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Biomedical subjects

V I Korolkov

Publications and source records attributed to V I Korolkov.

At least 19 recordsLinked to original sources

Physiological reactions of primates to 9-D immersion and head-down tilt.

Purpose of the investigation was to compare physiological reactions of primates (Macaca mulatta) to microgravity simulated by immersion and head-down tilt (HDT). In immersion experiments, primates in waterproof suits were put into motion-restraining chairs and immersed into water (t=35.4 degrees C) breast-deep for 9 days. In 9-d HDT experiments, prone primates were motor restrained in dedicated tilt beds at -5 degrees. It was found that the CNS functioning was significantly affected, the plasma volume reduced and the marrow erythropoietic function declined. Atrophy developed in leg muscles on a backdrop of iliopectineal spongy osteopenia. Loss in hydration, inhibition of erythropoietic hemopoiesis and iliopectineal spongy osteopenia were more pronounced following immersion than HDT.

Adaptation, Physiological↗

Hemopoiesis in bone marrow of monkeys after spaceflight.

In six rhesus monkeys flown on Bion 9, 10, and 11, peripheral blood and bone marrow were examined. After the Bion 11 flight, two ground control experiments were performed at R+17 and R+45. The real flight caused changes that were not seen after the control experiments: decreases in hemoglobin, hematocrit, and reticulocytes. During the readaptation period, those parameters returned to normal due to stimulated erythropoiesis and myelopoiesis.

Animals↗

Metabolic parameters of Bion 11 monkeys.

Biochemical parameters of protein, carbohydrate, and fluid-electrolyte metabolism were measured in the blood of Bion 11 rhesus monkeys. The 14-day flight induced changes in total protein, BUN, and calcium, which were also seen in humans during long-duration space missions. It was concluded that protein and calcium metabolism changed while carbohydrate metabolism remained unaltered.

Adaptation, Physiological↗

Energy metabolism of Macaca mulatta during spaceflight.

The mean daily energy expenditure rates of two rhesus monkeys (Macaca mulatta) were determined during spaceflight on the joint U.S./Russian Bion 11 mission by the doubly labeled water (DLW, 2H218O) method. Control values were obtained from two studies performed under flight-like conditions (n = 4). The mean inflight energy expenditure for the two Bion 11 monkeys was 81.3 kcal/kg/day, which was higher than that seen previously. The average energy expenditure (77.6 +/- 4.4 kcal/kg/day) for the four ground control monkeys was slightly lower than had been measured previously.

Animals↗

Bion 11 science objectives and results.

The results from the Bion 11 mission were the most comprehensive set of data ever collected on primate physiology and behavior before, during, and after spaceflight. An international team of scientists representing neuromuscular and behavioral, neurosensory, regulatory, and bone physiology disciplines conducted a wide range of studies, which are briefly summarized herein. New insights were obtained, which can be expected to lead to new, efficient countermeasures for space-related changes, thereby facilitating long-duration human space voyages and providing additional assurance of human health and performance. These data will likely benefit medical areas on Earth that have overlap with challenges in space biology and medicine.

Adaptation, Physiological↗

Bion 11 mission hardware.

The mission hardware provided for Bion 11 shared primate experiments included the launch vehicle, biosatellite, spaceflight operational systems, spacecraft recovery systems, life support systems, bioinstrumentation, and data collection systems. Under the unique Russia/US bilateral contract, the sides worked together to ensure the reliability and quality of hardware supporting the primate experiments. Parameters recorded inflight covered biophysical, biochemical, biopotential, environmental, and system operational status.

Animals↗

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.

Adaptation, Physiological↗

Muscle derived serum enzyme accumulation after +Gz acceleration test in Rhesus monkeys exposed to bed rest.

It is known that several hours of intensive muscle tension result in accumulation of muscle derived enzymes and structural proteins (see review by Clarkson, 1997). We have assumed that, firstly, acute exposure to hypergravity may induce accumulation of serum creatine phosphokinase (CPK), and, secondly, level of that accumulation may be considerably altered after long term hypokinesia.

Animals↗

Dynorphin A(6-12) analogs suppress thermal edema.

