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Biomedical subjects

J I Leonard

Publications and source records attributed to J I Leonard.

16 recordsLinked to original sources
PubMed1996

Regulation of body fluid compartments during short-term spaceflight.

The fluid and electrolyte regulation experiment with seven subjects was designed to describe body fluid, renal, and fluid regulatory hormone responses during the Spacelab Life Sciences-1 (9 days) and -2 (14 days) missions. Total body water did not change significantly. Plasma volume (PV; P < 0.05) and extracellular fluid volume (ECFV; P < 0.10) decreased 21 h after launch, remaining below preflight levels until after landing. Fluid intake decreased during weightlessness, and glomerular filtration rate (GFR) increased in the first 2 days and on day 8 (P < 0.05). Urinary antidiuretic hormone (ADH) excretion increased (P < 0.05) and fluid excretion decreased early in flight (P < 0.10). Plasma renin activity (PRA; P < 0.10) and aldosterone (P < 0.05) decreased in the first few hours after launch; PRA increased 1 wk later (P < 0.05). During flight, plasma atrial natriuretic peptide concentrations were consistently lower than preflight means, and urinary cortisol excretion was usually greater than preflight levels. Acceleration at launch and landing probably caused increases in ADH and cortisol excretion, and a shift of fluid from the extracellular to the intracellular compartment would account for reductions in ECFV. Increased permeability of capillary membranes may be the most important mechanism causing spaceflight-induced PV reduction, which is probably maintained by increased GFR and other mechanisms. If the Gauer-Henry reflex operates during spaceflight, it must be completed within the first 21 h of flight and be succeeded by establishment of a reduced PV set point.

Adult↗
PubMed1991

Mathematical modeling of acute and chronic cardiovascular changes during Extended Duration Orbiter (EDO) flights.

The Extended Duration Orbiter (EDO) program aims to extend the capability of the Shuttle orbiter beyond its current 7-10 day limit on mission duration. This goal is to be accomplished in steps, partly due to our limited knowledge of the physiological changes resulting from long-term exposure to weightlessness and their likely influence on critical mission operations involved in EDO flights. Answers to questions related to physiologic adaptation to weightlessness are being actively sought at the present time to help implement the EDO program. In the cardiovascular area, the loss of orthostatic tolerance is a medical concern because of its potential adverse effects on crew performance and safety during reentry and following return to earth. Flight and ground-based physiologic studies are being planned to understand the mechanism and time course of spaceflight-induced orthostatic intolerance and to develop effective countermeasures for improving post-flight cardiovascular performance. Where feasible, these studies are aided by theoretical analyses using mathematical modeling and computer simulation of physiological systems. This paper is concerned with the application of proven models of circulatory and cardiovascular systems in the analysis of chronic cardiovascular changes under weightless conditions.

Cardiovascular Deconditioning↗
PubMed1990

Life sciences issues affecting space exploration.

The U.S. space program is undertaking a serious examination of new initiatives in human space exploration involving permanent colonies on the Moon and an outpost on Mars. Life scientists have major responsibilities to the crew, to assure their health, productivity, and safety throughout the mission and the postflight rehabilitation period; to the mission, to provide a productive working environment; and to the scientific community, to advance knowledge and understanding of human adaptation to the space environment. Critical areas essential to the support of human exploration include protection from the radiation hazards of the space environment, reduced gravity countermeasures, artificial gravity, medical care, life support systems, and behavior, performance, and human factors in an extraterrestrial environment. Developing solutions to these concerns is at the heart of the NASA Life Sciences ground-based and flight research programs. Facilities analogous to planetary outposts are being considered in Antarctica and other remote settings. Closed ecological life support systems will be tested on Earth and Space Station. For short-duration simulations and tests, the Space Shuttle and Spacelab will be used. Space Station Freedom will provide the essential scientific and technological research in areas that require long exposures to reduced gravity conditions. In preparation for Mars missions, research on the Moon will be vital. As the challenges of sustaining humans on space are resolved, advances in fundamental science, medicine and technology will follow.

Adaptation, Physiological↗
PubMed1986

Understanding metabolic alterations in space flight using quantitative models: fluid and energy balance.

This report summarizes many of the results obtained during the Skylab program, on metabolic changes during weightlessness. The examination of the data was conducted following an integrated multi-disciplinary and multi-experimental approach. Emphasis is given on several major aspects of metabolic adaptation to space flight: fluid-electrolyte regulation, mechanisms of hormone disturbances, energy balance and etiology of weight loss. The aim is to obtain a composite picture of the fluid, electrolyte and energy response to weightlessness.

