Peter Norsk

Vasorelaxation in space

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.

Fluid Shifts, Vasodilatation and Ambulatory Blood Pressure Reduction During Long Duration Spaceflight

Weightlessness in space induces initially an increase in stroke volume and cardiac output, accompanied by unchanged or slightly reduced blood pressure. It is unclear whether these changes persist throughout months of flight. Here, we show that cardiac output and stroke volume increase by 35–41% between 3 and 6 months on the International Space Station, which is more than during shorter flights. Twenty‐four hour ambulatory brachial blood pressure is reduced by 8–10 mmHg by a decrease in systemic vascular resistance of 39%, which is not a result of the suppression of sympathetic nervous activity, and the nightly dip is maintained in space. It remains a challenge to explore what causes the systemic vasodilatation leading to a reduction in blood pressure in space, and whether the unexpectedly high stroke volume and cardiac output can explain some vision acuity problems encountered by astronauts on the International Space Station.

Osmoregulatory control of renal sodium excretion after sodium loading in humans

The hypothesis that renal sodium handling is controlled by changes in plasma sodium concentration was tested in seated volunteers. A standard salt load (3.08 mmol/kg body wt over 120 min) was administered as 0.9% saline (Isot) or as 5% saline (Hypr) after 4 days of constant sodium intake of 75 (LoNa+) or 300 mmol/day (HiNa+). Hypr increased plasma sodium by ∼4 mmol/l but increased plasma volume and central venous pressure significantly less than Isot irrespective of diet. After LoNa+, Hypr induced a smaller increase in sodium excretion than Isot (48 ± 8 vs. 110 ± 17 μmol/min). However, after HiNa+the corresponding natriureses were identical (135 ± 33 vs. 139 ± 39 μmol/min), despite significant difference between the increases in central venous pressure. Decreases in plasma ANG II concentrations of 23-52% were inversely related to sodium excretion. Mean arterial pressure, plasma oxytocin and atrial natriuretic peptide concentrations, and urinary excretion rates of endothelin-1 and urodilatin remained unchanged. The results indicate that an increase in plasma sodium may contribute to the natriuresis of salt loading when salt intake is high, supporting the hypothesis that osmostimulated natriuresis is dependent on sodium balance in normal seated humans.

Underestimation of plasma volume changes in humans by hematocrit/hemoglobin method

During water immersion in humans, the use of changes in hematocrit (Hct) and hemoglobin concentration (Hb) underestimates the relative changes in plasma volume (PV) as measured directly with Evans blue (EB). It is not known whether the same is the case during posture changes. Therefore, changes in PV were determined with an EB dilution technique in 10 males before, during, and after an acute posture change from seated to 6 degrees head-down tilt (HDT). The EB method was improved to take into account changes in transcapillary escape rate of albumin-bound EB. Furthermore, blood was sampled from a central venous catheter. Hct and Hb were simultaneously measured. During HDT, PV determined with EB increased by 9.3 +/- 2.0% but increased only 4.5 +/- 0.9% when calculated with the Hct/Hb method (P < 0.05 vs. EB measurements). Thus use of the Hct/Hb method in humans leads to underestimation of the change in PV by as much as 50% during an acute change in posture. Therefore, a direct tracer-dilution method must be used for accurate estimations of changes in PV during changes in posture or other antiorthostatic maneuvers.During water immersion in humans, the use of changes in hematocrit (Hct) and hemoglobin concentration (Hb) underestimates the relative changes in plasma volume (PV) as measured directly with Evans blue (EB). It is not known whether the same is the case during posture changes. Therefore, changes in PV were determined with an EB dilution technique in 10 males before, during, and after an acute posture change from seated to 6° head-down tilt (HDT). The EB method was improved to take into account changes in transcapillary escape rate of albumin-bound EB. Furthermore, blood was sampled from a central venous catheter. Hct and Hb were simultaneously measured. During HDT, PV determined with EB increased by 9.3 ± 2.0% but increased only 4.5 ± 0.9% when calculated with the Hct/Hb method ( P < 0.05 vs. EB measurements). Thus use of the Hct/Hb method in humans leads to underestimation of the change in PV by as much as 50% during an acute change in posture. Therefore, a direct tracer-dilution method must be used for accurate estimations of changes in PV during changes in posture or other antiorthostatic maneuvers.

