Several morphologic changes in the blood vessels of the rabbit medulla oblongata arising under the influence successive exposure to gravitational overloading and hypokinesia]

Morphological changes in blood vessels of the rabbit medulla oblongata were studied after successive effects of maximum-bearing gravitational overloadings of 10 units applied at different directions and hypokinesia of various duration. Blood system of 35 rabbits was injected with Gerota's mass, cleared horizontal sections of the medulla oblongata 120 mkm thick were stained with hematoxylin--eosin and after Van Gieson. The experiments demonstrated various, quantitative and qualitative, changes in the vessel structure of the medulla oblongata, prevalence of one of the factors applied--in one combination and successive application; total resulting effect of overloading and hypokinesia--in the other combination; peculiar morphological changes unusual to any of the two factors--in the third combination. It was also demonstrated that readaptation for 12 weeks resulted in a significant restoration of the blood vessel structure in the rabbit brains preliminarily subjected to a successive effect of hypokinesia for 4 weeks and overloading in cranio-caudal directions.     

Changes of blood volume distribution by postural changes in rats

During a space flight the human body responds to many different gravities. The launching of the rocket, the weightlessness, the re-entry of the spacecraft, and other factors influence the astronaut's body. The fluid shifts and the effect on the cardiovascular system arising from these gravitational changes have been frequently studied in space medicine by using body tilting, lower body negative pressure (LBNP) and centrifugal accelerators. There exist, however, few reports about the changes in whole body blood volume distribution caused by body tilting. These changes can be measured using radioisotopes: scintigraphy using 99mTechnetium-labeled human serum albumin (99mTc-HSA), etc. In humans, however, because the visual field of the scintillation camera is so small, the simultaneous measurement of whole body blood volume distribution cannot be done during body tilting. We therefore used rats, whose whole bodies can be encompassed within the visual field of the camera, and we discussed the changes in blood volume distribution induced by body tilting. We also measured the blood concentrations in each organ by using whole body autoradiography in mice, and discussed the effect of postural changes on some abdominal organs.     

Remote controlled equipment for multiple blood withdrawal in gravitational physiology experiments

Electro-mechanical equipment for multiple blood withdrawal from small experimental animals applied to a centrifuge with maximal 6g gravitational overloading has been developed and tested. The equipment consists of a transmitter and receiver equipped by microcomputers. Active rotor stepping motors are driving four pairs of syringes. It is also possible to measure the instantaneous gravitational force using an accelerometric transducer. This telemetrically regulated blood sampling allows studying selective effects of hypergravity during centrifugation. It can be also used for study of microgravity effects in the animal organism during space flights for the understanding of the mechanism of the changes of the activity of neuroendocrine system and metabolic processes.     

Quantification of focal contacts in osteoblastic cells--effects of intermittent and continuous gravitational stresses

Osteoblast morphology and attachment were studied during parabolic flight and during centrifugation. Cultures of osteosarcoma cells were exposed to gravitational changes and then analyzed for morphological changes and stained using immunofluorescence staining for vinculin. Changes in cell adhesion parameters and focal contact topography are presented and discussed.     

Effect of 3-week suspension on sympathetic vasoconstrictor response in rat

One of the main problems arising after gravitational unloading is an orthostatic intolerance leading to failure in supporting the upright posture and performing natural locomotion. Among a number of causes for the orthostatic intolerance the decreased circulating blood volume, increased venous distention, alterations in microcirculation, loss of muscular tonus, and regulatory disturbances could be mentioned. The later cause has been intensively studied recently. The aim of the present study is to examine the alterations induced by simulated gravitational unloading in the reaction of resistance vessels of isolated hind limb to the sympathetic stimuli in rats.     

Tolerance of snakes to hypergravity

Sensitivity of carotid blood flow to increased gravitational force acting in the head-to-tail direction(+Gz) was studied in diverse species of snakes hypothesized to show adaptive variation of response. Tolerance to increased gravity was measured red as the maximum graded acceleration force at which carotid blood flow ceased and was shown to vary according to gravitational adaptation of species defined by their ecology and behavior. Multiple regression analysis showed that gravitational habitat, but not body length, had a significant effect on Gz tolerance. At the extremes, carotid blood flow decreased in response to increasing G force and approached zero near +1 Gz in aquatic and ground-dwelling species, whereas in climbing species carotid flow was maintained at forces in excess of +2 Gz. Tolerant (arboreal) species were able to withstand hypergravic forces of +2 to +3 Gz for periods up to 1 h without cessation of carotid blood flow or loss of body movement and tongue flicking. Data suggest that the relatively tight skin characteristic of tolerant species provides a natural antigravity suit and is of prime importance in counteracting Gz stress on blood circulation.     

