Effect of long-term hypokinesia on cardiac/bioelectric activity in healthy men

Bioelectric activity of the heart was measured in 39 healthy men, aged 25 to 45 years, during their exposure to head-down tilt. The first experimental study which continued for 182 days (-4.5 degrees) was performed on 18 test subjects, and the second study which lasted for 120 days (-4.5 degrees) on 21 test subjects. Both studies included controls (15 subjects) and subjects who exercised during head-down tilt (16 subjects). In addition, the second study also included 4 test subjects who took drugs to modify metabolic shifts and 4 test subjects who were in the drugs + exercise regiment. Prolonged hypokinesia led to a heart rate increase, A-V conductance decrease, and repolarization phase (T-wave) changes. Except for heart rate variations, these changes developed beginning with the first weeks of exposure, plateaued during 1.5 to 2 months and then varied in a sinusoidal manner, coinciding with similar changes in blood neurotransmitters and electrolytes. T-wave changes correlated well with K, Mg and Ca variations in blood. Exercises performed during head-down tilt decreased significantly (1.5-2 times) the level of T-depression and accelerated the restoration of ECG parameters during readaptation. Corinfar taken for two weeks had a noticeably beneficial effect on electrophysiological processes of the heart. The above electrophysiological changes that developed in healthy men during prolonged hypokinesia were of functional, reversible character and disappeared within the 2-month recovery period.     

Characteristics of the functional state of the nervous system of middle-aged persons during anti-orthostatic hypokinesia

The functional state of the nervous system and its autonomic compartment was investigated in 15 men, aged 40-52 years, during their 30-day exposure to head-down tilt (-8 degrees). Group 1 consisted of 9 subjects with early manifestations of cerebral atherosclerosis and Group 2 included 6 subjects with cerebral atherosclerosis and arterial hypertension. The control group incorporated 9 healthy volunteers, aged 25-39 years. During adaptation to head-down tilt, middle-aged and young subjects showed consistent changes in the nervous system. In response to perturbation effects, autonomic reactions were inert and autonomic support was excessive. However delayed onset of responses, duration and slow recovery of the parameters examined indicated that mechanisms of autonomic regulation were inadequate. These changes were most distinct in middle-aged subjects, particularly in Group 2 subjects: recovery of the functional state of the nervous system was completed by day 20 in middle-aged subjects and by day 9 in young subjects. The observations have demonstrated that the nervous system of most middle-aged subjects (taking into consideration age-related and atherosclerotic changes) has a sufficiently high level of functional capabilities during medium-duration head-down tilt studies.     

Impedancimetry of the hydration status and body composition of head-down tilted males]

Studies of the hydration status and body composition of 6 normal males was performed before and after 7-d head-down tilt (-8 degrees) with the use of a portable impedance-measuring device. Fluid sectors in the organism tended to proportionally reduce. By the end of the experiment, the total body fluid was found reduced by 6.4 = 0.9%; the intracellular and extracellular volumes fluids were reduced by 6.4 +/- 0.9% and 6.5 +/- 0.9 %, respectively. Body mass changed but little, and not to the same extent in each subject. Lean body mass measured with the device showed a small reduction (2.0 +/- 0.6 %), whereas the fatty body mass grew in all subjects by 14.0 +/- 3.1% on the average. These results lead to the conclusion that during the 7d head-down tilt the hydration status of the human body grew low concurrent with loss in muscular mass and increase in the body fatty mass.     

