[Some clinical outcomes of fractional gamma-irradiation of primates].

The investigation with macaque-rhesus males aged 3 to 5 years was aimed at evaluation of the effects of 2 patterns of fractional gamma-irradiation ending up with an equal effective residual dose of 100 sGy. Irradiation was carried out on gamma-ray unit GOBO-60 with a 137Cs source and certified activity of 72 g-eq. Ra. Rectal temperature, heart rate, blood pressure and body mass were followed up over the period of 9 months. Rate of body mass gain in primates irradiated with the total gamma-dose of 250 cSv was lower as compared to the group that received the total dose of 132 cSv. Repeated irradiation 3 months later elevated the body mass gain and elevated rectal temperature considerably only in the primates that had been initially irradiated at 250 cSV Fractional gamma-irradiation had no effect on HR or BP.

[Evaluation of effectiveness of short-term orthostatic positioning of head-down tilted primates on the liquid body sectors].

Head-down tilting (HDT) of primates is a well-recognized model for studying the hypokinetic syndrome effects on the body functions. Benefits for the body liquids distribution of periodic transition of primates (rhesus macaques) into the vertical position without support loading were evaluated in a 30-d HDT experiment. Brief (30 to 120 minutes long, 4-5 times a week) transition from tilting into the vertical position had no influence on primates' hydration homeostasis and its infrastructure. However, the orthostatic test at the end of the HDT experiment showed a less increase in blood content of the lower extremities as compared with tilted primates that had not been periodically turned up into the vertical position.

[Effects of antiorthostatic hypokinesia on blood levels of interleukine-1beta and interleukine-6 in primates].

Investigations with Macaca mulatta of 4-5 yrs. of age with the body mass of 4.5-6.5 kg showed that 10 days of tilting with the head end at .5 degrees reduced body temperature but not levels of interleukine-1beta and interleukine-6 in blood plasma. On the next days after return of animals to cages IL-6 was found to increase sharply in more than 10 times. On subsequent 4 days both IL -1beta and IL-6 were within the normal range.

[Body fluids ratio and postural stability of head-down tilted apes in the periods of transition into the active vertical position].

It is known that the hypokinetic syndrome and alteration of the hydrostatic component by microgravity distort functioning of various body systems. Prevention of the adverse effects is achieved through implementation of a variety of physical exercises during tilting, and periodic transition into the upright position. The investigation was performed with 11 Macaques (Macaca mulatta) 3 to 5 yrs. of age and 3.2-7.2 kg of weight. Brief (for 30 to 120 min 4 or 5 times a wk.) transition into the active upright position had a positive effect on the body liquids ratio modification in the course of 27-d HDT (-5 degrees). This was concluded from a less pronounced loss in the amount of extracellular liquid and its interstitial component. In addition, another positive result of this manipulation was less, in terms of volume and speed, significant gravity-dependent blood flow toward the lower limbs during 10 minutes of standing test at the end of the experiment as compared with their controls w/o the preventive manipulation.

[Histomorphometry of primate's iliac bones following head-down tilting and "dry" immersion]. / Gistomorfometriia podvzdoshnykh kostei obez'ian posle antiortostaticheskoi gipokinezii i "sukhoi" immersii.

Histomorphometry of the iliac bone in Macaca mulatta males was performed in experiments with 30-d head-down tilting (HDT, n = 6) and 8-10-d "dry" immersion (DI, n = 6). The iliac crest was sampled two weeks before DI or a month prior to HDT, and immediately after completion of the experiments. HDT was shown to provoke osteopenia in the bone spongy manifested by losses in the volume of spongiosa, number of trabeculae, and growth of the space in-between. Osteoids were noted to gain volume and thickness, whereas the osteoclast resorption surface was not altered The iliac spongiosa deviations following DI were qualitatively similar to those after HDT but more marked as evidenced by reduction in such integral parameter as the spongy volume. Analysis of the data and their comparison with iliac bones taken from the space-flown primates suggest that DI can be viewed as another, besides HDT, ground-based model of microgravity effects on the spongy bone. Exposure in DI was less durable and yet caused qualitatively same atrophy of the iliac spongiosa as HDT though a bit more significant.

[Gravity assisted correction of the hypokinetic syndrome in primates]. / Korrektsiia proiavlenii gipokineticheskogo sindroma u obez'ian s pomoshch'iu gravitatsionnykh vozdeistvii.

