[How can human beings perform in the outer space? Exercise in space].
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Publications and source records attributed to Peter Norsk.
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Patients with untreated heart failure (HF) exhibit a blunted hemodynamic and neuroendocrine response to a high sodium intake, leading to excessive sodium and water retention. However, it is not known whether this is the case for patients with compensated HF receiving angiotensin-converting enzyme inhibitors and beta-adrenoreceptor blockers. Therefore, we determined the hemodynamic and neuroendocrine responses to 1 wk of a low-sodium diet (70 mmol/day) and 1 wk of a high-sodium diet (250 mmol/day) in 12 HF patients and 12 age-matched controls in a randomized, balanced fashion. During steady-state conditions, hemodynamic and neuroendocrine examinations were performed at rest and during bicycle exercise. In seated HF patients, high sodium intake increased body weight (1.6 +/- 0.4%), plasma volume (9 +/- 2%), cardiac index (14 +/- 6%), and stroke volume index (21 +/- 5%), whereas mean arterial pressure was unchanged. Therefore, the total peripheral resistance decreased by 10 +/- 4%. Similar hemodynamic changes were observed during an incremental bicycle exercise test. Plasma concentrations of angiotensin II and norepinephrine were suppressed, whereas plasma pro-B-type natriuretic peptide remained unchanged. In conclusion, high sodium intake was tolerated without any excessive sodium and water retention in medically treated patients with compensated HF. The observation that high sodium intake improves cardiac performance, induces peripheral vasodilatation, and suppresses the release of vasoconstrictor hormones does not support the advice for HF patients to restrict dietary sodium.
During everyday life, gravity constantly stresses the cardiovascular system in upright humans by diminishing venous return. This decreases cardiac output and induces systemic vasoconstriction to prevent blood pressure from falling. We therefore tested the hypothesis that entering weightlessness leads to a prompt increase in cardiac output and to systemic vasodilatation and that these effects persist for at least a week of weightlessness in space. Cardiac output and mean arterial pressure were measured in 8 healthy humans during acute 20-s periods of weightlessness in parabolic airplane flights and on the seventh and eighth day of weightlessness in 4 astronauts in space. The seated 1-G position acted as reference. Entering weightlessness promptly increased cardiac output by 29+/-7%, from 6.6+/-0.7 to 8.4+/-0.9 L min(-1) (mean+/-SEM; P=0.003), whereas mean arterial pressure and heart rate were unaffected. Thus, systemic vascular resistance decreased by 24+/-4% (P=0.017). After a week of weightlessness in space, cardiac output was increased by 22+/-8% from 5.1+/-0.3 to 6.1+/-0.1 L min(-1) (P=0.021), with mean arterial pressure and heart rate being unchanged so that systemic vascular resistance was decreased by 14+/-9% (P=0.047). In conclusion, entering weightlessness promptly increases cardiac output and dilates the systemic circulation. This vasorelaxation persists for at least a week into spaceflight. Thus, it is probably healthy for the human cardiovascular system to fly in space.
We tested the hypothesis that sympathoadrenal activity in humans is low during spaceflight and that this effect can be simulated by head-down bed rest (HDBR). Platelet norepinephrine and epinephrine were measured as indexes of long-term changes in sympathoadrenal activity. Ten normal healthy subjects were studied before and during HDBR of 2-wk duration, as well as during an ambulatory study period of a similar length. Platelet norepinephrine concentrations (half-life = 2 days) were studied in five cosmonauts, 2 wk before launch, within 12 h after landing after 11-12 days of flight, and at least 2 wk after return to Earth. Because of the long half-life of platelet norepinephrine, data obtained early after landing would still reflect the microgravity state. Platelet norepinephrine decreased markedly during HDBR (P < 0.001), whereas there were no significant changes when subjects were ambulatory. Platelet epinephrine did not change during HDBR. During microgravity, platelet norepinephrine and epinephrine increased in four of the five cosmonauts. Platelet norepinephrine concentrations expressed in percentage of preflight and pre-HDBR values, respectively, were significantly different during microgravity compared with HDBR [153 +/- 28% (mean +/- SE) vs. 60 +/- 6%, P < 0.004]. Corresponding values for platelet epinephrine were also significant (293 +/- 85 vs. 90 +/- 12%, P < 0.01). The mechanism of the platelet norepinephrine and epinephrine response during spaceflight flight is most likely related to the concomitant decrease in plasma volume. HDBR cannot be applied to simulate changes in sympathoadrenal activity during microgravity.
