[Developing the methodology of examining the lower limb veins in cosmonauts for the space medicine practice].

The article centres on development of a methodology for evaluating the function of lower limb veins of cosmonauts in microgravity. The whys and wherefores of the choice of occlusive plethysmography equipment and procedure are explained. Much place is given to arguments for the requisite body and limb positioning during venous plethysmography pre launch and on return from space flight. To minimize the gravity effect on venous blood flow, the body should be in the level position and the calf aligned with the hydrodynamically indifferent point. Determining the type of test occlusion, occlusion adjustments, venous parameters of interest, and data processing procedure constitute the methodology.

[Prediction of human orthostatic tolerance by changes in arterial and venous hemodynamics in the microgravity environment].

The authors intentionally present exclusively the results of their recent studies of arterial and venous hemodynamics as predictors of human orthostatic tolerance (OT) during space flight and on return to Earth. There is a sufficient demonstration of the in-flight OT predictability by arterial hemodynamic reactions to LBNP and venous hemodynamic changes in response to the lower extremities occlusion. Three levels of cerebral blood flow deficits in the course of the lower body negative pressure test (LBNP) performed in microgravity were first defined. The authors offer quantitative arguments for the dependence of cerebral flow deficit on the degree of LBNP tolerance degradation. Patterns of arterial hemodynamics during LBNP were used successfully to diagnose the actual orthostatic tolerance and also to follow its trend as flight extended, which attests to the predictability of OT change in an individual cosmonaut on space flight. Occlusion plethysmography of legs revealed three levels of response of the most informative venous parameters (capacity, distensibility and rate of filling) correlating with severity of OT degradation.

[The features of adaptation and disadaptation of the human cardiovascular system in the space flight conditions].

The work was aimed at analysis and generalization of the hemodynamic data collected over 20 years from 26 cosmonauts flown 8 to 438 days aboard orbital stations Salyut 7 and Mir. The paper presents the results of ultrasonic investigations of the heart, arterial and venous peripheral vessels in different parts of human body, and measurements of leg veins capacity with the use of occlusive plethysmograpy. It was shown that in the resting condition such prime hemodynamic parameters as the pumping function of the heart and blood supply of the brain, and integral parameters, i.e. arterial pressure and heat rate, were best "protected" as they demonstrated stability throughout long exposure in microgravity. In the absence of gravitational stimulation, arterial resistance went down in essentially all vascular regions below the heart level; to put it differently, the anti-gravity distribution of the vascular tone was annulled gradually as unneeded in microgravity. Compared with the data about arteries, venous hemodynamics was found to be particularly sensitive considering the early advent and significance of changes. Venous return slowed down, resistance of the lower body vessels declined and capacity of the leg venous net increased. Functional testing with the lower body negative pressure revealed degradation of the gravity-dependent reactions that became more conspicuous as flight duration extended further. Cardiovascular deconditioning showed itself clearly on return to Earth's gravity by decreased g-tolerance during re-entry and orthostatic instability post flight. These investigations provided objective evidence for multifactorial genesis of orthostatic instability during space flight including blood redistribution, altered tone regulation of leg's venous and arterial vessels and hypovolemia.

[Dynamics of human cardiovascular responses in different periods of long-term exposure in weightlessness].

Purpose of the work was to determine trends in the human cardiovascular function at rest and during LBNP in different periods of short- (8-25 d) and long-term (126-438 d) space flights (SF) using the data of USI and leg occlusive plethysmography. Due to blood redistribution and hypovolemia in the first week on SF, the cardiovascular system decreased the left heart filling and output without loss in myocardium contractility, weakened the renal artery resistance, and increased the maximum capacity of leg veins. In 30-40 days, these developments became more pronounced and were followed by a relative stabilization of hemodynamics at rest. Arterial circulation in the brain was stable; however, passive congestion in the region grew as SF duration extended. The most dramatic changes were observed in leg arteries (weakening of resistance) and veins (increase in maximum capacity). Venous changes were more distinct than arterial. Despite the relative stabilization at rest, LBNP showed a decline of the gravity-dependent reactions which was also a function of SF duration. In the first month of SF, the downward trend of femoral arteries vasoconstriction was not detrimental to cerebral circulation. SF extension impacted regulation of the vascular tone and caused cerebral circulation deficiency during LBNP. In several cases, the hemodynamic reaction to LBNP was affected to the extent which could be qualified as a failure to adapt to the orthostatic condition.

