Lower body negative pressure (LBNP) is a stimulus frequently used to study reflex circulatory responses in humans. Studies have provided data on LBNP-induced blood pooling; however, the possibility that LBNP also might be associated with an important loss of plasma fluid has attracted little attention. Therefore this problem was analysed in male volunteers exposed to prolonged (10 min) high (70-75 mmHg) LBNP. Data on LBNP-induced blood pooling that were more reliable than in previous literature were also provided. LBNP caused early pooling of more than 870 ml of blood. Rapid filtration of plasma into the exposed tissues occurred throughout LBNP. The cumulative oedema in the legs and buttocks averaged as much as 460 ml, and additional quite large volumes of plasma apparently accumulated in other parts of the lower body. Concomitantly, there was compensatory absorption of extravascular fluid in the upper body. The net decrease in plasma volume (PV) was still large and averaged 491 +/- 29(SE) ml. Two aspects of the demonstrated process of transcapillary fluid fluxes and PV decline may be emphasized. Firstly, in conjunction with the primary large redistribution of intravascular volume, it certainly implies that LBNP is a potent stimulus as also indicated by a progressive increase in heart rate (HR) and a progressive decline in systolic pressure throughout experimental intervention. In fact, LBNP-induced circulatory stress clearly has bearings on the extreme hypovolaemic situation provided by the pressure-bottle haemorrhage technique used in animals. Secondly, it not only offers an interesting example of the dynamics of PV but appears to have more general validity with regard to states characterized by gravitational shifts of blood (hydrostatic load), like upright exercise and quiet standing.

The hypothesis was tested that the hemoconcentration observed during standing provides erroneous information about the induced plasma volume (PV) decline. Male volunteers (n = 10) stood quietly for 15 min after supine rest. On standing arterial hemoglobin (Hb) rose slowly to reach an increase of 5.9 +/- 0.3% (SE) after 15 min. Early after resuming the supine position, Hb increased further to 9.2 +/- 0.5% above control level and then declined gradually. Venous antecubital blood from the left arm supported horizontally at heart level in both the supine and standing positions (no hydrostatic load) showed very similar changes. However, Hb in venous blood collected during standing from the right arm held in the natural dependent position rose much more markedly than that in arterial blood and in venous blood from the horizontal arm (470 +/- 122, 105 +/- 24, and 55 +/- 7% greater increase at 5, 10, and 15 min, respectively). Taken together, these observations indicated that 1) analyses of arterial blood sampled from the standing subject grossly underestimated the prevailing "overall" hemoconcentration and PV decline, a phenomenon ascribed to incomplete mixing of blood between dependent and nondependent regions; 2) arterial blood sampled from the recumbent subject early (60 s) after completion of standing reflected the "true" overall intravascular hemoconcentration, with a calculated PV decline of no less than 511 +/- 27 ml, because the supine position facilitated proper mixing of blood between circulatory compartments; 3) data from common venous sampling from the dependent arm during standing primarily reflected a regional hemoconcentration (fluid loss) in the arm rather than PV decline; and 4) short-term quiet standing caused a more prominent and hemodynamically important decrease in PV than usually believed.

Plasma volume (PV) changes to 15 min quiet standing were analysed (Hb/Hct-alterations) in two studies (nine and 11 healthy males). Data confirmed and extended our findings that blood, arterial or venous, sampled on standing fails to reveal the induced overall haemoconcentration (PV loss). First, standing led to markedly incomplete mixing of blood between circulatory compartments. Secondly, with sampling of antecubital venous blood, haemoconcentration was strongly affected by regional plasma loss and, apparently equally important, by regional blood flow. These difficulties were circumvented, however, by the finding that the PV restitution (haemoconcentration) in the recumbent subject after standing fitted invariably a monoexponential function with striking precision. It allowed, by extrapolation, a seemingly superior definition of the PV reduction at the very end of standing as supported by the fact that PV changes from Hb/Hct and from IgM protein concentration changes were similar, refuting that Fcell-changes contributed to the pronounced Hb/Hct changes. The described novel approach revealed a nicely reproducible PV loss of no less than 692 +/- 46 mL (18.1 +/- 0.6%, Study I; 18.4 +/- 0.5%, Study II), or approximately 11% reduction of blood volume, showing that quiet standing leads to a much more rapid and haemodynamically important decrease in PV than reported previously. Yet, PV was virtually restored within 20 min of recumbency after standing, with 50% recovery within 6 min and regain of as much as 70 mL in the very first min. The latter data indicate that the body possesses a surprising capacity for rapid fluid transfer from the extra- to the intravascular space.

The plasma volume (PV) decline upon 1.5, 3, 5, 8, 10, 15 and 35 min periods of quiet standing was studied (Hb/Hct) in male volunteers (n = 7). This approach permitted detailed definition of the time-course of the volume change. PV decreased by as much as 8.5 +/- 0.4% (328 +/- 15 mL) after 3 min standing and by no less than 11.7 +/- 0.4% (466 +/- 22 mL) after 5 min. The reduction was 14.3 +/- 0.7, 16.8 +/- 0.8, 17.7 +/- 0.8 and 17.4 +/- 0.9% after 8, 10, 15 and 35 min, or 568 +/- 30, 671 +/- 39, 707 +/- 41 and 691 +/- 44 mL. These data, in conjunction with the 1.5 min experiments, indicated a very rapid approximately 125 mL min-1 fluid loss initially on standing. However, the PV loss showed marked decline with time and was virtually completed within 10 min. Finally, the observation was made that the rate of PV recovery after standing was inversely related to the duration of standing. It is suggested that (a) the transcapillary hydraulic conductivity in the dependent limbs, the predominant targets for fluid filtration on standing, is about 0.010 mL min-1 100 mL-1 mmHg-1 and much greater than indicated previously. However, protective mechanisms restrict rapid fluid loss to early phases of standing. (b) Decrease in PV may contribute importantly to haemodynamic stress and to orthostatic, fainting reactions during short quiet standing. Apparently, PV loss may be equally important as pooling of blood, traditionally regarded as a dominant cause of adverse orthostatic reactions. (c) The duration of standing, as such, may be critical for the rate of PV recovery after standing.

Seven healthy males were exposed to quiet standing (15 min) after supine rest. Alterations in the total mass of plasma proteins were analysed from changes in plasma volume (PV; determination of control PV and subsequently of induced per cent PV changes using Hb/Hct) and protein concentration as revealed in arterial blood collected after standing. This approach adopted the concept that valid data on overall circulatory haemoconcentrations prevailing on standing can only be reached when blood is sampled on resumption of the recumbent posture, whereas conventional sampling from the standing subject provides erroneous information. The PV reduction on standing averaged 649 +/- 65 mL (16.9 +/- 1.0%). There were very similar net decreases in plasma (serum) total protein (7.6 +/- 0.8 g) and albumin (7.8 +/- 0.9 g). These findings permitted the following main conclusions of physiological and methodological pertinence: (1) Quiet standing leads to a clear-cut net decrease in the plasma protein content predominantly confined to albumin, in all probability via convection secondary to PV loss by filtration in dependent regions. (2) It is suggested that the albumin loss reflects a quite high capillary macromolecular permeability in the dependent limbs on standing preferentially confined to skin/subcutaneous tissues. (3) The albumin loss implies that plasma concentration changes of neither albumin nor of total protein can be used to describe the PV loss on standing. However, concentration changes of the plasma globulin fraction as a whole, expressed by the difference (total protein-albumin), seem to reflect PV alterations approximately.