One of the most important methodological problems of the foreign gas rebreathing technique is that outcome of the measurements depends on procedural variables such as rebreathing frequency (RF), rebreathing bag volume (V(reb)), lung volume at start of rebreathing and intervals between measurements. Therefore, in 10 healthy males we investigated the effects of changes in ventilation pattern on cardiac output (CO) estimated by an N(2)O-rebreathing technique. Reducing the rebreathing volume (V(reb)) from 1.5 to 1.0 l diminished CO by 0.5 +/- 0.2 l min(-1), whereas an increase in V(reb) from 1.5 to 2.5 l had no effects. CO was 1.0 +/- 0.2 l min(-1) higher when, rebreathing was performed after a forced expiration than following a normal tidal expiration. Serial determinations of CO required a 3-min interval between the measurements to avoid effects of recirculation of N(2)O. Changing RF from 15 to 30 breaths min(-1) or adding serial dead space by up to 600 ml did not affect the determination of CO. In conclusion, the rebreathing procedure for determination of CO at rest should be performed following a normal tidal expiration with a rebreathing bag volume of between 1.5 and 2.5 l and with manoeuvres separated by at least 3-5 min. Variations in RF within the physiological range from 15 to 30 breaths min(-1) do not affect outcome of the measurements.
The human cardiovascular system and regulation of fluid volume are heavily influenced by gravity. When decreasing the effects of gravity in humans such as by anti-orthostatic posture changes or immersion into water, venous return is increased by some 25%. This leads to central blood volume expansion, which is accompanied by an increase in renal excretion rates of water and sodium. The mechanisms for the changes in renal excretory rates include a complex interaction of cardiovascular reflexes, neuroendocrine variables, and physical factors. Weightlessness is unique to obtain more information on this complex interaction, because it is the only way to completely abolish the effects of gravity over longer periods. Results from space have been unexpected, because astronauts exhibit a fluid and sodium retaining state with activation of the sympathetic nervous system, which subjects during simulations by head-down bed rest do not. Therefore, the concept as to how weightlessness affects the cardiovascular system and modulates regulation of body fluids should be revised and new simulation models developed. Knowledge as to how gravity and weightlessness modulate integrated fluid volume control is of importance for understanding pathophysiology of heart failure, where gravity plays a strong role in fluid and sodium retention.
High (n = 7, 25 +/- 2 yr) and low (n = 8, 26 +/- 3 yr) lower body negative pressure (LBNP) tolerant men were exposed to -15 mmHg (for 12 min) followed by -50 mmHg (for 21 min) to test the hypothesis that heart rate (HR) and blood pressure (BP) data from acute exposure to LBNP would not discriminate between the higher and lower tolerance men. Central venous pressure (CVP), HR, and systolic (SBP) and diastolic (DBP) blood pressures measured before and at 15-s intervals during LBNP and calculated mean arterial pressure (MAP), pulse pressure (PP), and work of the heart (HW) were analyzed using ANOVA (p < or = 0.05). There were no significant changes in HR, SBP, DBP, MAP, PP, or HW during exposure to -15 mmHg LBNP. Throughout -50 mmHg LBNP, there were no significant changes in SBP, MAP, PP, or HW, but HR increased significantly (high tolerance by 30%, low tolerance by 40%) with no difference between groups. Diastolic blood pressure changed by +7.6 % (NS) in the high group and by -3.3% (NS) in the low group; the initial exposure to -50 mmHg resulted in a significant difference between groups for the first 45 s. Central venous pressure decreased significantly at -15 mmHg (high group by -33%, low group by -38 %) and at -50 mmHg (high group by -70%, low group by -73%) with no difference between groups. Thus, HR and BP responses at -15 and -50 mmHg of LBNP for 30 min do not discriminate between the high and low tolerant men and questions the validity and usefulness of the clinical stand test to predict orthostatic tolerance.