In two series of experiments aimed at studying the possibility to alleviate the hypokinetic syndrome in primates with centrifuge-produced artificial gravity (AG) one group of animals was immobilized in the head-down position (HDI, -5 degrees) for 28 d and the other was immobilized and also subjected to regular centrifugation (HDI+AG). In the first series, the animals were rotated at 1.2-1.6 g (+Gz) for 30-40 min 5 times/wk and in the second series, at 1.2 g (+Gz) for 30 min 2 or 3 times/wk. AG abolished the HDI-induced locomotion and coordination disturbances within a short timeframe. Besides, it increased the lymphoid activity and erythropoiesis, and limited growth of haematocrit parameters and shifts in protein metabolism during rehabilitation. Centrifugation reduced amounts of extra-cellular fluids and circulating blood in leg muscles, atrophy of both types of muscle fibers, loss of fiber capillaries, and saved aerobic production of muscles. These effects were less deep in the first series. By the criterion of AG tolerance, centrifugation regime in the second series turned to be more favorable. According to these results, AG (+Gz) from 1.2 to 1.6 g can be used as a preventive to the hypokinetic syndrome in macaques (Macaca mulatta) with due precautions against negative cumulative effects of repeated rotation.

[Prevention of the adverse effects of head-down tilting on the infrastructure of body fluids and postural stability of primates by exposure to g-loads]. / Profilaktika neblagopriiatnogo vliianiia antiortostaticheskoi gipokinezii na infrastrukturu zhidkostnykh sred organizma i postural'nuiu ustoichivost' obez'ian s pomoshch'iu gravitatsionnykh vozdeistvii.

Experiments with 24 primates (Macaca mulatta) demonstrated that head-down tilting (-5 degrees) altered their hydration status as was manifested by a significant diminution of the amount of extracellular fluids, the interstitial fraction specifically. Blood circulation in leg muscles reduced almost in half In addition, return of the animals to the orthostatic position at the end of the experiment did not cause so intensive blood redistribution in leg vessels as in the group of tilted but not rotated animals.

[Blood plasma volume dynamics in monkeys during immersion]. / Dinamika ob"ema plazmy u obez'ian v usloviiakh immersii.

Dynamics of blood plasma volume (PV) was studied with indirect methods (hematocrit count, hemoglobin, total protein and high-molecular protein) during 9-d immersion of monkeys Macaca mulatta. The animals were donned in waterproof suits, motor restrained in space seat liners and immersed down to the xiphisternum. Two monkeys were immersed in the bath at one time. The suits were changed every day under ketamine (10 mg/kg of body mass). There were two groups with 12 animals in each. The first group was kept in the bath 3 days and the second--9 days. Prior to the experiment, the animals had been trained to stay in the seat liner put down into the dry bath. It was shown that already two days of exposure to the hydrostatic forces (approximately 15 mm Hg) and absence of negative pressure breathing reduced PV by 18-20% on the average in all animals. Subsequent PV dynamics was individual by character; however, PV deficit persisted during 4 days of immersion in the whole group. In this period, albumin filtration was increased significantly, whereas high-molecular protein filtration was increased to a less degree. During the remaining days in immersion PV regained normal values. Ten days of readaptation (reclined positioning of monkeys brought back into cage) raised VP beyond baseline values. This phenomenon can be attributed to the necessity to provide appropriate venous return and sufficient blood supply of organs and tissues following extension of blood vessels capacity.

[Basic results of the investigation of the effects of antiorthostatic hypokinesia on the functioning of various systems in monkey's organism]. / Osnovnye rezul'taty issledovaniia vliianiia antiortostaticheskoi gipokinezii na funktsionirovanierazlichnykh sistem organizma obez'ian.

Presented are results of comprehensive studies of functioning various body systems of Macaca mulatta after 4 weeks in antiorthostatic hypokinesia (head-down tilting, HDT). HDT deteriorated monkeys' tolerance of +Gz, altered the higher nervous functioning, and brought about serious disorders in coordination and locomotion. It also impacted energy metabolism, reduced hydration of organism, caused various shifts in the neuroendocrine system, circulation and its controls, and protein, carbohydrate and mineral metabolism. HDT resulted in inhibition of the lymphoid activity of structural components of the lymph nodes, changes in the musculoskeletal apparatus of the lower limbs, atrophic developments in the iliac crest spongiosis, and reduction of the oxidative potential of fibers in the crus extensors, and the number of capillaries in a fiber. These observations are ascribed to redistribution of the body fluids, hypokinesia per se and absence of the effects of support. This HDT model can be applied to monkeys for studying processes of the hypokinetic syndrome and developing countermeasures.

Efficacy of periodic centrifugation of primates during 4-week head-down tilt.