Lipid metabolic indices in man during head-down tilt hypokinesia and their correction

Twenty one test subjects exposed to head-down tilt for 120 days were subdivided to four groups: Group 1--nine subjects used as controls, Group 2--three bed rested subjects who performed regular exercises, Group 3--four bed rested subjects who were given selected drugs, including Vitamin F-99 that influenced lipid metabolism, and Group 4--four bed rested subjects who performed regular exercises and received Vitamin F-99. At different stages of bed rest and recovery the content of lipoprotein fractions and lipids of different classes in serum was measured by thin-layer chromatography. The concentration of cholesterol in biliary lipids was determined. In Group 1 and 2 subjects bed rest led to a drastic and significant increase of cholesterol esters in blood, a decrease of phospholipids, variations of triglycerides and non-esterified fatty acids, and a lower percentage content of alpha-lipoproteins. The use of Vitamin F-99 produced positive changes in the above parameters of lipid metabolism (it normalized the level of cholesterol and phospholipids). In Group 4 subjects the effect of exercise combined with drugs was most distinct.     

Cardiovascular dynamics during the initial period of head-down tilt

The cardiovascular response to 1 h of 6 degrees head-down tilt was studied in 12 male subjects, ages 30-39 years, to simulate the early effects of weightlessness. Fluid shifts, hemodynamic variables, and indices of myocardial contractility were evaluated by utilizing electrocardiography, systolic time intervals, impedance cardiography, sphygmomanometry, and measurement of calf circumference. Most cardiovascular variables remained stable throughout the initial 30 min of the protocol, even though translocation of fluid from the legs to the thorax commenced immediately with the onset of head-down tilt. In contrast, minutes 30-60 were characterized by reduced stroke volume, cardiac output, mean stroke ejection rate, and Heather Index concomitant with an elevation in mean arterial pressure. Intrathoracic fluid volume continued to increase while leg volume continued to decrease. This latter physiological response suggests intrathoracic sequestration of fluid volume; blood was apparently redistributed to the pulmonary circulation rather than being retained in the great veins.     

Body position of the human during hypokinesia and water-salt metabolism

Two groups of 5 healthy volunteers each were exposed for 7 days to: 1) group 1 to horizontal bed rest and 2) group 2 to head-down tilt at -6 degrees. The purpose of the study was to determine the effect of body position on fluid-electrolyte metabolism and renal function. During the control period (14 days), bed rest and the recovery period the consumption of fluids and mineral substances and their renal excretion were measured. The typical changes in fluid-electrolyte metabolism during head-down tilt developed faster than during horizontal bed rest. The fluid-electrolyte balance became negative in the course of the exposure and returned to normal during the recovery period. The group 2 subjects showed greater body weight losses due to both fluid and muscle mass losses.     

Closing volume of the respiratory airways and total lung capacity during 7-day antiorthostatic hypokinesis

By mass spectrography and pneumotachography structural variations in total lung capacity (TLC) were investigated in 7 test subjects during 7-day head-down tilt at -15 degrees. By the 7th hour of head-down tilt TLC, vital lung capacity (VLC), functional residual capacity (FRC) and residual volume (RV) decreased significantly and closing volume (CV) increased insignificantly. The CV/FRC ratio grew from 0.82 +/- 0.03 to 1.24 +/- 0.08 (P less than 0.01), indicating the closure of respiratory pathways in certain lung structures within the tidal volume. These changes in the TLC structure persisted till day 7 but the CV/FRC ratio fell down to 1.01 +/- 0.07. The above findings can clarify the mechanism responsible for a lower oxygenation of arterial blood in the head-down position. The expiratory closure of the airways within the tidal volume causes regional changes in alveolar ventilation and ventilation-perfusion relations and, consequently, a larger venous admixture and a smaller oxygen saturation of arterial blood.     

Human amino acid metabolism during combined short-term exposure to head-down tilt hypokinesia and ultraviolet irradiation

Changes in the amino acid pool in the plasma of test subjects exposed to short-term head-down tilt combined with ultraviolet irradiation were investigated. Exposure to head-down tilt alone (Group 1 of 3 test subjects) and combined with ultraviolet irradiation (10 sessions) (Groups 2 and 3 of 3 test subjects each) acted as a stress-agent that diminished the amino acid pool. Exposure to 2-hour head-down tilt in combination with 20 UV-irradiations (Groups 2 and 3) increased the amino acid pool as a result of inhibition of anabolic and stimulation of catabolic processes. The amino acid pool did not return to normal within the recovery period allowed.     