Impact of diuretic treatment and sodium intake on plasma volume in patients with compensated systolic heart failure.

In patients with heart failure (HF), the use of diuretics may be a double‐edged sword that can alleviate symptoms of congestion, but also result in over‐diuresis and intravascular volume depletion. The purpose of the present study was to examine plasma volume (PV) in HF patients receiving from 0 to 160 mg of furosemide and to investigate whether determination of plasma N‐terminal fragment of pro‐brain natriuretic peptide (NT‐proBNP) concentrations can predict PV‐status.

Central venous pressure and plasma arginine vasopressin during water immersion in man

SummaryThe influence of increased central venous pressure (CVP) on the plasma concentration of arginine vasopressin (pAVP) was examined in 7 healthy males subjected to water immersion (WI) up to the neck following overnight food- and fluid restriction. During WI the subject sat upright in a pool (water temperature=35.0‡ C) for 6 h. In control experiments the subject assumed the same position outside the pool wearing a water perfused garment (water temperature=34.6‡ C). CVP increased markedly during WI and after 20 min of immersion it attained a level which was significantly higher than the control value (10.9±1.5 (mean ± SE) vs. 2.2±1.3 mm Hg, p<0.01). This increase was sustained throughout the 6 h WI period. Simultaneously, after 20 min pAVP during WI was significantly lower than control values (1.8±0.3 vs. 2.2±0.3 pg·ml−1, p<0.05) and sustained throughout WI. Systolic arterial pressure increased significantly by 7–10 mm Hg (p<0.05) after 2 h of WI, while diastolic arterial pressure was unchanged. Heart rate was decreased by 10 bpm throughout immersion. There was no change in plasma osmolality when comparing control with immersion. A pronounced osmotic diuresis, natriuresis and kaliuresis occurred during WI, counteracting an acute significant increase in plasma volume of 6.5±1.9% (P<0.01 within 20 min of immersion). We conclude that an increase in CVP due to WI is accompanied by suppressed pAVP.

Preventing hemodilution abolishes natriuresis of water immersion in humans

The hypothesis was tested that hemodilution is one of the determinants of the water immersion (WI)-induced natriuresis. Eight males were subjected to 3 h of 1) WI to the midchest (Chest), 2) WI to the neck combined with thigh cuff-induced (80 mmHg) venous stasis (Neck + stasis), and 3) a seated time control (n = 6). Central venous pressure and left atrial diameter increased to the same extent during Chest and Neck + stasis (P < 0.05), whereas renal sodium excretion only increased during Chest from 77 +/- 7 to 225 +/- 13 micromol/min (P < 0.05). During Chest, plasma colloid osmotic pressure (COP) decreased from 27.7 +/- 0.7 to 25.1 +/- 0.7 mmHg (P < 0.05), and plasma volume (PV) increased from 3,263 +/- 129 to 3,581 +/- 159 ml (P < 0.05), whereas these variables remained unchanged during Neck + stasis. Plasma norepinephrine concentration decreased similarly during Chest and Neck + stasis by 45 +/- 7 and 34 +/- 4%, respectively (P < 0.05), whereas plasma renin activity decreased only during Chest (P < 0.05). In conclusion, during WI in humans 1) hemodilution (decrease in COP and increase in PV) is a pivotal stimulus for the natriuresis and 2) central blood volume expansion without hemodilution does not augment renal sodium output.The hypothesis was tested that hemodilution is one of the determinants of the water immersion (WI)-induced natriuresis. Eight males were subjected to 3 h of 1) WI to the midchest (Chest), 2) WI to the neck combined with thigh cuff-induced (80 mmHg) venous stasis (Neck + stasis), and 3) a seated time control ( n = 6). Central venous pressure and left atrial diameter increased to the same extent during Chest and Neck + stasis ( P < 0.05), whereas renal sodium excretion only increased during Chest from 77 ± 7 to 225 ± 13 μmol/min ( P < 0.05). During Chest, plasma colloid osmotic pressure (COP) decreased from 27.7 ± 0.7 to 25.1 ± 0.7 mmHg ( P< 0.05), and plasma volume (PV) increased from 3,263 ± 129 to 3,581 ± 159 ml ( P < 0.05), whereas these variables remained unchanged during Neck + stasis. Plasma norepinephrine concentration decreased similarly during Chest and Neck + stasis by 45 ± 7 and 34 ± 4%, respectively ( P < 0.05), whereas plasma renin activity decreased only during Chest ( P < 0.05). In conclusion, during WI in humans 1) hemodilution (decrease in COP and increase in PV) is a pivotal stimulus for the natriuresis and 2) central blood volume expansion without hemodilution does not augment renal sodium output.