[The problem of artificial gravity: the present status and possible approaches].

The author reviews the Russian and international literature on the potentialities of artificial gravity in extended piloted space flights, especially in view of the declared initiatives to set forth on exploration missions in the first part of this century. Physical deconditioning and loss of tolerance to the gravitational loads consistently have their effects on cosmonauts despite the large assortment of in-flight preventive procedures. Effectiveness of artificial gravity generated by the short-arm centrifuge (SAC) has been assessed in experiments simulating the physiological consequences of microgravity by immersion or HDT, and flown aboard the dedicated satellites. It is emphasized that all the data indiscriminately indicate effectiveness of SAC as a preventive and therapeutic instrument alleviating the negative effects of modeled microgravity. Open issues and research objectives are presented.

[Hemodynamic shifts in humans under the conditions of prolonged microgravity and the role of hypovolemia].

Purpose of this work was to elicit the role of hypovolemia in the development of hemodynamic shifts and loss of orthostatic tolerance in humans during prolonged space flights (PSF). Correlation analysis of the data of in-flight ultrasonic investigations of hemodynamics in resting cosmonauts and bio-impedance measurements of body liquids in different periods during PSF pointed out that changes in the left ventricle filling and renal artery resistance (Rren) reflect the degree of hypovolemia with r = 0.95. The dependence of orthostatic tolerance on hypovolemia fell short of this ambiguity. Lower body negative pressure tests (LBNP) performed by 15 cosmonauts in different periods of PSF typically correlated with the body hydration status at r = 0.94; however, several cosmonauts showed a substantial loss of LBNP tolerance despite a moderate hypovolemia. Therefore, we may hypothesize that hypovolemia is a significant yet not the sole factor in orthostatic disorders. Deconditioning, altered control of hemodynamics, decreased vasoconstriction of arterial vessels and increased compliance of the leg veins have an important, in some cases decisive role in degradation of orthostatic tolerance.

[Individual prediction by the analysis of preflight ECG data of cardiac function disorders in cosmonauts during standard deorbit after long-term space flights and in the period of postflight observation].

ECG records of 25 cosmonauts--members of 30 long-term Mir and ISS missions (73- to 197-day long) in the period of 1995-2007 were analyzed. The ECG records were made during medical selection, clinical-physiological investigations (KFO) before launch, insertion and standard descent, and post-flight KFO. No negative trends were discovered in 70% (n=21) of ECG records during insertion and descent of cosmonauts who had not have significant ECG deviations before flight. In 20% of ECG records (n=6) pre-launch individual properties of cardiac rhythm, conduction and end of the ventricular complex became more pronounced in the period of descent persisting after landing. In 10% of ECG records (n=3) the predicted ECG deviations were not found This was the first time when dynamic analysis of ECG records made on the stages of selection and pre-launch training was successful in predicting of 90% (n=27 of 30) of cardiac function deviations during descent. At the start of rehabilitation from long-term missions essentially each of the cosmonauts displayed ECG deviations which were more considerable as compared with the KFO and descent records.

[Peculiar physiological reactions to +Gx loads of nonprofessional members of short-term missions to the ISS].

