Resistance exercise as a countermeasure to disuse-induced bone loss.

During spaceflight, skeletal unloading results in loss of bone mineral density (BMD). This occurs primarily in the spine and lower body regions. This loss of skeletal mass could prove hazardous to astronauts on flights of long duration. In this study, intense resistance exercise was used to test whether a training regimen would prevent the loss of BMD that accompanies disuse. Nine subjects (5 men, 4 women) participated in a supine maximal resistance exercise training program during 17 wk of horizontal bed rest. These subjects were compared with 18 control subjects (13 men, 5 women) who followed the same bed rest protocol without exercise. Determination of treatment effect was based on measures of BMD, bone metabolism markers, and calcium balance obtained before, during, and after bed rest. Exercisers and controls had significantly (P < 0.05) different means, represented by the respective following percent changes: lumbar spine BMD, +3% vs. -1%; total hip BMD, +1% vs. -3%; calcaneus BMD, +1% vs. -9%; pelvis BMD, -0.5% vs. -3%; total body BMD, 0% vs. -1%; bone-specific alkaline phosphatase, +64% vs. 0%; alkaline phosphatase, +31% vs. +5%; osteocalcin, +43% vs. +10%; 1,25 dihydroxyvitamin D, +12% vs. -15%; parathyroid hormone intact molecule, +18% vs. -25%; and serum and ionized calcium, -1% vs. +1%. The difference in net calcium balance was also significant (+21 mg/day vs. -199 mg/day, exercise vs. control). The gastrocnemius and soleus muscle volumes decreased significantly in the exercise group, but the loss was significantly less than observed in the control group. The results indicate that resistance exercise had a positive treatment effect and thus might be useful as a countermeasure to prevent the deleterious skeletal changes associated with long-duration spaceflight.

Neocytolysis: physiological down-regulator of red-cell mass.

It is usually considered that red-cell mass is controlled by erythropoietin-driven bone marrow red-cell production, and no physiological mechanisms can shorten survival of circulating red cells. In adapting to acute plethora in microgravity, astronauts' red-cell mass falls too rapidly to be explained by diminished red-cell production. Ferrokinetics show no early decline in erythropolesis, but red cells radiolabelled 12 days before launch survive normally. Selective destruction of the youngest circulating red cells-a process we call neocytolysis-is the only plausible explanation. A fall in erythropoietin below a threshold is likely to initiate neocytolysis, probably by influencing surface-adhesion molecules. Recognition of neocytolysis will require re-examination of the pathophysiology and treatment of several blood disorders, including the anaemia of renal disease.

Control of red blood cell mass during spaceflight.

NASA: Data are reviewed from twenty-two astronauts from seven space missions in a study of red blood cell mass. The data show that decreased red cell mass in all astronauts exposed to space for more than nine days, although the actual dynamics of mass changes varies with flight duration. Possible mechanisms for these changes, including alterations in erythropoietin levels, are discussed.^ieng

Blood volume and erythropoiesis in the rat during spaceflight.

A decreased red blood cell mass (RBCM) and plasma volume (PV) have been consistently found in humans after return from spaceflight. Rats flown on the Spacelab Life Sciences-1 mission were studied to assess changes in RBCM, PV, erythropoiesis, and iron economy. The RBCM and PV increased in both ground control and flight animals as expected for growing rats. However on landing day, both the RBCM and PV, when normalized for body mass, were significantly decreased in the spaceflight animals. During an 8-d postflight observation period, iron incorporation into circulating red blood cells was diminished in the flight animals. During the first 4 d postflight, increases in reticulocyte counts were significantly smaller in the flight than the control animals. Fewer erythropoietin-responsive progenitor cells were recovered from the bone marrow of flight animals after landing than control rats. Serum erythropoietin (EPO) levels were the same in both groups. Thus, rats subjected to a 9-d spaceflight had less increase in RBCM than controls and diminished erythropoiesis during an 8-d post-spaceflight observation period. The rat, like humans, appears to require a smaller blood volume in microgravity.

Decreased production of red blood cells in human subjects exposed to microgravity.