Microcirculatory bed and the structure of the compact substance of the cat tibial diaphysis normally and after multiple exposure to G loads]

Blood bed and structure of the compact substance of the cat tibial diaphysis have been studied at normal conditions and after repeated effect of gravitational overloadings. Hypergravitation produced a noticeable rearrangement in the microcirculatory bed and in histoarchitectonics of the bone compact substance. The date obtained demonstrate that the changes produced depend on the number of parameters participating in the gravitational effect and on the position of the animal in the container, as well as on the time when the animal falls ill after the experiment.     

Changes in ultrastructure and actomyosin complex of cardiomyocytes in experimental hypergravitation

There were studied the cardiomyocyte ultrastructure, contractile function, actomyosin complex composition and property of the rat ventricular myocardium after repeated gravitational overloading and following rest. In the hypergravitation period cardiomyocyte changes carry destructive character or are regenerative processes manifestation. They are comparable with myocardial contractile function state and with displacements in molecular structure of myofibrillar apparatus. At rest conditions the liquidation of cardiomyocytes destructive changes falls behind the normalization of contractile and regulatory cells of physico-chemical characteristics. The possible reasons of this phenomenon are discussed.     

Pulmonary perfusion is more uniform in the prone than in the supine position: scintigraphy in healthy humans.

The main purpose of this study was to find out whether the dominant dorsal lung perfusion while supine changes to a dominant ventral lung perfusion while prone. Regional distribution of pulmonary blood flow was determined in 10 healthy volunteers. The subjects were studied in both prone and supine positions with and without lung distension caused by 10 cmH2O of continuous positive airway pressure (CPAP). Radiolabeled macroaggregates of albumin, rapidly trapped by pulmonary capillaries in proportion to blood flow, were injected intravenously. Tomographic gamma camera examinations (single-photon-emission computed tomography) were performed after injections in the different positions. All data acquisitions were made with the subject in the supine position. CPAP enhanced perfusion differences along the gravitational axis, which was more pronounced in the supine than prone position. Diaphragmatic sections of the lung had a more uniform pulmonary blood flow distribution in the prone than supine position during both normal and CPAP breathing. It was concluded that the dominant dorsal lung perfusion observed when the subjects were supine was not changed into a dominant ventral lung perfusion when the subjects were prone. Lung perfusion was more uniformly distributed in the prone compared with in the supine position, a difference that was more marked during total lung distension (CPAP) than during normal breathing.     

Influence of repetitive Gz acceleration on structural and metabolic profile of m. vastus lateralis in monkeys exposed to 30 day bedrest

It was shown that changes in structural and metabolic indices of extensor muscles of the lower extremities were usually found in man after exposure to space flight or to bed rest. Similar changes were also observed in monkeys, space-flown on "Kosmos" biosatellites. Response to weightlessness and to restraint was found to be different in m. soleus and in m. vastus lateralis. Therefore, it is important to study structural and metabolic changes of m. vastus lateralis fibers under conditions of gravitational unloading in monkeys, who have motor apparatus similar to that of man, and are much more fruitful object of research. It is assumed that artificial gravity can serve as a countermeasure, aimed at diminishing effects of gravitational unloading. We have studied the effect of repeated gravity overloading, created by means of a centrifuge, on structural and metabolic indices of monkey m. vastus lateralis at the background of 30 day head down tilt bed rest (BR).     

Does gravitational pressure of blood hinder flow to the brain of the giraffe?

Vascular pressure consists of the sum of two pressures: (a) pressure developed by the pumping of the ventricles against the resistance of vessels, designated as viscous flow pressure, and (b) pressure caused by gravity, traditionally called hydrostatic, better described as gravitational pressure. In a conduit, both of these pressures must be overcome when a liquid is discharged to a higher level of gravitational potential energy. If a liquid is returned to its original level, gravity neither helps nor hinders flow because of the siphon effect. This circumstance prevails in the circulatory system. Hence, P1-P2 in the Poiseuille equation excludes gravitational pressure between those points. The long neck of the giraffe, therefore, poses no impediment to blood flow in the erect posture. The giraffe has a high aortic pressure. This is not for driving the blood to its head but is for minimizing the gravitational drop of intravascular pressure and collapse of the vessels. The cerebral circulation is protected by the cerebrospinal fluid which undergoes parallel changes in pressure with posture. Other vessels in the head are less protected by connective tissue, surrounding muscles and other structures. The high aortic pressure in the giraffe is probably caused by the high total peripheral resistance of the systemic circuit due to vascular adaptations related to the overall height of the animal.     