Creation of artificial force of gravity (AFG) to counteract the negative consequences of microgravity in manned space missions of extended duration is one of the high-priority problems of space biology and medicine. However, there are a number of especial effects of AFG (namely, structural changes in muscles and bones, and some other system) which need implantation of electrodes and sensors and are possible only with animals. That is why it is of particular interest to make studies with monkeys whose reactions to changed gravity bear much resemblance with human. The purpose of the investigation was development of a protocol of periodic gravity loads as a counter-measure against the hypokinetic syndrome in Macaca mulatta. Two series of experiments were performed. In the series, animals were split into two groups of 6 species each who were motor restrained with the head end tilted downward at 5 degrees (HDT) for 28 days. Monkeys of group-2 were periodically subjected to centrifugation (HDT+G). During the first series of experiments rotation was conducted in the +Gz direction at g-loads from 1.2 to 1.6 units for 30-40 minutes 4-5 times a week. In the second series, g-load was equal to 1.2 units and the animals were rotated 30 min. 2-3 time a week. The criterion of Y-training protocol efficacy was a test +Gz run at 3 units for 30 s. during which functioning of the cardiovascular systems and its controls was evaluated. The test run was performed prior to and after HDT. Following HDT the animals of group HDT+G were more resistant to the test than their counterparts who had not been trained on the centrifuge. Data of the investigation imply that following HDT and HDT+G alike reduced the amount of total bodily fluids (by approximately 5%), the intracellular component (approximately 4%), and plasma volume (by 6-7%). Yet, there are radical differences between the groups in the levels of reduction in extracellular fluids (by 11% and 6.5%, respectively, P<0.05) and the interstitial component (by 11.5% and 6.5, respectively, P<0.05). Prophylactic centrifugation during HDT was also positive to the muscular blood flow in lower extremities.

Oxygen tension in the somatosensory cortex of rhesus monkeys in space.

Oxygen tension (pO2) in the somatosensory cortex of rhesus monkeys was measured polarographically. Immediately after insertion into orbit (the first 40-60 min), the parameter increased significantly and then fell below the baseline. However, at later flight stages pO2 was adequate, indicating that cerebral circulation regulation adapted well to the space environment and that the somatosensory cortex was not exposed to hypoxemia.

Bion 11 mission: primate experiments.

A summary is provided of the major operations required to conduct the wide range of primate experiments on the Bion 11 mission, which flew for 14 days beginning December 24, 1996. Information is given on preflight preparations, including flight candidate selection and training; attachment and implantation of bioinstrumentation; flight and ground experiment designs; onboard life support and test systems; ground and flight health monitoring; flight monkey selection and transport to the launch site; inflight procedures and data collection; postflight examinations and experiments; and assessment of results.

[The use of pharmacological agents for the increase of +Gz tolerance in macaca mulatta]. / Primenenie farmakologicheskikh preparatov dlia povysheniia perenosimosti peregruzok +Gz obez'ianami Macaca mulatta.

Tolerance of rhesus monkeys to increased +Gz loads was studied in relation to the conditions of the blood circulation functioning. In four anaesthetised monkeys, the external carotid arteries were ligated and a biomedical cuff was implanted on the common carotid arteries to measure blood pressure, linear blood velocity, and to register EKG. Blood flow in the carotid artery nearing the zero served as the criterion for termination of rotation with a gradient of 0.01 units/s Each animal was centrifuged 4 times at a week interval: first when intact and then after injection of m-cholinolytic metacine, adrenomimetic metazone and or reopolyglucin which increases the plasma volume. These studies demonstrated that the reflex effect on the heart (elevated CO and increased arterial pressure as a result of moderate tachicardia conditioned by metacine) or vessels (activation of alfa-receptors by metazone) as well as an increase in the volume of intravascular fluids, are almost equally favourable to the maintenance of the central blood volume, and the +Gz-tolerance, i.e. about 35% (delta = 1.62-1.77 units).

[The effect of a two-week anti-orthostatic hypokinesia on the cardiac function and on the latter's regulation in monkeys]. / Vliianie dvukhnedel'noi antiortostaticheskoi gipokinezii na funktsiiu serdtsa i apparat v usloviiakh ego reguliatsii u obezi'ian.

Investigated were the effects of 2-week exposure of four Macaca mulattas to the head-end tilted downward at 10 degrees on contractility of the left myocardium and its controls basing on the data of functional loading tests on the tilting table and at two regimes of centrifugation. The experiment included registration of the left heart pressure, volumetric blood flow in the aorta, and EKG in order to determine stroke volume, maximal isovolumetric pressure, end-systolic and end-diastolic pressures, maximal contraction and relaxation velocities, end-systolic myocardial elasticity, and a constant of the isovolumetric relaxation. As was stated, HDT does not impair contractility of the left myocardium; however, sensitivity of the HR baroreflex control wakens.