Dynorphin A (Dyn A) is a 17-residue opioid peptide derived from prodynorphin precursors found in mammalian tissues. Removal of Tyr1 from Dyn A produces a peptide that is more potent than Dyn A in attenuating the acute phase of the inflammatory response, as measured by inhibition of heat-induced edema in the anesthetized rat's paw (exposure to 58 degrees C water for 1 min). Dyn A(2-17), however, no longer interacts with opioid receptors. It was postulated that the non-opioid anti-inflammatory actions of Dyn A(2-17) may reside in Dyn A(6-12); that is, Arg-Arg-Ile-Arg-Pro-Lys-Leu. here we report on the activities of Dyn A(6-12) analogs modified by substitutions on the N terminus, by single N-methyl substitution and by single replacement of residues by alanine. The results indicated that the minimal sequence required for an anti-edema ED50 of <1.0 micromol/kg i.v. was anisoyl-Arg6-Arg7-Xaa8-Arg9-Pro10)-Xaa11-+ ++Xaa12-NH2. A prototype, p-anisoyl-[D-Leu12] Dyn A(6-12)-NH2, with an ED50 of 0.20 micromol/kg i.v. compared to an ED50 of 0.08 micromol/kg i.v. for Dyn A(2-17), was selected for further tests of biological activity. This analog, like Dyn A(2-17), lowered blood pressure in anesthetized rats. In a model of neurogenic inflammation, produced by antidromic stimulation of the vagus in the anesthetized rat, p-anisoyl-[D-Leu12] Dyn A(6-12)-NH2, 0.23 micromol/kg i.v., attenuated the negativity of tracheal tissue interstitial pressure (Pif), which normally develops after nerve stimulation. Modulation of interstitial pressure may be the mechanistic basis for the anti-edema properties of these Dyn A(6-12) analogs.

Animals↗

Energy expenditure in rhesus monkeys (Macaca mulatta) during spaceflight using doubly labeled water (2H2(18)O).

The mean daily energy expenditure rates of three rhesus monkeys (Macaca mulatta) were determined during spaceflight on the joint US-Russian Cosmos 2044 and 2229 missions by the doubly labeled water (2H2(18)O) method. In-flight values were compared with ground data obtained from seven measurements taken from six chair-adapted control monkeys. The mean energy expenditure for the ground control determinations was 94.5 +/- 6.4 kcal.kg-1.day-1 (n = 6). The mean in-flight energy expenditure, 55.1 +/- 8.0 kcal.kg-1.day-1 (n = 3), was significantly less than the mean ground control value (P < 0.05). These data suggest that energy expenditure in restrained rhesus monkeys is significantly reduced during spaceflight.

Animals↗

Study of physiological effects of weightlessness and artificial gravity in the flight of the biosatellite Cosmos-936.

In the 18.5-day flight of the Soviet biosatellite Cosmos-936 (3-22, August 1977) com-parative investigations of the physiological effects of prolonged weightlessness (20 rats) and artificial gravity of 1 g (10 rats) were carried out. Throughout the flight artificial gravity was generated by means of animal rotation in two centrifuges with a radius of 320mm. Postflight examination of animals and treatment of the flight data were performed by Soviet scientists in collaboration with the specialists from Bulgaria, Czechoslovakia, the German Democratic Republic, Hungary, Poland, Rumania, France and the U.S.A. During the flight the total motor activity of the weightless rats was higher and their body temperature was lower than those of the centrifuged animals. Postflight examination of the weightless rats showed a greater percentage of errors during maze an increase in water intake and a decrease in diuresis; a fall of the resistance of peripheral red cells; an increase in the conditionally pathogenic microflora in the mouth; a decrease of oxygen consumption, carbon dioxide production and energy expenditures; a drop in the static physical endurance; a decline in the capacity to keep balance on the rail; an increase in the latent period of the lifting reflex, etc. The centrifugal animals displayed lesser or no change of the above type. These findings together with the biochemical and morphological data give evidence that during and after flight adaptive processes in the centrifuged rats developed better.

Adaptation, Physiological↗

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.

Adaptation, Physiological↗

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.

Aerospace Medicine↗