Adaptation, Physiological↗
PubMed1983

Quantitation of tissue loss during prolonged space flight.

An analysis of data from the three Skylab missions was performed to assess the lean body mass (LBM) and fat components of inflight body weight loss. Six methods for determining LBM were employed based on changes in total body water, total body potassium, nitrogen balance, potassium balance, and stereophotometric-body density. Those based solely on body potassium, and potassium and nitrogen balances (when expressed as shifts from preflight control), consistently overestimated LBM loss unless appropriate corrections were made. The average results from the various methods indicated that of a mean inflight total body weight loss of 2.7 +/- 0.3 kg (SD) for all nine crewmembers, more than half (1.5 +/- 0.3 kg) can be attributed to loss of LBM (including 1.1 kg body water), the remainder (1.2 +/- 0.3 kg) being derived from fat stores. The reduction of LBM appeared to be complete after the first month of flight and thereafter was largely independent of mission duration, diet, and exercise.

Adipose Tissue↗
PubMed1982

A systems approach to the physiology of weightlessness.

This paper presents a systems approach to the unraveling of the complex response pattern of the human subjected to the challenge of weightlessness. The major goal of this research is to obtain an understanding of the role that each of the major components of the human system plays following the transition to and from space. The cornerstone of this approach is the utilization of a variety of mathematical models in order to pose and test alternative hypotheses concerned with the adaptation process. An integrated hypothesis for the human physiological response to weightlessness is developed.

Adaptation, Physiological↗
PubMed1981

Dynamic regulation of erythropoiesis: a computer model of general applicability.

A mathematical model for the control of erythropoiesis has been developed based on the balance between oxygen supply and demand at a renal oxygen detector which in turn controls erythropoietin release and red cell production. Tissue oxygen tension is regulated by adjustments of hemoglobin levels resulting from the output of a renal-bone marrow controller. Special consideration given to the determinants of tissue oxygenation included evaluation of the influence of blood flow, capillary diffusion, oxygen uptake, and oxygen-hemoglobin affinity. A theoretical analysis of the overall control system is presented including: a) dynamic and steady-state responses, b) sensitivity analysis to determine the relative importance of parameters and their influence on model behavior, c) properties of the model as a proportional controller, d) analysis of steady-state errors, and e) effectiveness of feedback regulation. Computer simulations of altitude hypoxia, descent from altitude, red cell infusion, and hemolytic anemia demonstrate the validity of the model for general human application.

Anemia, Hemolytic↗
PubMed1981

Interactions of animal and computer models in investigations of the "anemia" of space flight.

Previous studies in mice deprived of water have suggested that these animals, like men in space, show hemoconcentration due to plasma volume reductions, a weight loss greater than that due to fluid loss alone, and suppression of red blood cell production. To more fully understand the mechanisms responsible for the suppressed erythropoiesis in dehydrated mice, a mathematical model for erythropoietic regulation has been adapted to this rodent. Computer simulations suggested several new experimental studies to more fully understand the erythroid response to dehydration. The investigations were directed to determining whether dehydration was accompanied by: a) a shortened red blood cell survival, b) altered sensitivity of the erythropoietin (Ep)-producing mechanism, c) a shortened red blood cell transit time, d) changes in the Ep serum half-life, e) changes in hemoglobin P50, and f) reduced renal blood flow. All parameters except changes in renal blood flow were investigated in vivo and incorporated into, or omitted from, the mathematical simulations as directed by experimental findings. The mathematical model is able to realistically simulate the in vivo erythroid response to dehydration making only one, experimentally-untested, assumption. Computer simulations confirm conclusions drawn from the animal studies that the primary cause of the suppressed erythropoiesis in dehydrated mice is the reduced food intake, with hemoconcentration playing a relatively minor role. The interaction between computer simulations and animal experiments is shown to be a powerful approach for formulating and testing hypotheses, designing new experiments, and achieving a clearer understanding of the factors controlling erythropoiesis.

Anemia↗
PubMed1980

Animal & computer investigations into the murine erythroid response to chronic hypoxia.