Evidence for increased cardiac compliance during exposure to simulated microgravity.

We measured hemodynamic responses during 4 days of head-down tilt (HDT) and during graded lower body negative pressure (LBNP) in invasively instrumented rhesus monkeys to test the hypotheses that exposure to simulated microgravity increases cardiac compliance and that decreased stroke volume, cardiac output, and orthostatic tolerance are associated with reduced left ventricular peak dP/dt. Six monkeys underwent two 4-day (96 h) experimental conditions separated by 9 days of ambulatory activities in a crossover counterbalance design: 1) continuous exposure to 10 degrees HDT and 2) approximately 12-14 h per day of 80 degrees head-up tilt and 10-12 h supine (control condition). Each animal underwent measurements of central venous pressure (CVP), left ventricular and aortic pressures, stroke volume, esophageal pressure (EsP), plasma volume, alpha1- and beta1-adrenergic responsiveness, and tolerance to LBNP. HDT induced a hypovolemic and hypoadrenergic state with reduced LBNP tolerance compared with the control condition. Decreased LBNP tolerance with HDT was associated with reduced stroke volume, cardiac output, and peak dP/dt. Compared with the control condition, a 34% reduction in CVP (P = 0.010) and no change in left ventricular end-diastolic area during HDT was associated with increased ventricular compliance (P = 0.0053). Increased cardiac compliance could not be explained by reduced intrathoracic pressure since EsP was unaltered by HDT. Our data provide the first direct evidence that increased cardiac compliance was associated with headward fluid shifts similar to those induced by exposure to spaceflight and that reduced orthostatic tolerance was associated with lower cardiac contractility.

Effects of 12 days exposure to simulated microgravity on central circulatory hemodynamics in the rhesus monkey.

Central circulatory hemodynamic responses were measured before and during the initial 9 days of a 12-day 10 degrees head-down tilt (HDT) in 4 flight-sized juvenile rhesus monkeys who were surgically instrumented with a variety of intrathoracic catheters and blood flow sensors to assess the effects of simulated microgravity on central circulatory hemodynamics. Each subject underwent measurements of aortic and left ventricular pressures, and aortic flow before and during HDT as well as during a passive head-up postural test before and after HDT. Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure were measured, and dP/dt and left ventricular elastance was calculated from hemodynamic measurements. The postural test consisted of 5 min of supine baseline control followed by 5 minutes of 90 degrees upright tilt (HUT). Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure showed no consistent alterations during HDT. Left ventricular elastance was reduced in all animals throughout HDT, indicating that cardiac compliance was increased. HDT did not consistently alter left ventricular +dP/dt, indicating no change in cardiac contractility. Heart rate during the post-HDT HUT postural test was elevated compared to pre-HDT while post-HDT cardiac output was decreased by 52% as a result of a 54% reduction in stroke volume throughout HUT. Results from this study using an instrumented rhesus monkey suggest that exposure to microgravity may increase ventricular compliance without alternating cardiac contractility. Our project supported the notion that an invasively-instrumented animal model should be viable for use in spaceflight cardiovascular experiments to assess potential changes in myocardial function and cardiac compliance.

[Effects of microgravity on indices of hemodynamics in monkeys during postural tests]. / Vliianie mikrogravitatsii na pokazateli gemodinamiki u obez'ian pri postural'nykh vozdeistviiakh.

Effects of the 6-day flight on board Cosmos 1667 on the dynamics of arterial pressure (AP) and the linear velocity of blood flow in the common carotid artery were studied with modified postural tests in the experiment with Macaca mulatta No. 18933. Initially, the postural test procedure and the method of mitigating the psychoemotional stress due to transition of the tilt-table were tried out on 21 primates. Administration of the functional test in microgravity was found to exert both qualitative and quantitative effects. The last mentioned were registered only in the primates tilted downward and included lowered AP vs. elevated AP in the control, and absence of typical bradycardia.

[Heart functions in monkeys during a 2-week antiorthostatic hypokinesia]. / Funktsii serdtsa u obez'ian vo vremia dvukhnedel'noi antiortostaticheskoi gipokinezii.

Dynamics of the left heart ventricular muscle contractility and compliance was studied in 4 monkeys in the head down position (antiorthostatic hypokinesia) with the body angle 10 during 2 weeks. Functional tests on a tilt table and under two conditions of centrifuge rotation were performed prior to and after the antiorthostatic hypokinesia. No changes in the left heart ventricular muscle contractility was found. However, the sensitivity level of the baroreflex control decreased. Compliance of the left heart myocardial fibre increased in the first hours and days of the antiorthostatic hypokinesia.