Physiological reactions to +Gx loads of 10 nonprofessional members of 8 to 12-d. missions to the ISS some of whom had partial health defciency were compared with data about space station MIR cosmonauts (n=10) who participated in flights of similar duration but were qualified as essentially healthy. Age of the ISS visitors varied between 29 and 60 years, whereas the MIR cosmonauts were 31 to 49 years old. Based on analysis of objective information, the ISS visitors were distinguished by much more pronounced sinus tachycardia and tachypnea during insertion and re-entry. There were several instances of pre-launch extrasystole arrhythmias that persisted during insertion and were, as a rule, more serious during re-entry. Also, descent from orbit caused more frequent cardiac rhythm disturbances, polymorphism and severity in these space flyers in comparison with the MIR cosmonauts. Particularly grave ECG deviations were observed in two 60-y.o. crew members. However, all these disturbances were episodic by character. These results suggest that development of individual programs of medical risk mitigation for nonprofessional flyers to the ISS should give regard for the status of cardiac rhythm regulation as re-entry g-loads may affect ECG dramatically. Besides, the analysis highlighted the necessity of more rigorous selection of aged candidates for ISS missions with partial health deficiency

[Effect of prophylactic device "Braslet" on hemodynamic changes during long-term missions to orbital station Mir].

The benefit from occlusive cuffs (prophylactic device Braslet) to human hemodynamics was evaluated in seven cosmonauts on long-term Mir missions using the ultrasonic technique (Echography and Doppler). Braslet had a positive effect on cosmonauts" state of health during the first month of flight. Improvement of cerebral hemodynamics was attested objectively by reduction of venous congestion. However, the device did not produce a noticeable effect on the leg vein expansibility and capacity at the beginning of long-term mission. Starting on flight month 3, cumulation of the Braslet effect on the leg large veins resulted in progressive vein expansion. Regular wearing of the Braslet device produced changes in expansibility, capacity and elasticity of the veins in lower extremities. Extent of these changes was dependent on period of Braslet application and tightness of occlusion. Though the state of leg veins of the cosmonauts who had been favourable to Braslet during mission did not appear changed after landing, still we cannot make the conclusion that the occlusive cuffs do not bring harm if worn continuously, as their delayed effects have not been evaluated and remain unknown.

[Possibility to predict cosmonauts' orthostatic tolerance following short-and long-term space flights].

According to the analysis of the data of active and passive orthostatic tolerance (OST) testing before and after 67 short- (SSF) and 53 long-term (LSF) space flights OST declined in all the cosmonauts regardless of flight length. Active testing on R+1 after SSF (7 to 25 d) and LSF (49 to 438 d) attested OST loss by 33% and 48%, respectively. Full OST recovery following SSF and LSF was observed in a week and 1.5-2 months, respectively. A correlation was established (r = 0.81) between the post-flight OST loss and pre-flight baseline value. Depending on whether the pre-flight OST value was very good, good or satisfactory, its loss on R+1 after LSF can make up 20-30%, 30-50% and 55-65%, respectively. Consequently, data of preflight OST testing can be used for prediction of its decline post normal space flight.

[Prediction of cardiac function deviations (ECG data) in the course of permanent cosmonaut's monitoring starting from selection till return to earth after short-duration space flight].

Analyzed were deviations in cardiac function in 29 cosmonauts with previous aviation and other occupations ranging of 29 to 61 y.o. who made 8- to 30-day space flights (totai number of flights = 34) between 1982 and 2006. The deviations were identified in ECG records collected during clinical selection, clinical physiological examination (CPE) before flight, insertion and deorbit in transport vehicles, and post-flight CPE. Based on the analysis, the cosmonauts were distributed into three groups. The first group (55.2% of the cosmonauts) did not exhibit noticeable shifts and unfavorable trends in ECG at any time of the period of observation. The second group (34.5%) showed some deviations during selection and pre-flight CPE that became more apparent in the period of deorbit and were still present in post-flight ECG records. The third group (10.3%) displayed health-threatening deviations in cardiac function during deorbit. These findings give start to important investigations with the purpose to define permissible medical risks and ensuing establishment and perfection of medical criteria for candidates to cosmonauts with certain health problems.

[Shifts in human venous hemodynamics in long-term space flight].