BACKGROUND: Physiological changes occur in man during space missions also at the renal level. Proteinuria was hypothesized for space missions but research data are missing. METHODS: Urinary albumin, as an index of proteinuria, and other variables were analyzed in 4 astronauts during space missions onboard the MIR station and on the ground (control). Mission duration before first urine collection in the four astronauts was 4, 26, 26, and 106 days, respectively. On the ground, data were collected 2 months before mission in two astronauts, 6 months after in the other astronauts. A total of twenty-two 24-hour urine collections were obtained in space (n per astronaut = 1-14) and on the ground (n per astronaut = 2-12). Urinary albumin was measured by radioimmunoassay. For each astronaut, mean of data in space and on the ground was defined as individual average. RESULTS: The individual averages of 24 h urinary albumin were lower in space than on the ground in all astronauts; the difference was significant (mean +/- SD, space and on the ground = 3.41 +/- 0.56 and 4.70 +/- 1.20 mg/24 h, p = 0.017). Dietary protein intake and 24-hour urinary urea were not significantly different between space and on the ground. CONCLUSIONS: Urinary albumin excretion is low during space mission compared to data on the ground before or after mission. Low urinary albumin excretion could be another effect of exposure to weightlessness (microgravity).
The hypothesis was tested that cardiac output (CO) and stroke volume (SV) are increased by a moderate physiological elevation in sodium intake with a more pronounced effect in the ambulatory upright seated than supine position. Fourteen healthy males were investigated during ambulatory and controlled laboratory conditions at the end of two consecutive 5-day periods with sodium intakes of 70 (low) and 250 (high) mmol/24 h or vice versa, respectively. Comparing high and low sodium intake, plasma volume and plasma protein concentrations were 9 and 8% higher in the seated and the supine position, respectively. When seated during laboratory conditions, CO was 5.3 +/- 0.2 l/min on the high sodium intake vs. 4.8 +/- 0.2 l/min on the low (P < 0.05), and SV was 81 +/- 3 vs. 68 +/- 3 ml (P < 0.05). In the supine position, SV was 107 +/- 3 ml on the high vs. 99 +/- 3 ml (P < 0.05) on the low sodium intake, while CO remained unchanged. The difference in CO and SV induced by the change in sodium intake was significantly higher in the seated than in the supine position (P < 0.05). During upright ambulatory conditions, CO was 5.9 +/- 0.2 l/min during the high and 5.2 +/- 0.2 l/min during the low sodium intake (P < 0.05), and SV was 84 +/- 3 and 69 +/- 3 ml (P < 0.05), respectively. Mean arterial pressure was unchanged by the variations in sodium intake. In conclusion, increments in sodium intake within the normal physiological range increase CO and SV and more so in the seated vs. the supine position. These changes are readily detectable during upright, ambulatory conditions. The results indicate that the higher SV and CO could constitute an arterial baroreflex stimulus for the augmented renal sodium excretion.
The hypothesis was tested that suppression of generation of ANG II is one of the mechanisms of the water immersion (WI)-induced natriuresis in humans. In one protocol, eight healthy young males were subjected to 3 h of 1) WI (WI + placebo), 2) WI combined with ANG II infusion of 0.5 ng. kg(-1). min(-1) (WI + ANG II-low), and 3) a seated time control (Con). In another almost identical protocol, 7-10 healthy young males were investigated to delineate the tubular site(s) of action of ANG II by the lithium clearance method (C(Li)) and were on an additional fourth study day subjected to infusion of ANG II at a rate of 1.5 ng. kg(-1). min(-1) (WI + ANG II-high). During WI + placebo, plasma concentration of ANG II decreased from 16 +/- 2 to 8 +/- 1 pg/ml (P < 0.05) and renal sodium excretion increased from 104 +/- 15 to 294 +/- 27 micromol/min (P < 0.05). During WI + ANG II-low, plasma ANG II was not suppressed by WI, and the natriuresis was blunted by 52 +/- 13% (P < 0.05). During WI + ANG II-low and WI + ANG II-high, an increase in C(Li) was prevented that was otherwise observed during WI, and fractional distal reabsorption of sodium was facilitated. In conclusion, maintaining plasma concentration of ANG II unchanged at the level of control attenuates the natriuresis of WI considerably in humans. Therefore, suppression of generation of ANG II is an important mechanism of the natriuresis of WI in humans. Furthermore, infusion of ANG II during WI prevents an otherwise induced increase in C(Li) and facilitates the fractional distal reabsorption of sodium, probably via an effect on aldosterone release.