The total-body red blood cell mass (RBCM) decreases during the first few days of spaceflight; however, the pathophysiology of "spaceflight anemia" noted on return to earth is poorly understood. In studies before, during, and after a 9-day mission we determined the rates of removal and replacement of RBCs by using chromium 51. The rate and efficiency of RBC production were assessed with iron 59. Serial measurements were made of plasma volume (PV), RBCM, serum ferritin level, and erythropoietin level. PV decreased within hours, resulting in an increased total body hematocrit during the first few days of the mission. Serum erythropoietin level decreased within 24 hours and remained low. Circulating RBCs disappeared at a normal rate during flight, but few new cells replaced those destroyed, resulting in a decrease in RBCM of 11% during the mission. After 22 hours in space, intramedullary formation of cells continued at near preflight levels as measured by erythron iron turnover. The coexistence of new cell formation in the bone marrow and failure of cells to be released into the blood is consistent with ineffective erythropoiesis. Microgravity causes blood located in gravity-dependent spaces to shift to a central volume. We conclude that the initial adaptation is a reduction in PV resulting in plethora. Increase in total body hematocrit causes a decrease in erythropoietin production. RBCM decreases because RBCs destroyed at a normal rate are not replaced.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of microgravity and increased gravity on bone marrow of rats.

Astronauts have a reduction in their red cell mass when exposed to microgravity. This is probably mainly due to a physiological response to decreased energy requirements. Further studies of erythropoiesis were carried out in microgravity on rats flown on Soviet Biosatellite 2044 and in hypergravity by centrifugation at 2G. Studies included: bone marrow cell differential counts, clonal studies of RBC colony formation, and plasma erythropoietin determinations. In the bone marrow of Cosmos flight animals there was a slight increase in granulocytic cells and in centrifuged animals, a slight decrease in the percentage of erythroid cells which led to an increased M:E ratio. The bone marrow cells of flight and centrifuged rats responded to erythropoietin. Cosmos flight animals' cells formed fewer CFU-E than the controls but this was reversed in the centrifuge studies. There were no essential differences in the erythropoietin levels of test groups as compared to control groups.

Methods for repetitive measurements of multiple hematological parameters in individual rats.

Methods have been developed which permit frequent repetitive blood sampling of rats without perturbing physiological parameters of interest. These techniques allow a comprehensive hematological study over several weeks, in individual rats, thus permitting full documentation of selected parameters during growth and development.

Low-temperature urine collection apparatus for laboratory rodents.

An apparatus for the collection of urine at -19 degrees C from unrestrained small laboratory animals was developed. The cooling unit accommodated five rodent metabolism cages for the collection of urine volumes up to 50 ml per collection period. The unit operated continuously for 5--6 weeks with no maintenance other than removal of the urine specimens, cleaning of the cages and collection dishes, and provision of feed and water.

Prolonged weightlessness effect on postflight plasma thyroid hormones.

Blood drawn before and after spaceflight from the nine Skylab astronauts showed a statistically significant increase in mean plasma thyroxine (T-4) of 1.4 microgram/dl and in thyroid-stimulating hormone (TSH) of 4 muU/ml. Concurrent triiodothyronine (T-3) levels decreased 27 ng/dl indicating inhibited conversion of T-4 to T-3. The T-3 decrease is postulated to be a result of the increased cortisol levels noted during and following each mission. These results confirm the thyroidal changes noted after the shorter Apollo flights and show that thyroid hormone levels change during spaceflight.

Postmission plasma volume and red-cell mass changes in the crews of the first two Skylab missions.

Red-cell mass determinations were performed before and after the first two Skylab missions. The data showed a 14% mean decrease in red-cell mass after the 28-day mission and a 12% mean decrease after the 59-day mission. The red-cell mass returned to premission levels more slowly after the shorter (28-day) than after the longer mission. Plasma volume decreases were found after each mission. with the crew from the longer mission showing the greater change (13% vs. 8.4%). Postmission decreases in red-cell mass and plasma volume have been a general finding in crewmen who return from short or long spaceflight.