Intraocular pressure, retinal vascular, and visual acuity changes during 48 hours of 10 degrees head-down tilt

Intraocular pressures, retinal vascular diameters, and visual acuities of nine men (ages 19-29), were repeatedly measured while the subjects were tilted 10 degrees head-down for 48 h and while they were seated before (baseline), and after the tilt. An immediate increase in intraocular pressure, measured by pneumatonometer (4.7 +/- 0.6 mm Hg, p less than 0.001) was recorded when subjects assumed the head-down position, and diurnal variations in intraocular pressures were observed for the 48 h. The initial and final head-down intraocular pressures were not significantly different (18.9 +/- 1.2 mm Hg vs. 17.9 +/- 1.4 mm Hg, respectively). However, when subjects resumed the sitting position, intraocular pressures fell below the initial sitting values (14.2 +/- 0.9 pre vs. 11.2 +/- 0.5 post, p less than 0.04). Computer image analysis of the retinal vasculature detected a 6% and 2% reduction in the caliber of arteries and veins, respectively, as compared with sitting baseline values. No changes in visual acuity were documented during the 48 h of head-down tilt. Our data suggest that the choroidal blood reservoir increases in volume over 48 h at continuous head-down position with a compensatory decrease in aqueous volume. These findings may explain intraocular pressure changes noted in astronauts during previous space missions and in studies associated with change in body position.     

Fluid shifts in vascular and extravascular spaces during and after simulated weightlessness

To simulate weightlessness in a normal-gravity environment, eight male subjects were tilted 5 degrees head-down for 8 h to determine vascular and extravascular shifts of fluid. Most of the initial loss of leg volume during head-down tilt represented a passive shift of venous blood toward the head. Facial edema, headache, nasal congestion, and a pronounced diuresis were associated with this redistribution of blood volume. As measured by the wick-catheter technique during head-down tilt, interstitial fluid pressure in lower-leg muscle and overlying subcutaneous tissues decreased by 7.4 and 4.4 mmHg, respectively. Interstitial fluid was shifted from the lower legs at a rate of 12 ml X h-1. Dehydration of lower-leg tissues probably resulted from decreased capillary blood pressure within these tissues during tilt. Other transcapillary pressures were unchanged. The abrupt alterations in local blood pressure upon changes in body posture were probably sufficient to explain all shifts of vascular and extravascular fluid. In this regard, countermeasures may be necessary to maintain precapillary-muscle tone during long space flights in order to prevent swelling of lower-leg tissues upon readjustment to Earth's gravity.     

Changes in hematologic indicators in personnel testing during 370-day anti-orthostatic hypokinesia]

This paper presents the results of evaluating blood morphology (counts of red blood cells, hemoglobin, reticulocytes, platelets, leukocytes and their forms), hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin content and concentration, and erythrocyte sedimentation rate (ESR) in 9 test subjects during a 370-day head-down tilt study. It was demonstrated that blood morphology variations in 9 test subjects remained within normal variations throughout the entire period of observation, including the baseline, head-down tilt, and rehabilitation periods. There were the following exceptions. In the baseline period, a single episode of MCV increase and MCH decrease was recorded. In the course of head-down tilt, monocytosis, lymphocytosis, thrombocytopenia, basophilia, and lowered MCH were occasionally observed. MCV was slightly increased during several measurements. As compared to the norm, hematocrit increased or decreased. After exposure, there was a single episode of a decrease of erythrocyte count and hemoglobin, hematocrit, an increase of MCV and basophil count, and three episodes of monocytosis. These blood changes during 370-day head-down tilt should be viewed as a result of a combined effect of adverse factors accompanying hypokinesia, particularly reduced infection resistance.     