Veins and venous hemodynamics before, during and after long-term space flights (SF) were evaluated with the ultrasonic (B-scan, Doppler) techniques and occlusion plethysmography. Fifteen cosmonauts were investigated in eight SFs of about 6 months in duration. In three SFs, 30 investigations of the main veins in different parts of the body were fulfilled with participation of 7 cosmonauts. In five SFs, 48 investigations of venous distensibility in legs were fulfilled with occlusion plethysmography with participation of 8 cosmonauts. Femoral veins tended to increase distension throughout SF. Exaggerated leg veins distensibility and compliance was persistently observed during application of occlusion from the early period of SF (wks 1-2) which, in our opinion, extenuates the reduction in LBNP tolerance and post-flight degradation of orthostatic stability. These shifts were growing markedly till months 2-3 of exposure to microgravity and tended to stabilize at the worst (as compared with prelaunch values) level at the end of six-month SFs.

[Correlation of the cosmonauts' physiological reactions to +Gx loads during deorbit with the hemodynamic shifts in the period of short-term microgravity].

Physiological reactions of four cosmonauts to +Gx during the descent after short-term (less than 30 d) space flights were correlated with the hemodynamic shifts developed previously during the LBNP test and occlusive plethysmography in microgravity. The cosmonauts who had exhibited a sharp decrease in cerebral circulation during the in-flight LBNP tests showed signs of deteriorated cerebral blood flow (vertigo, weakness, hyperhydration) at the attempt to assume the vertical posture and to climb out of the landing module. Also, the cosmonauts found to have the arterial and venous tone significantly dropped in microgravity, suffered petechial hemorrhages in the back integument during the exposure to +Gx. These data suggest a correlation between the physiological reactions of cosmonauts to +Gx at the end of short-term space flight and the shifts in hemodynamics earlier in microgravity.

[Rearrangement of the hemodynamic mechanisms of orthostatic tolerance of humans on long-term space missions].

Orthostatic tolerance (OT) was evaluated in 25 cosmonauts using the traditional standing test before and after space fights of about six months in length; 15 cosmonauts of this group were also subjected to ultrasonic investigation during the lower body negative pressure test before, during and after long-term SF. Efficiency of the OT vascular mechanisms was gradually falling and stabilized at the end of six-month SF at a level significantly below pre-flight level. Post-flight OT recovery took longer time as compared with short-term SF suggesting more profound shifts in the vascular control system. Ultrasonic monitoring of blood flow along the aorta, medial cerebral artery and femoral artery enabled more comprehensive and reliable evaluation of the vascular tone and circulation control and appeared more informative than the traditional recording of integral indices, i.e. HR and BP.

[+Gx-tolerance by the Cosmonauts of ISS crews 1, 6-9 and visiting crews 1-7 aboard Soyuz vehicles].

Analysis of +Gx tolerance of 15 members of short-term ISS missions and 9 members of long-term ISS missions aboard the Soyuz vehicles showed good tolerance during insertion and satisfactory during descent provided the use of in-flight countermeasures and anti-g suit Kentaur inside the vehicle. Objective data about the tolerance of off-nominal +Gx (6.26 and 8.1 G) pointed to a more pronounced sinus tachycardia and tachypnea in a ballistic descent following long-duration weightlessness as compared with nominal. Physiological deviations were transient, functional by character. Cardiac arrhythmia was largely observed during return to Earth. Two cosmonauts were found to develop prognostically unfavorable ECG indications during off-nominal descent. Main factors in these deviations could be age (above 45) and existence of some individual specifics of cardiac rhythm regulation. These results emphasize the necessity of more careful screening of candidates older than 45 years, as weightlessness may impact their general condition and tolerance of g-loads during return to Earth.

[Relationship between the hemodynamic disorders in cosmonauts on short-term space flights and orthostatic stability].

Comparative investigation of the hemodynamic responses of cosmonauts at rest, during occlusive leg plethysmography, and LBNP in relatively short (less than a month) space flights were performed to tie up these measurements with post-landing orthostatic stability (OS). The decreased LBNP tolerance in flight that correlated later on with impaired reactions to both active and passive orthostatic testing are attributed, among other reasons, to deficient vasoconstriction of the main arteries and over-extendibility of veins in the lower extremities. Results of ultrasonic investigations of hemodynamics during LBNP tests before and after space flight and data of leg venous extension in SF can and should be used in predicting cosmonaut's orthostatic status post flight.

