Karl Kirsch

Differential expression of nitric oxide synthases (NOS 1-3) in human skeletal muscle following exercise countermeasure during 12 weeks of bed rest

Adaptive changes of major body systems in astronauts during spaceflight can be simulated by strict anti‐orthostatic head‐down tilt (HDT) bed rest (BR), a ground‐based microgravity (μG) model that provides a meaningful opportunity to study atrophy mechanisms and possible countermeasures under controlled experimental conditions. As nitric oxide (NO) signaling is linked to muscle activity, we investigated altered expression of the three major isoforms of nitric oxide synthase (NOS 1–3) at cellular compartments during prolonged HDT BR without (control group) and with resistance exercise interventions (exercise group) using a flywheel ergometer (FWE). Atrophy detected in mixed (fast–slow) m. vastus lateralis (VL) and slow‐type m. soleus (SOL) myofiber Types I and II (minus 35–40% of myofiber cross‐sectional area) was prevented by FWE training. Concomitant to muscle atrophy, reduced NOS 1 protein and immunostaining was found in VL not in SOL biopsies. In trained VL, NOS 1 protein and immunostaining at myofibers II were significantly increased at the end of BR. Exercise altered NOS 2/caveolin 3 co‐immunostaining patterns of subsarcolemmal focal accumulations in VL or SOL myofibers, which suggests reorganization of sarcolemmal microdomains. In trained VL, increased capillary‐ to‐fiber (C/F) ratio and NOS 3 protein content were documented. Activity‐linked NO signaling may be widespread in skeletal muscle cellular compartments that may be directly or indirectly impacted by adequate exercise countermeasure protocols to offset the negative effects induced by disuse, immobilization, or extended exposure to microgravity.

Agreement Between 24-Hour Salt Ingestion and Sodium Excretion in a Controlled Environment

Accurately collected 24-hour urine collections are presumed to be valid for estimating salt intake in individuals. We performed 2 independent ultralong-term salt balance studies lasting 105 (4 men) and 205 (6 men) days in 10 men simulating a flight to Mars. We controlled dietary intake of all constituents for months at salt intakes of 12, 9, and 6 g/d and collected all urine. The subjects’ daily menus consisted of 27 279 individual servings, of which 83.0% were completely consumed, 16.5% completely rejected, and 0.5% incompletely consumed. Urinary recovery of dietary salt was 92% of recorded intake, indicating long-term steady-state sodium balance in both studies. Even at fixed salt intake, 24-hour urine collection for sodium excretion (UNaV) showed infradian rhythmicity. We defined a ±25 mmol deviation from the average difference between recorded sodium intake and UNaV as the prediction interval to accurately classify a 3-g difference in salt intake. Because of the biological variability in UNaV, only every other daily urine sample correctly classified a 3-g difference in salt intake (49%). By increasing the observations to 3 consecutive 24-hour collections and sodium intakes, classification accuracy improved to 75%. Collecting seven 24-hour urines and sodium intake samples improved classification accuracy to 92%. We conclude that single 24-hour urine collections at intakes ranging from 6 to 12 g salt per day were not suitable to detect a 3-g difference in individual salt intake. Repeated measurements of 24-hour UNaV improve precision. This knowledge could be relevant to patient care and the conduct of intervention trials.

Erythropoietin production during flights with pressurised aircrafts.

416 Vol 348 • August 10, 1996 SIR—James emphasises the importance of hypoxia as a risk factor for older passengers engaged in long-haul air travel. A cabin altitude of 8000 ft (2438 m), which is equivalent to a cabin ambient pressure of 75·8 kPa, is regarded as the maximum acceptable cabin altitude of modern airliners cruising at altitudes up to 43 000 ft (13 106 m). We have measured oxygen saturation of haemoglobin (SaO 2 ; ear pulse-oximetry) in 15 resting healthy individuals seated in a hypobaric chamber with an inside ambient pressure of 75·8 kPa. Mean SaO 2 was 90% (SD 1·9; range 85–93) after 30 min of exposure. There is considerable interindividual variation in the responses to a lowered partial O 2 pressure. Responses to hypoxic hypoxia include an increase in pulmonary ventilation, which is evident even at 6600 ft (2012 m). However, immobility, cramped seating conditions, and drowsiness might hinder proper respiratory activities. Moreover, the lower ambient pressure in the cabin leads to gastrointestinal distension, which might limit downward movements of the diaphragm. In those who were dozing off in our hypobaric chamber we found much lower SaO 2 levels (80%) at cabin altitudes of 8000 ft (2438 m). when they were stimulated to respire properly, SaO 2 levels increased substantially. Therefore, if airlines’ advice on routine in-flight exercise were also to address proper pulmonary ventilation, both important hypoxia and venous thrombosis might be prevented. For older people, these exercises should not be too strenuous, because strenuous activities might lower their SaO 2 even further. Airlines’ advice should also include recommendations on adequate fluid intake, because the low relative humidity in the cabin could lead to dehydration. The cabin relative humidity from outside fresh air is less than 1%. Moisture from passengers and crew will cause it to increase, depending on the passenger load factor, ventilation rate, temperature, and pressure. During 16 long-haul flights (Boeing 747–400) we found cabin values ranged between 7 and 14% (mean 10%), which is in accord with studies in other types of aircraft, We undertook a pilot study, in which six healthy people were exposed for 8 h to a simulated altitude of 8000 ft and relative humidity of 8–10% and were instructed to drink 2 L in that time. Compared with the control condition (sea level; relative humidity 30–40%), we found an increase of mean plasma osmolality, mean urine osmolality, and urine specific gravity, indicating dehydration. Because dehydration is a risk factor in long-haul air travel, airlines should instruct passengers to take adequate fluids, while avoiding alcohol (diuretic action, cellular dehydration, drowsiness) and carbonated beverages (gastrointestinal distension).