Measurement of the temperature of deep-seated tissues in healthy men during hypokinesia

During a head-down tilt (-5 degrees) study, in which 10 healthy male subjects took part, their body temperature variations were investigated. Skin temperature was measured using and electrothermometer with a point sensor-thermistor and core temperature was measured using a radiothermometer at the wavelength 20 cm. The study showed that the distribution profile of core temperature was close to that of skin temperature: the lowest temperatures were characteristic of the limbs and the highest of the chest, stomach and head. During head-down tilt variations in core temperatures were different from those of skin temperature. As a result, the temperature gradient between the skin and core layers increased by bed-rest day 50. In the subjects who regularly exercised during bed rest the gradient grew because their skin temperature fell while in the subjects who did not exercise the gradient increased due to both factors, i.e. skin temperature decrease and core temperature increase.     

Results of a 4-week head-down tilt with and without LBNP countermeasure: I. Volume regulating hormones.

The volume regulating hormones were studied during a 4-week head-down tilt (CNES HDT) in five subjects with and without (controls) lower body negative pressure (LBNP). LBNP was applied 3 times a day for 3 weeks, 4 times a day for 4 d, and 6 times a day for 3 d the last week. In both groups we observed a significant decrease in body weight (3% in controls, 0.8% in LBNP), a significant increase in plasma renin activity and aldosterone (with an amplification of their rhythms), and a significant decrease in norepinephrine with no difference between the two groups. The only major hormonal difference was observed for atrial natriuretic factor (ANF), which decreased significantly in the control group and increased in the LBNP group. These results are compared with the improvement in orthostatic tolerance (OT) after HDT in the LBNP group in the same protocol (17). We conclude that many factors could be involved in the improvement of OT. The results suggest that better conservation of plasma volume in the LBNP group might have prevented a decrease in ANF. Whether ANF plays a role in the regulation of baroreceptor reflex with an improvement in OT is currently unknown.     

Individual characteristics of water-mineral metabolism during 120-day head-down tilt hypokinesia and the effectiveness of prophylactic measures

Sodium balance and circulating plasma, intracellular, extracellular and interstitial fluid volumes were measured in the test subjects exposed for 120 days to head-down tilt at -5 degrees. The large scatter of the above parameters was associated with individual variations and with the use of different countermeasures against demineralization (exercise and drugs-xydiphone and glucamak). The effect of the countermeasures was different both in qualitative and quantitative terms. It appears that the target of their action was different. The best prophylactic effect was seen when exercise and drugs were used in combination. These findings suggest that individual variations of fluid-electrolyte metabolism during prolonged hypokinesia are related to the different capacity of tissues for water and electrolytes.     

Coronary circulation of the healthy man exposed to tilt tests, LBNP, and head-down tilt

The effect of tilt (head-up and head-down) tests, LBNP tests, and 7-d head-down tilt (at -15 degrees) on coronary circulation was investigated in healthy male volunteers. Catheters were implanted into the coronary sinus and brachial artery. The Ganz catheter in the coronary sinus was used to measure volume flow in the area (constant thermodilution), pressure, and to withdraw samples of outflowing blood for biochemical analysis (acid-base equilibrium and oxygenation). Transfer from supine to upright body position, lower body negative pressure (-30 mm Hg for 20 min), as well as 15 degrees head-down (by day 5-6) produced similar changes in the basic parameters of coronary circulation-reduction of blood flow and oxygen consumption, decrease of pressure in the coronary sinus, and increase of coronary resistance. Transfer from head-up to head-down position caused opposite changes of the above parameters. The changes in coronary circulation were adequate for myocardial metabolic requirements since the biochemical composition of the outflowing blood remained essentially constant during the gravitational exposures described.     