During chronic hypoxia, the number of splenic erythroid progenitor cells in mice, particularly CFU-E, increased dramatically but transiently. Since all three classes of erythroid progenitors in the femoral bone marrow were suppressed, a large part of this increase might be attributed to migration of CFU-E and/or their progenitors from the medullary cavity. The changes in CFU-E were preceded 48-72 hours earlier by an increase in serum erythropoietin (Ep) titers which, in turn, had been preceded by a rapid and marked "shift-to-the-right" in the hemoglobin oxygen dissociation curve. During hypoxia, the mice lost a considerable fraction of their body weight. Computer simulations, using a mathematical model of erythropoietic regulation, suggest that this weight loss, either indirectly by reducing the need for red cells in a smaller-than-control animal or by directly altering the sensitivity of the Ep-producing mechanism, is the major cause of the falling Ep titers despite continuation of the hypoxic stress. Because of high endogenous 59Fe incorporation levels, it was not possible to confirm the thesis that animals with an expanded Erythropoietin Responsive Cell (ERC) compartment would be more sensitive to exogenous erythropoietin than are mice with a normal or reduced ERC population.

Animals↗
PubMed1979

A mathematical and experimental simulation of the hematological response to weightlessness.

Two ground-based methods of weightlessness simulation--a computer model of erythropoiesis feedback regulation and bedrest--were used to investigate the mechanisms which lead to loss of red cell mass during spaceflight. Both methods were used to simulate the first Skylab mission of 28 days. Human bedrest subjects lose red cell mass linearly with time and in this study the loss was 6.7% at the end of four weeks (compared to 14% in Skylab). Postbedrest recovery of red cell mass was delayed for two weeks during which time a further decline in this quantity was noted. This is consistent with the first Skylab mission but not with the two longer flights of two and three months. Hemoconcentration, observed early in the study, was essentially maintained despite red cell loss because of continued loss of plasma volume. The computer model, using the time-varying hematocrit data to estimate red cell production rates, predicted dynamic behavior of plasma volume and red cell mass that was in close agreement with the measured values. The results support the hypothesis that red cell loss during supine bedrest is a normal physiological feedback process in response to hemoconcentration enhanced tissue oxygenation and suppression of red cell production. In contrast, the delayed postbedrest recovery of red cell mass was more difficult to explain, especially in the light of enhanced reticulocyte indices observed at the onset on ambulation. Model simulation suggested the possibilities, still to be experimentally demonstrated, that this period was marked by some combination of increased oxygen-hemoglobin affinity, small reductions in mean red cell life span, ineffective erythropoiesis, or abnormal reticulocytosis. The question of whether hemoconcentration is the sole contributor to spaceflight red cell losses also remains to be resolved.

Bed Rest↗
PubMed1978

Evaporative water loss in man in a gravity-free environment.

Daily evaporative water losses (EWL) during the three Skylab missions were measured indirectly using mass and water-balance techniques. The mean daily values of EWL for the nine crew members who averaged 1 h of daily exercise were: preflight 1,750 +/- 37 (SE) ml or 970 +/- 20 ml/m2 and inflight 1,560 +/- 26 ml or 860 +/- 14 ml/m2. Although it was expected the EWL would increase in the hypobaric environment of Skylab (one-third atmosphere). an average decrease from preflight sealevel conditions of 11% was measured. The results suggest that weightlessness decreased sweat losses during exercise and possibly reduced insensible skin losses as well. The weightlessness environment apparently promotes the formation of an observed sweat film on the skin surface during exercise by reducing convective flow and sweat drippage, resulting in high levels of skin wettedness that favor sweat suppression.

Body Water↗
PubMed1977

Observations in energy balance in man during spaceflight.

An investigation was undertaken of the changes in metabolic energy balance which occur in weightlessness. Daily energy intake was determined each day throughout the 28-, 59-, and 84-day flights for each of the nine Skylab astronauts. The energy content of the urine and feces was also measured. Changes in body composition were inferred from measurements of weight, volume, water, and total exchangeable potassium before and after flight. During flight changes were followed by a daily measurement of body mass and by metabolic balance. Examination of the data reveal losses in body weight during the 1st and 2nd mo of flight, a loss in body water and protein during the 1st mo, and a loss of fat during the 1st, 2nd, and 3rd mo of flight. The energy input was about 41.7 kcal/kg per day on the ground, and 43.7 kcal/kg per day after 3 mo in space. The increase in net energy input of about 1.6% per mo is significant (P less than 0.05). When the net energy input is expressed on the basis of total body potassium, the increase in the resulting "noramlized" net energy input of about 3.7% per mo is also significant (P less than 0.05).

Body Composition↗