Erythropoietin regulations in humans under different environmental and experimental conditions

In the adult human, the kidney is the main organ for the production and release of erythropoietin (EPO). EPO is stimulating erythropoiesis by increasing the proliferation, differentiation and maturation of the erythroid precursors. In the last decades, enormous efforts were made in the purification, molecular encoding and description of the EPO gene. This led to an incredible increase in the understanding of the EPO-feedback-regulation loop at a molecular level, especially the oxygen-dependent EPO gene expression, a key function in the regulation loop. However, studies in humans at a systemic level are still very scanty. Therefore, it is the purpose of the present review to report on the main recent investigations on EPO production and release in humans under different environmental and experimental conditions, including: (i) studies on EPO circadian, monthly and even annual variations, (ii) studies in connection with short-, medium- and long-term exercise at sea-level which will be followed (iii) by studies performed at moderate and high altitude.

Hypertension, sodium retention, calcium excretion and osteopenia in Dahl rats.

Background Salt-sensitive hypertension in the Dahl rat is associated with abnormalities in both calcium (Ca2+) and sodium (Na+) homeostasis. Objective To test the hypothesis that salt-induced abnormal Ca2+ handling in Dahl salt-sensitive (DSS) rats is associated with negative Ca2+ balance and bone disease. Methods Ca2+ excretion in acute and chronic Na+ loading and electrolyte and water balance were determined by balance studies in Dahl salt-resistant (DSR) and salt-sensitive (DSS) rats fed 8 or 0.1% NaCl for 4 weeks. A dry ashing procedure was used to determine Na+, Ca2+, and water content and their association with blood pressure in the rats. Results When fed 8% NaCl, DSS rats initially maintained a positive Ca2+ balance and showed decreased natriuresis compared with DSR rats. During the course of Na+ loading, DSS rats increased natriuresis and calciuresis. After 4 weeks of salt loading, cumulative Na+ balance was greater and cumulative Ca2+ balance was less in DSS than in DSR rats. In addition, DSS rats developed osteopenia. Bone mineral content correlated inversely with blood pressure in DSS rats. Acute saline volume expansion in DSS rats demonstrated their ability to excrete the Na+ load fully, but led to an exaggerated renal loss of Ca2+ compared with DSR rats. Conclusion DSS, but not DSR, develop Ca2+ loss and ostopenia during chronic Na+ loading. We speculate that Na+ retention in DSS rats fed a high Na+ diet may be in part a compensatory mechanism to maintain Ca2+ balance.

Neopterin, IgG, IgA, IgM, and Plasma Volume Changes During Long-distance Running

Abstract Prolonged physical exercise is associated with several immunological changes, e.g. increase in proinflammatory cytokines, changes in the white blood count etc. Great discrepancies exist with regard to the exercise- induced influence on serum immunoglobulin and neopterin values. One explanation could be the shifts in plasma volume (PV) during and after exercise which might influence plasma concentrations of these parameters. Therefore we investigated the consequences of a marathon race in a homogenous group of experienced runners on plasma volume shifts, serum Immunglobulin and neopterin concentrations. Plasma values with and without correction for plasma volume shifts were compared. PV was significantly diminished after the race (-8.4%) followed by a rise 34h after finish (+8.5%). Serum immunoglobulin IgG, IgA and IgM were increased within the first hours postmarathon and normalized in the recovery period. When chages in PV were considered, only IgA rose significantly. Serum neopterin remained unchanged after the marathon independently whether corrected for PV changes or not. We conclude that the increase in immunoglobulins in our study was mainly the consequence of plasma volume changes. Since neopterin was unchanged we have at least in our study no evidence for exercise-induced activation of the cellular immune system.