The paradox of systemic vasodilatation and sympathetic nervous stimulation in space

Cardiac output is increased by some 18% by weightlessness during the initial week of spaceflight compared to upright standing or sitting on the ground and more so during the initial days of flight than at the end. In addition, mean 24-h diastolic, but not systolic pressure, is significantly decreased by 5mmHg. This is in accordance with observations that very acute weightlessness during parabolic airplane flights and a week of weightlessness in space leads to a decrease in systemic vascular resistance. That the arterial resistance vessels are dilated in space is in contrast to the augmented sympathetic nervous activity and decreased urine production, which have consistently been observed in astronauts in space. These contrasting observations require further investigation.

Vasopressin, angiotensin II and renal responses during water immersion in hydrated humans

1 The hypothesis was tested that in hydrated humans the release of arginine vasopressin and angiotensin II is suppressed by water immersion (WI) and that this is a mechanism of the immersion‐induced diuresis and natriuresis. Seven male subjects on controlled sodium (65‐75 mmol per 24 h for 4 days) and water intake were studied. 2 Plasma vasopressin was promptly suppressed by WI, declining from 0·76 ± 0·13 to 0·23 ± 0·08 pg ml−1 (P < 0·05), with a concomitant increase in renal water output (CH2O) from ‐0·4 ± 0·2 to 4·4 ± 0·7 ml min−1 (P < 0·05). Subsequently, CH2O returned to the level of control, whereas plasma vasopressin remained suppressed. Plasma osmolality gradually increased from 285 ± 1 to 289 ± 1 mosmol kg−1 (P < 0·05). WI caused a 9‐fold increase in renal sodium excretion. Plasma angiotensin II decreased from 27·1 ± 5·3 to 4·3 ± 0·7 pg ml−1 (P < 0·05), and the intraindividual correlation coefficients between sodium excretion rates and angiotensin II concentrations varied between 0·73 and 0·96 (P < 0·002). 3 The data demonstrate that plasma vasopressin and angiotensin II concentrations decrease during WI in hydrated humans, concomitantly with initial increases in CH2O and sodium excretion. Therefore, vasopressin could constitute a mediator of CH2O and angiotensin II of the natriuresis of WI. The subsequent return of CH2O to the level of control is, however, also caused by other factors.

Mechanisms of increase in cardiac output during acute weightlessness in humans

Based on previous water immersion results, we tested the hypothesis that the acute 0-G-induced increase in cardiac output (CO) is primarily caused by redistribution of blood from the vasculature above the legs to the cardiopulmonary circulation. In seated subjects (n = 8), 20 s of 0 G induced by parabolic flight increased CO by 1.7 ± 0.4 l/min (P < 0.001). This increase was diminished to 0.8 ± 0.4 l/min (P = 0.028), when venous return from the legs was prevented by bilateral venous thigh-cuff inflation (CI) of 60 mmHg. Because the increase in stroke volume during 0 G was unaffected by CI, the lesser increase in CO during 0 G + CI was entirely caused by a lower heart rate (HR). Thus blood from vascular beds above the legs in seated subjects can alone account for some 50% of the increase in CO during acute 0 G. The remaining increase in CO is caused by a higher HR, of which the origin of blood is unresolved. In supine subjects, CO increased from 7.1 ± 0.7 to 7.9 ± 0.8 l/min (P = 0.037) when entering 0 G, which was solely caused by an increase in HR, because stroke volume was unaffected. In conclusion, blood originating from vascular beds above the legs can alone account for one-half of the increase in CO during acute 0 G in seated humans. A Bainbridge-like reflex could be the mechanism for the HR-induced increase in CO during 0 G in particular in supine subjects.