Gravitation importance in the evolution of prehypertension

Gravitation plays the important role in a pathogeny of the essential hypertension (EH). Modifications of hydrostatic pressure during body position changes, related to gravitational action, produce the significant hemodynamics shifts. Discordance of the orthostatic hemodynamics reactions with gravitational action can lead to orthostatic hypotension or proceed without any clinical signs during increased hemodynamic respond. Absence of physiological circulatory orthostatic responses, possibly, is very initial sign of EH development. This assumption is confirmed by the outcomes of the prospective studies in whose have been shown that EH more often develops in patients with normal arterial pressure accompanied by circulatory orthostatic disorders. The prehypertension (PH) became the studies subject only after publication of the report 7 of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (7 JNC). Its diagnosis based on blood pressure (BP) measurement. According to the report, the PH is a risk factor of EH development. Peculiarities of life development on the Earth, phylogenetic features of cardiovascular system evolution and physical effects of gravitational action, allow us to advance a hypothesis that the PH is the beginning of EH pathogenesis. One of the diagnostic methods may be the system hemodynamics study at passive head-up tilt.     

Changes in gravity inhibit lymphocyte locomotion through type I collagen

Summary Immunity relies on the circulation of lymphocytes through many different tissues including blood vessels, lymphatic channels, and lymphoid organs. The ability of lymphocytes to traverse the interstitium in both nonlymphoid and lymphoid tissues can be determined in vitro by assaying their capacity to locomote through Type I collagen. In an attempt to characterize potential causes of microgravity-induced immunosuppression, we investigated the effects of simulated microgravity on human lymphocyte function in vitro using a specialized rotating-wall vessel culture system developed at the Johnson Space Center. This very low shear culture system randomizes gravitational vectors and provides an in vitro approximation of microgravity. In the randomized gravity of the rotating-wall vessel culture system, peripheral blood lymphocytes did not locomote through Type I collagen, whereas static cultures supported normal movement. Although cells remained viable during the entire culture period, peripheral blood lymphocytes transferred to unit gravity (static culture) after 6 h in the rotating-wall vessel culture system were slow to recover and locomote into collagen matrix. After 72 h in the rotating-wall vessel culture system and an additional 72 h in static culture, peripheral blood lymphocytes did not recover their ability to locomote. Loss of locomotory activity in rotating-wall vessel cultures appears to be related to changes in the activation state of the lymphocytes and the expression of adhesion molecules. Culture in the rotating-wall vessel system blunted the ability of peripheral blood lymphocytes to respond to polyclonal activation with phytohemagglutinin. Locomotory response remained intact when peripheral blood lymphocytes were activated by anti-CD3 antibody and interleukin-2 prior to introduction into the rotating-wall vessel culture system. Thus, in addition to the systemic stress factors that may affect immunity, isolated lymphocytes respond to gravitational changes by ceasing locomotion through model interstitium. These in vitro investigations suggest that microgravity induces non-stress-related changes in cell function that may be critical to immunity. Preliminary analysis of locomotion in true microgravity revealed a substantial inhibition of cellular movement in Type I collagen. Thus, the rotating-wall vessel culture system provides a model for analyzing the microgravity-induced inhibition of lymphocyte locomotion and the investigation of the mechanisms related to lymphocyte movement.     

Noninvasive beat-to-beat stroke volume computation during acute hydrostatic pressure changes in parabolic flight

A three-element model of the cardiovascular system was used to monitor stroke volume (SV) changes during parabolic flight. Aortic blood flow was estimated from continuous arterial finger pressure and SV computed by integrating simulated aortic flow during each systole. SV was significantly higher in microgravity (microgravity) compared to 1 G whereas in hypergravity (hG), SV was significantly lower. Exponential SV transients were observed after the transitions to and from microgravity and the succeeding or preceeding hG phases. These SV transients present different time constants, which reflect two different mechanisms of cardiovascular adaptation to sudden gravitational changes. These results show that beat-to-beat computation of SV provides noninvasive information on circulatory adaptation to acute hydrostatic pressure changes.     

Contractile properties, transversal stiffness and cytoskeletal protein content in Mongolian gerbils soleus fibers under long-term hindlimb suspension

Structural and functional changes in Mongolian gerbil soleus fibers were analyzed after a 31-day hindlimb suspension. Contractile properties of muscle fibers were studied by means of tensometry; the transversal stiffness of different parts of the contractile apparatus was measured by atomic force microscopy, resting calcium level was estimated by fluorescence microscopy by using Fluo-4-AM; cytoskeletal protein content was determined by western blotting. It was shown that after gravitational unloading the maximal force of contraction and specific tension of fiber were significantly reduced, as well as calcium sensitivity actually lowered. At the same time, the transversal stiffness of Z-disk in the relaxed and activated state was decreased significantly compared to the control group. Desmin content was at the control level, but alpha-actinin-2, main structural protein of Z-disk, became considerably less after a 31-day hindlimb suspension. Besides, resting calcium level remained at control values during the simulated gravitational unloading. The data suggest that Z-disk destruction, as a result of alpha-actinin-2 content reduction, leads to changes in the lattice spacing and decreases contractile properties.     

