Search

Space flight factors are known to cause a malfunction in the human immune system and lead to damage to blood vessels. The hemostatic function of endothelium during space missions and its interaction with human immunity has not been determined so far. In this work, we investigated the markers of endothelial activation and damage (plasma concentrations of soluble thrombomodulin fraction (sTM), von Willebrand factor (vWF), highly sensitive C-reactive protein (hs-CRP)), as well as the level of D-dimer and compared them to the immunological parameters characterizing the state of human humoral and cellular immunity. The immune status of long-duration ISS crewmembers was assessed by whole-blood testing, and comprehensive postflight immune assessment included the analysis of leukocyte distribution. Flow cytometry was applied to determine the absolute counts and the percentage of lymphocyte subsets: B cells (CD19 + ), T cells (CD3 + , CD3 + CD4 + , CD3 + CD8 + ), NK cells (CD3 - CD16 + CD56 + , CD11b + CD56 + ), and activated subsets (CD3 + CD25 + and CD3 + HLA-DR + ). The in vitro basal cytokine production was investigated in whole blood cell culture. The cytokines IFN-gamma, IL-1-beta, IL-4, IL-6, IL-10, IL-18, and TNF-alpha were measured in plasma and the 24-h supernatants by a sensitive enzyme-linked immunosorbent assay. A significant increase in the plasma levels of vWF and hs-CRP and a decrease in the concentration of sTM after spaceflights were detected. Divergent changes in the parameters characterizing the state of the immune system were observed. We propose that the changes revealed may lead to an increase in the procoagulant activity of blood plasma, suppression of protein C activation and thrombin inhibition, as well as to an increase in the adhesive-aggregate potential of platelets, especially in case of changes in the rheological characteristics of blood flow during re-adaptation to ground conditions. We also speculate that the immune system might play an important role in vessel damage during long-duration missions., (© 2022. The Author(s).)

The values of 11 diagnostically significant hemostasis system indices in venous blood were determined during the preflight (30-45 days before start) clinical and physiological examination of 39 cosmonauts aged 35 to 54 who were the members of the main and backup crews of missions to the International Space Station in the period from 2007 to 2014. Since most of the cosmonauts performed several flights during this period, and they were repeatedly included in backup crews, each of the cosmonauts underwent preflight examinations one to five times. The reference values were calculated for each of the studied indices. It was'found that the reference ranges for parameters indicative of integral pro-, anticoagulant and fibrinolytic potential were narrowed and close to the boundaries of ranges for the general population,- which indicates that the cosmonauts had relatively decreased procoagulant potential and increased hemostasis regulative.potential. This was probably due to the criteria of selection, physical training status, and emotional status of crew members during the preflight professional activity, when the adaptive changes against the stress-inducing effects occur in the organism. The cosmonauts who underwent strict medical examination may also have some genetic features which provide higher body resistance and more rapid adaptation processes.

In blood serum of 9 volunteers aged 27 to 42, participated in the experiment with 370-day antiorthostatic hypokinesia (-5 degrees), the lipid peroxidation derivates concentration--diene conjugates (DC), malonic dialdehyde (MDA), Schiff bases (SB) as well as antioxidant defense system indices--tocopherol (TP) concentration and total antioxidative activity level (AOA) were measured. The volunteers were divided into two groups subjected to physical training regimes and used prophylactic measures. In both groups the lipoperoxidation processes initial stages depression (by 54-73%) was observed starting from 50th day, thus the lipid peroxidation final product--SB level was decreased (by 50-61%) only to the 230 day and remains approximately at the same level till the end of the experiment. The restorative period was characterized by decreasing (in 1.6-2.3 times) of MDA and SB concentrations. The decrease in lotal AOA during the aftereffect period was detected in all volunteers, and its level was significantly lower physiological norm range. Probably, long-term adaptation to the simulated weightlessness conditions is accompanied by expressed decrease in biological oxidation processes intensity and significant stress effect, as indicates by essential depression of lipid free radical oxidation in the course of the experiment. At the same time the restorative period after 370-day antiorthostatic hypokinesia was characterized by significantly expressed and prolonged readaptation stress progress. It is evidenced by practically twofold decrease in lipoperoxidation processes intensity against significant increase in TP concentration and water-soluble antioxidants functional reserves exhaustion. Lipid peroxidation activation absence in all terms of examination reflects appropriate compensation of studying impact by volunteers.