[An experimental validation of pharmacological agents to arrest the vestibulo-autonomic syndrome (motion sickness)]. / Eksperimental'noe obosnovanie farmakologicheskikh sredtsv kupirovaniia vestibulo-vegetativnogo sindroma (bolezn' dvizheniia).

The results of development and experimental evaluation of the efficiency of pharmacological means of cupping the vestibulo-vegetative syndrome in man are presented. A model and procedure of evaluation of pharmacological cupping of the Vestibulo-vegetative syndrome are developed. The intramuscular injection of the mixture containing ephedrine, promethazine hydrochloride and strychnine (25, 50, and 1 mg, respectively) appeared most effective.

[Effects of centrifugation-related artificial gravity on the human organism. Positive and negative effects]. / Vliianie na organizm cheloveka iskusstvennoi gravitatsii, sozdavaemoi s pomoshch'iu tsentrifugi. Polozhitel'nye i otritsatel'nye éffekty.

Data of investigations of the artificial gravity issues in centrifuge experiments in Russian, USA and Japan over the past 40 years were analyzed. Periodic +Gz centrifugation was used to prevent or eliminate body deconditioning after 3- to 56-d simulated microgravity, and to increase the body functional reserve (orthostatic stability) in ordinary life. Positive effects included prevention of a decline of gravitational stability and reduction or averting the negative effects of simulated microgravity on various physiological systems. Better results can be achieved by combining artificial g-loads with the well-proven methods of combating deconditioning, i.e. physical training on bicycle ergometer and induced hydration. Human tolerance of g-loads on a short-arm centrifuge with a high (100%) gravitational gradient was found no worse than on a mid-arm centrifuge with a lower (20%) gravitational gradient. Negative effects of +Gz on a short-arm centrifuge were revealed and counteracting measures were determined.

[The short-arm centrifuge: history and possible uses in cosmonautics and health care services]. / Tsentrifuga korotkogo radiusa: istoriia i perspektivy ispol'zovaniia v praktike kosmonavtiki i zdravookhraneniia.

The review has the objective to analyze applicability of short-radius centrifuges (SAC) in clinical practice. Attempts to treat with centrifuges were made already in the XVIIIth century by E. Darwin (1794) and then E. Horn (1818). Positive results were reported but without particulars of the therapeutic courses. Interest in this method was rekindled by initiation of investigations of the centrifuge as a means to counteract the negative effects of microgravity during manned flights to space. The all-round studies of SAC powers at the Institute for Biomedical Problems attested its efficiency in prevention and therapy of the human body deconditioning brought on by simulated microgravity (bed rest, water immersion), in the 80s the method was tested on patients affected with leg ischemi, and complicated reparation of bone fractures. Collaboration of IBMP investigators with clinical doctors (1987) and a series of dedicated investigations (2000) favoured the view that SAC can be successfully used to prevent and treat blood supply disturbances in legs.

[The problem of creation of artificial gravity with the use of a short-radius centrifuge for medical support of interplanetary piloted missions]. / Problema sozdaniia iskusstvennoi sily tiazhesti s pomoshch'iu tsentrifugi korotkogo radiusa dlia meditsinskogo obespecheniia mezhplanetnykh pilotiruemykh poletov.

On the evidence of orbital flights, the system of countermeasures against the effects of microgravity does not fully make for deconditioning of a number of human organs and systems and recovery of preflight physical status and working ability of members of long-term missions takes 1.5 to 2 mos. of the post-flight rehabilitation. In order to maintain the physical form, health and performance of crews in future interplanetary missions, we should be ready to offer them a novel countermeasure, i.e. regular sessions of artificial gravity generated by a short-radius centrifuge (SRC) on board vehicles. The articles presents the substantiation and concept of ground-based simulation studies of health benefits from SRC in interplanetary missions. Of primary concern is development of SRC regimens that will put up a strong opposition to microgravity, assure crew safety, and reduce to the minimum time to fulfill the in-flight countermeasure program. Answers to arising questions can be found by consolidation of the expertise and resources of the countries willing to meet this challenge.