Relationship between atrial natriuretic peptide (ANP), renin (PRA), aldosterone (PAC), hemodynamic responses to lower body negative pressure (LBNP) and +Gz tolerance

The redistribution of a certain thoracic blood volume to the lower parts of the body and decrease of the venous return of blood to the heart during lower body negative pressure leads to the central hypovolemia and the deactivation of cardiopulmonary and arterial baroreceptors. Many compensatory mechanisms are involved during central hypovolemia, which is also reflected by the changes in the secretion of different vasoactive hormones. Due to this fact the LBNP stimulus is widely used for the investigation of regulatory (compensatory) mechanisms in cardiovascular system providing deeper understanding of orthostatic reaction. Recently several papers were published on application of this experimental model for +Gz acceleration tolerance assessment. The purpose of this study was evaluate the possible dependence between the changes of ANP secretion, renin-angiotensin-aldosterone system activity, the changes of some hemodynamic parameters during the model of gravitational stress i.e. LBNP exposure and +Gz acceleration tolerance.     

Mechanisms of the decrease in human postural stability during prolonged head-down tilt

In 3 identical experiments with head-down bed rest lasting 60, 90, and 120 days and involving 18 volunteers, dynamics of the development of cardiovascular system (C.V.S) deconditioning was studied. A set of radioisotopic research techniques was used. Volumes of hemocirculation, body fluids, and metabolic activity of the bone marrow were investigated. Functions of the central and peripheral hemodynamics were studied. To determine the extent of C.V.S. deconditioning during the baseline period, on days 60, 90, and 120 of hypokinesia and during recovery, an orthostatic test was performed. The degree of gravitational blood shifting in regions (the head, thorax, the abdomen, the lower extremities) was recorded. Critical thresholds of blood shifting in the body were determined. It was established that the blood pooled in the splanchnic region participates in the decrease of central hypovolemia. Because of the insufficient number of observations, this research should be continued. During recovery, the sign of (CVS) deconditioning noted demonstrated a clear tendency to normalization.     

Mechanisms of vascular adaptation to long-term orthostatic gravitational loading

Frequent symptoms and serious complaints related to orthostatic intolerance are among the important reasons for investigating the long-term control mechanisms of blood vessels especially those of veins. Previously we studied perfused and superfused saphenous vein segments from rats maintained in head-up tilt position for two weeks. It was found that passive lumen capacity and acute pressure induced myogenic response of these vessels increased substantially without measurable change in wall thickness. Sympathetic component of the smooth muscle cell membrane potential determined in vivo was also significantly enhanced in this vein, but no such change was seen in the saphenous artery and in the brachial vessels. In a separate study, rarefaction of microvessels was found in the hind limb oxydative muscles after two-week tilting, while muscular water content was unaltered. These results suggest that long-term gravitational loading may induce adaptive rearrangement of the blood vessel functions. The aim of the present study was to quantitate and compare the density of nerve fiber terminals as well as their synaptic vesicle population in the wall of saphenous vein and artery from tilted rats to those obtained from rats which were maintained in horizontal, control position. It was hypothetized that adaptation of blood vessels to long-term gravitational loading might include also a morphological restructuring of the vascular adrenergic innervation.     

Analysis of erythrocyte aggregation mechanism in presence of dextran and magnetic field by ultrasound scattering in blood

Aggregation of erythrocytes is studied as function of time during their sedimentation process under the gravitational field. The method is based on ultrasonic scattering from the various blood samples in presence and absence of inhomogeneous magnetic field (IMF) and dextran 70 (10%). The experimental arrangement is consisting of ultrasonic transmitter and receiver probes placed in mutually perpendicular direction intersecting at the sampling volume of blood located at the centre of the blood column. The temporal kinetic process is represented in terms of histograms of amplitudes and number of scattering fluctuations related to the size and motion of aggregates. The results show that the application of IMF influences the aggregation and sedimentation of erythrocytes. The aggregates thus formed sediment faster than that of control sample. The aggregate formation and their movements in presence of dextran 70 are slower than that of normal blood which may be attributed to the enhanced suspending medium viscosity and their interaction with erythrocytes.