In this study the effect of factors of hermetic chamber with modified gas medium on the hemostasis system is analyzed in order to estimate and to compare different diving breathing gases. The parameters characterizing pro-, anticoagulant as well as fibrinolytic components of hemostasis were determined using clotting, chromogenic and immunological methods. The applied exposure did not affect the activity and regulatory potential of hemostasis significantly; however, the nitrogen-oxygen and argon-oxygen diving gases have a different effect on the hemostasis functioning, especially in the recovery period.

The paper is devoted to the hemostasis studies in the course of long-term (520 d) isolation in an airtight chamber. Measured parameters included activated partial thromboplastin time (APTT), international normalized ratio (INR), thrombin time (TT); concentrations of fibrinogen (FBG), plasminogen (PG), Willebrand factor (WF), tissue factor pathway inhibitor (TFPI), and tissue plasminogen activator (TPA), thrombomodulin (TM); activities of the coagulation cascade factors (II, V, VII, X, VIII, IX, XI, XII), antithrombin III (ATIII), protein C (PC), C1-inhibitor (C1), α2-antiplasmin (AP), TPA and TFPI. The investigation revealed a diversity of changes in the plasma fibrinogen concentration, slower blood coagulation in the intrinsic pathway and the final stage, and a relative rise in the activities of ATIII and PC-inhibited factors. The rest parameters showed different trends.

In an experiment with 7-d dry immersion for testing the mechanic foot and electrical muscle stimulation procedures of compensating the support load deficiency the following biochemical parameters were studied: activated partial thromboplastin time, prothrombin time, prothrombin index, international normalized ratio, thrombin time (TT), fibrinogen, soluble fibrin-monomer complexes, D-dimer (DD), plasminogen (PG); antithrombin III activity (ATIII), protein C (PC) and alpha2-antiplasmin (AP). Control subjects (immersed w/o stimulation) did not exhibit significant shifts in the hemostasis system: however, they decreased ATIII, PC and PG in the post-experimental period. Mechanic foot stimulation did not have a noteworthy effect on the hemostasis system functioning during immersion, whereas electromyostimulation increased procoagulant and fibrinolytic activity in blood plasma.

In the 520-d chamber experiment within the international project Mars-500 blood samples of 6 male test-subjects of 28 to 39 years of age were analyzed for water-soluble antioxidants: total bilirubin and uric acid; in addition, total antioxidant capacity of blood plasma was determined. Maximal values of these parameters were associated with the most stressful periods of the experiment, i.e. adaptation to the life in isolation and confinement, simulation of the egress onto Martian surface, and change of the diet. On attainment of the homeostatic equilibrium the parameters stabilized on levels slightly lower relative to baseline (pre-isolation) values. Therefore, dynamics of the water-soluble antioxidants reflected adequately the homeostatic reactions to and compensation by organism of the effects of the 520-day life in isolation and confinement.

Within the period of 2000 to 2012 the values of 40 diagnostically significant biochemical indices in venous blood were being determined during the pre-flight clinical and physiological examination of 28 Russian cosmonauts aged 35 to 54, members of main and back-up crews of expeditions to the International Space Station. The above examination was conducted 45-30 days prior to the launch. Taking account of the fact that each of the most of the cosmonauts performed several flights over the mentioned period and they were repeatedly included in back-up crews over and over again, each of cosmonauts participated in pre-flight examinations 1 to 5 times. Reference values were calculated for each of the studied indices. It was found that reference interval boundaries for 15 indices were narrower as compared to the generally accepted ranges. The upper boundaries of activity reference ranges of a number of enzymes, as well as of concentration of some metabolites of energy and plasticity metabolism were raised relative to mean population values. Thus, it was found that Russian cosmonauts being a specific professional team featured inherent reference values which differed from mean population values in a number of blood biochemical indices. It is conditioned by peculiarities of selection, physical training and psychic and emotional status of crew members during a pre-flight period.