Use of the ferrocerone test for measuring iron reserves in different types of daily activities

A test using an iron containing agent, i.e. ferrocerone, was developed to measure iron reserves in the body. After breakfast the subject took a ferrocerone tablet (0.3 g) containing 0.04 g iron. Iron content was measured in 24 hour urine samples with the aid of bathophenanthroline++. Iron excretion was assessed in 24 ambulatory test subjects, aged 18-21 years. Two basic types differing in the excretion rate in different times of the day. After testing the renal excretion rate of the agent in healthy people was 20.8 +/- 0.7 mg. Iron reserves during head-down tilt tests of various duration were estimated in 20 test subjects, 6 of whom participated in a 50-day study (-6 degrees) and 14 in a 120-day study (-4.5 degrees). Iron utilization was highest on readaptation day 13 (in the 50-day study) and on bed rest days 65-75 (in the 120-day study). Increase in iron requirements coincided in time with the period of hemoglobin recovery.     

Morphological study of the myocardium of monkeys after anti-orthostatic hypokinesia

By histological, morphometric and gravimetric methods the hearts of 7 monkeys exposed to head-down tilt at -6 degrees were examined (2 monkeys were exposed to head-down tilt for 7 days and 5 monkeys were exposed to hypokinesia for 7 days and then to head-down tilt for 12 days; 4 additional monkeys were used as controls). During head-down tilt the heart weight increased due to blood pooling in the Thebesian vessels which was in turn associated with blood redistribution and accumulation in the vessels and parenchymal organs of the upper body. During 7- and 12-day head-down tilt myocardiocytes of the papillary muscles of the ventricles were not enlarged, and the number of functioning capillaries in the papillary muscles diminished.     

Changes in leg volume during microgravity simulation.

Little published information exists regarding the magnitude and time course of cephalad fluid shift resulting from microgravity simulations. Six subjects were exposed to 150 min each at horizontal bed rest, 6 degrees head-down tilt, and horizontal water immersion. Fluid shift was estimated by calculating leg volumes from eight serial girth measurements from groin to ankle before, during, and after exposure. Results were compared with data from the first 3 h of spaceflight. By the end of exposure, total leg volume for the six subjects decreased by 2.6 +/- 0.8%, 1.7 +/- 1.2%, and 4.0 +/- 1.6% for horizontal, head-down, and immersion, respectively. Changes had plateaued for horizontal and head-down and had slowed for immersion. Relatively more fluid was lost from the lower leg than the thigh for all three conditions, particularly head-down. During the first 3 h of spaceflight, total leg volume decreased by 8.6%, and relatively more fluid was lost from the thigh than the lower leg. The difference in volume changes in microgravity and simulated microgravity may be caused by the small transverse pressures still present in ground-based simulations and the extremely nonlinear compliance of tissue.     

Effect of 120-day antiorthostatic hypokinesia on gas exchange and pulmonary circulation in humans

Parameters of gas exchange and pulmonary circulation were measured in five healthy test subjects during 120-day head-down tilt test and early recovery. During the first half of the bed rest study CO2 tension in arterial blood increased significantly. During the second half of the study oxygen and carbon dioxide tension decreased significantly. The mechanisms of these changes are discussed.     

Vascular mechanisms of adaptation to head-down tilt body posture

Using occlusion plethysmography and rheography, the state of peripheral circulation of 18 test subjects during 25 exposures to head-down tilt was investigated. The test subjects were subdivided into two groups: nine subjects actively changed their body position by 90 degrees and nine others were passively transferred to the head-down position at an angle of -12 degrees. It was found that regular training facilitated the development of vascular mechanisms which assisted adaptation to the head-down tilt: it decreased the tone of resistance vessels of the arms and legs and that of capacitance vessels of the legs; it increased the tone of cerebral resistance and capacitance vessels. The tone of leg capacitance vessels varied, depending on the type of training: passive tilting increased their compliance and active tilting decreased it. The final result of the tone redistribution in the peripheral vascular bed during training was a smaller increase of head blood content and a smaller fluid outflow from the legs.