a countermeasure to orthostatic intolerance

The cardiovascular function is one of the main disturbed by weightlessness: it is particularly affected by the astronaut's return to Earth, where symptoms linked to the cardiovascular deconditioning syndrom appear in the following forms: (1) orthostatic intolerance with its risk of syncope: (2) higher submaximal oxygen consumption for an equivalent work load. Lower Body Negative Pressure (LBNP) is intended to stimulate the venous system of the lower limbs; however, the specific effects of periodical LBNP sessions on the orthostatic intolerance have never been studied. With this objective in mind, 5 volunteers took part in two recent antiorthostatic bedrest experiments for 30 days. In the first experiment 3 subjects were submitted to several sessions of LBNP experiment per day and 2 others were controls; in the second experiment the LBNP group of the 1st one became controls and vice-versa. Two orthostatic investigations were performed: (1) 5 days before the bedrest; (2) at the end of the 30 day bedrest period. The results showed: (1) when the subjects were control, a high orthostatic intolerance post bedrest with 3 syncopes and one presyncopal state during the first minutes of the tilt test; (2) when the subjects were submitted to LBNP sessions, no orthostatic intolerance.     

带快速大角度机动附件的卫星在俯仰平面内的运动控制与稳定性研究

研究一类带快速、大角度机动附件的卫星本体的控制与稳定性问题。给出了一类附件作快速、大角度机动时卫星在俯仰平面的动力学方程。采用传统的PD控制,并证明了类闭环系统的一类线性时变系统是指数稳定的,同时证明了在有界激励下,该系统仍能保持稳定。最后仿真验证了分析的正确性。     

再入飞行器自适应最优姿态控制

针对再入飞行器姿态控制问题，应用自适应动态规划（ADP）理论设计了姿态控制器。将再入飞行器的姿态控制建模为非线性系统的最优控制问题，提出单网络积分型强化学习（SNIRL）算法进行求解，该算法简化了积分型强化学习（IRL）算法在迭代计算中的执行-评价双网络结构，只需要采用评价网络估计值函数就可以求得最优控制律，其收敛性得到了理论证明。基于SNIRL算法设计了自适应最优控制器，并证明了闭环系统的稳定性。通过数值仿真校验了SNIRL算法比IRL算法计算效率更高，收敛速度更快，并校验了自适应最优姿态控制器的有效性 。     

Effect of the thigh-cuffs on the carotid artery diameter jugular vein section and facial skin edema: HDT study.

Objective: To evaluate the distal arterial, venous and skin changes in a group using thigh cuffs during daytime and in a control group. Method: Cardiac, arterial, venous parameters were measured by echography and Doppler. Skin thickness was measured by high frequency echography. Results & discussion: Head down position induced plasma volume reduction, increased cerebral resistance, reduced lower limb resistance. The jugular vein increased whereas the femoral and popliteal veins decreased. All these changes were already observed in previous HDT. Common carotid diameter decreased, Front head skin thickness increased and Tibial skin thickness decreased. Eight hours with thigh cuffs increased the cardiac and carotid sizes which is in agreement with the plasma volume increase. Conversely they reduced the cerebral vascular resistance, jugular section and front head edema which may explain the sensation of comfort reported by the subjects. At the lower limb level the thigh cuffs restored the skin thickness to pre-HDT level but enlarged markedly the femoral and popliteal veins. HR, BP, CO, TPR did not change.     

Clinical effects of thigh cuffs during a 7-day 6 degrees head-down bed rest.

Thigh cuffs are used by Russian cosmonauts to limit the fluid shift induced by space flight. A ground simulation using the head-down bed rest (HDBR) model was performed to assess the effects of thigh cuffs on clinical tolerance and orthostatic adaptation. 8 male healthy volunteers (32.4 +/- 1.9 years) participated twice in a 7-day HDBR--one time with thigh cuffs (worn daily from 9 am to 7 pm) (TC) and one time without (WTC). Orthostatic tolerance was assessed by a 10 minute stand test and by a LBNP test (5 min at -15, -30, -45 mmHg) before (BDC-1) and at the end of the HDBR period (R+1). Plasma volume was measured before and at the end of HDBR by the Evans blue dye dilution technique. Thigh cuffs limits headache due to fluid shift, as well as the loss in plasma volume (TC: -5.85 +/- 0.95%; WTC: -9.09 +/- 0.82%, p<0.05). The mean duration of the stand test (R+1) did not differ in the two group (TC 7.1 +/- 1.3 min; WTC 7.0 +/- 1.0 min). The increase in HR and decrease in diastolic blood pressure were slightly but significantly larger without thigh cuffs. Duration of the LBNP tests did not differ with thigh cuffs. Thigh cuffs limit the symptoms due to fluid shift and the loss in plasma volume. They partly reduced the increase in HR during orthostatic stress but had no effect on duration of orthostatic stress tests.     

Sympathetic nervous system and spaceflight

Purpose: Orthostatic stability on Earth is maintained through sympathetic nerve activation sufficient to increase peripheral vascular resistance and defend against reductions of blood pressure. Orthostatic instability in astronauts upon return from space missions has been linked to blunted vascular resistance responses to standing, introducing the possibility that spaceflight alters normal function between sympathetic efferent traffic and vascular reactivity.Methods: We evaluated published results of spaceflight and relevant ground-based microgravity simulations in an effort to determine responses of the sympathetic nervous system and consequences for orthostatic stability.Results: Direct microneurographic recordings from humans in space revealed that sympathetic nerve activity is increased and preserved in the upright posture after return to Earth (STS-90). However, none of the astronauts studied during STS-90 presented with presyncope postflight, leaving unanswered the question of whether postflight orthostatic intolerance is associated with blunted sympathetic nerve responses or inadequate translation into vascular resistance.Conclusions: There is little evidence to support the concept that spaceflight induces fundamental sympathetic neuroplasticity. The available data seem to support the hypothesis that regardless of whether or not sympathetic traffic is altered during flight, astronauts return with reduced blood volumes and consequent heightened baseline sympathetic activity. Because of this, the ability to withstand an orthostatic challenge postflight is directly proportional to an astronaut's maximal sympathetic activation capacity and remaining sympathetic reserve.     

Lower body negative pressure (LBNP) as a countermeasure for long term spaceflight

The article presents the current status of lower body negative pressure (LBNP) as a countermeasure for preventing orthostatic intolerance after space flight or bed rest. Devices discussed include the Chibis vacuum suit, the Anthrorack device, a collapsible device, and an inflatable device. Two bed rest studies examined the effect of LBNP and exercise on orthostatic tolerance; plasma volume; vasopressin, plasma renin activity, and catecholamines; and side effects.     

Nonlinear relative position control of precise formation flying using polynomial eigenstructure assignment

A nonlinear relative position control algorithm is designed for spacecraft precise formation flying. Taking into account the effect of J₂ gravitational perturbations and atmospheric drag, the relative motion dynamic equation of the formation flying is developed in a quasi-linear parameter-varying (QLPV) form without approximation. Base on this QLPV model, polynomial eigenstructure assignment (PEA) is applied to design the controller. The resulting PEA controller is a function of system state and parameters, and produces a closed-loop system with invariant performance over a wide range of conditions. Numerical simulation results show that the performance can fulfill precise formation flying requirements.