Metabolic effects of physical countermeasures against deficient weight-loading were studied in three groups of 21-30 y.o. volunteers for 7-d dry immersion. Blood serum was investigated for 38 biochemical parameters that characterize myocardium, skeletal musculature, hepatobiliary system, kidney, pancreas, GI tract, prostate, and protein-nucleic, carbohydrate, electrolyte and mineral metabolism. Seven-day DI w/o countermeasures (n = 5) increased concentration of conjugated bilirubin, suppressed activities of muscular (creatine phosphokinase MM) and myocardial enzymes (CPK MB, OBDH), and caused an upward trend in cholesterol, its atherogenic LDP fraction and triglycerides. Mechanic sole stimulation (n = 6) intensified, within the physiological norm, erythrocyte hematolysis raising total bilirubin and potassium. Despite the stimulation, activity of muscle and myocardial enzymes made a decrease. Blood creatinine decreased to a less extent than in the immersed group w/o stimulation, however, lipid parameters did not rise. High-frequency stimulation of the lower leg and hip muscles in the course of immersion (n = 5) was noted to heighten the activity of muscle enzymes and potassium level in blood beyond the physiological norm. Change in creatinine did not reach a statistical significance and lipid metabolism parameters were not different from baseline values. Application of these physical methods of counteracting deficiency of weight bearing did not interfere with redistribution of body liquids due to immersion. Values of the parameters under study were mostly within the normal limits throughout the experimental exposure suggesting absence of pathological developments during DI or in consequence of physical stimulation. Therefore, the reactions were obviously of normal adaptive character.

The present paper deals with studying of hemostasis system indices in the course of the experiment with a 105-day isolation in a hermo chamber. The following values were determined: activated partial thromboplastin time, prothrombin time (PT), prothrombin index (PI), international normalized ratio [relationship] (INR), thrombin time, fibrinogen concentration, soluble fibrin-monomer complexes, D-dimer, plasminogen (PG), activity of antithrombin III, protein C, alpha2-antiplasmin. According to the experiment results, isolation is accompanied by PT prolongation (PI decreasing, INR increasing) which conserves up to the 7th day of the aftereffect period, as well as by PG concentration decreasing. Changes are likely to be connected with peculiarities of reduced motion activity conditions, compensatory physical activity influence, protein and lipid metabolism characteristics changing.

The present paper deals with studying ofhemostasis system indices after short-term (10-11 days) space flights as well as in the course of the experiment with a 7-day "dry" immersion. The following values were determined: activated partial thromboplastin time, prothrombin time, prothrombin index, international normalized ratio (INR), thrombin time (TT); fibrinogen, soluble fibrin-monomer complexes, D-dimer, plasminogen (PG) concentration; activity of antithrombin III (ATIII), protein C (PC), alpha2-antiplasmin (AP). In the 1st day after space flights a fibrinogen concentration was increased significantly as well as TT shortening tendency and fibrinolysis activation tendency were observed. There were no significant changes in ATI I11 and PC activities. During the immersion period there were no significant changes in investigated indices, with the exception of AP activity increase in 3rd day of experiment. In readaptation period, however, a decrease in ATIII and PC activities as well as PG concentration was observed. Hemostasis system response features after space flights and during immersion are probably due to different intensity and duration of external factors effects.

Eight volunteered male test-subjects (20-40 y.o.) took part in an experiment with 21-hr bed rest aimed to investigate trends in the hemostasis parameters (activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen, plasminogen, D-dimers, soluble fibrin-monomer complexes (SFMC), as well as antithrombin III (ATIII) and protein C (antiplasmin) activities) after diuretics-induced dehydration followed by intravenous infusion of colloid and crystalloid solutions. It was shown that noncompensible dehydration during bed rest does not lead to noteworthy alterations in the procoagulating component of hemostasis. Intravenous infusion of blood substituting sterofundin (crystalloid) and venofundin (colloid) to the bedrested human subjects accelerated coagulation within the physiological norm. In all series of the experiment ATIII was suppressed and plasminogen content went down causing growth in SFMC. Fibrinogen concentration remained essentially unchanged pointing to the absence of acute reaction of organism to the experimental conditions.

The effect of a single atropine administration on the activities of angiotensin-converting enzyme and carboxypeptidase N taking part in peptides metabolism was studied. Changes in the enzymes activities after administration were evident during at least 72 h. The role of these enzymes in the metabolism of neuropeptides under the effect of atropine was discussed.