The hypothesis was tested that changing the direction of the transverse gravitational stress in horizontal humans modulates cardiovascular and renal variables. On different study days, 14 healthy males were placed for 6 h in either the horizontal supine or prone position following 3 h of being supine. Eight of the subjects were in addition investigated in the horizontal left lateral position. Compared with supine, the prone position slightly increased free water clearance (349 +/- 38 vs. 447 +/- 39 ml/6 h, P = 0.05) and urine output (1,387 +/- 55 vs. 1,533 +/- 52 ml/6 h, P = 0.06) with no statistically significant effect on renal sodium excretion (69 +/- 3 vs. 76 +/- 5 mmol/6 h, P = 0.21). Mean arterial pressure and left atrial diameter were similar comparing effects of supine with prone. The prone position induced an increase in heart rate (54 +/- 2 to 58 +/- 2 beats/min, P < 0.05), total peripheral vascular resistance (13 +/- 1 to 16 +/- 1 mmHg. min(-1). l(-1), P < 0.05), forearm venous plasma concentration of norepinephrine (97 +/- 9 to 123 +/- 16 pg/ml, P < 0.05), and atrial natriuretic peptide (49 +/- 4 to 79 +/- 12 pg/ml, P < 0.05), whereas stroke volume decreased (122 +/- 5 to 102 +/- 3 ml, P < 0.05, n = 6). The left lateral position had no effect on renal variables, whereas left atrial diameter increased (32 +/- 1 to 35 +/- 1 mm, P < 0.05) and mean arterial pressure decreased (90 +/- 2 to mean value of 85 +/- 2 mmHg, P < 0.05). In conclusion, the prone position reduced stroke volume and increased sympathetic nervous activity, possibly because of mechanical compression of the thorax with slight impediment of arterial filling. The mechanisms of the slightly augmented urine output in prone position require further experimentation.
The hypothesis was tested that acute water immersion to the neck (WI) compared with 6 degrees head-down tilt (HDT) induces a more pronounced distension of the heart and lower plasma levels of vasoconstrictor hormones. Ten healthy males underwent 30 min of HDT, WI, and a seated control (randomized). During WI, left atrial diameter and stroke volume increased to the same extent as during HDT. Cardiac output increased by 1 l/min more during WI than during HDT. (P < 0.05). Plasma atrial natriuretic peptide increased during WI (P < 0.05) but not during HDT, whereas plasma norepinephrine, vasopressin, and renin activity were suppressed similarly. Mean arterial pressure decreased by 9 mmHg (P < 0.05) during HDT and was unchanged during WI, and heart rate decreased more during HDT (P < 0.05). Arterial pulse pressure increased considerably more during HDT than during WI. In conclusion, the hypothesis was not confirmed because the cardiac atria were similarly distended by acute HDT and WI and the release of vasoconstrictor hormones were suppressed to the same extent.
Values of effective pulmonary blood flow (Q(EP)) and cardiac output, determined by a non-invasive foreign gas rebreathing method (CO(RB)) using a new infrared photoacoustic gas analysing system, were compared with measurements of cardiac output obtained by the direct Fick (CO(FICK)) and thermodilution (CO(TD)) methods in patients with heart failure or pulmonary hypertension. In 11 patients, of which three had shunt flow through areas without significant gas exchange, the mean difference (bias) and limits of agreement (+/- 2 S.D.) were 0.6 +/- 1.2 litre x min(-1) when comparing CO(FICK) and Q(EP), and -0.8 +/- 1.3 litre x min(-1) when comparing CO(FICK) and CO(TD). When correction for intrapulmonary shunt flow was applied (i.e. calculation of CO(RB)) in all 11 patients, the bias between CO(FICK) and CO(RB) was 0.1 +/- 0.9 litre x min(-1), primarily because agreement improved in the three patients with significant shunt flow. In the eight patients without significant shunt flow, the agreement between Q(EP) and CO(FICK) was 0.3 +/- 0.9 litre x min(-1). In conclusion, a foreign gas rebreathing method with a new infrared photoacoustic gas analyser provided at least as reliable a measure of cardiac output as did thermodilution. In the absence of significant shunt flow, measurement of Q(EP) itself provides a reliable estimate of cardiac output in heart failure patients. The infrared photoacoustic gas analyser markedly facilitates clinical use of the rebreathing method in general, which makes the method available to a larger group of clinicians working with patients with cardiovascular diseases.
Proteinuria was hypothesized for space mission but research data are missing. Urinary albumin, as index of proteinuria, was analyzed in frozen urine samples collected by astronauts during space missions onboard MIR station and on ground (control). Urinary albumin was measured by a double antibody radioimmunoassay. On average, 24h urinary albumin was 27.4% lower in space than on ground; the difference was statistically significant. Low urinary albumin excretion could be another effect of exposure to weightlessness (microgravity).