INTRODUCTION

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THE OSMOTIC CONDUCTANCE of the lung (K, the product of the reflection coefficient for the solute, , and the filtration coefficient of the capillary endothelium including its total surface area, K) has been estimated from the dilution of plasma indicators in pulmonary venous blood (3), the density reduction of pulmonary venous or aortic blood (11, 12), or the weight change of isolated perfused lungs (20, 26, 28) after the injection or infusion of various low-molecular-weight (LMW) solutes into the pulmonary artery or vena cava. Because of nonuniform velocity distribution in vessel flow, irregular flow distribution among microvessels, and the mixing of the heart, the blood flow through the pulmonary circulation and the heart chambers is dispersive in nature. This dispersion effect, along with the tissue effect (the change in tissue osmotic pressure to counter the hypertonic disturbance), was not considered in most of the above estimations. Utilizing a compartmental model to describe the extraction process and an analytic model to characterize dispersion in the pulmonary circulation, Hunter and Lee (11) showed that the dispersion and the tissue effects can significantly alter the estimation of K .

The density-measuring technique has a much higher sensitivity to measure changes in hematocrit (or hemoglobin content) than an optical technique (11). As a result, Hunter and Lee (11) could still assess K for a hypertonic disturbance at the site of infusion approximately one order of magnitude smaller than that used by Effros (3) and Semler et al. (23). The finding of similar density dilution results for isolated rabbit lungs perfused with blood or autologous plasma by Hunter and Lee leads to the conclusion that the reduced disturbance does not impede red blood cell (RBC) flow, and thus the fluid extraction from the tissue is the only factor producing the observed density reduction. In this study we extend the in vitro infusion protocol of Hunter and Lee (11) to an in vivo condition and incorporate the dispersion analysis of Hunter and Lee (10) and Audi et al. (1) to interpret the measured density dilution in terms of K. Our first objective is to assess how the hypertonic disturbance of five LMW solutes (NaCl, urea, glucose, sucrose, and raffinose) produces a transcapillary fluid exchange with the tissue, determine the role of the tissue in the exchange process, and assess the dependence of K on the test solutes.

The tissue is separated from the plasma by a semipermeable membrane. In formulating the governing equations for the extraction process, we consider that the infused hypertonic disturbance extracts from the tissue a fluid with a low, but constant, osmotic pressure over the course of the experiment. It is this hypotonic extraction that changes the tissue osmotic pressure. Under this framework, the extraction process "sees" the change in plasma osmotic pressure, not the test solute producing the hypertonicity. This implication leads to the hypothesis that the tissue fluid volume estimated from the density reductions of the five LMW solutes should be identical. Our second objective is to evaluate and test the validity of this hypothesis.

Hypertonic solutions have been used in the treatment of hemorrhagic shock and pulmonary edema (24, 27). The pathophysiology of lung diseases such as acute respiratory distress syndrome has been associated with increased pulmonary permeability (14). Improved understanding of the hypertonic infusion therapy and characterization of the pulmonary permeability could facilitate the development of treatment and prevention of these diseases.

	MATERIALS AND METHODS

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Surgical preparation. Sixteen New Zealand White male rabbits weighing 2.91 ± 0.04 (SE) kg were sedated with chlorpromazine (6.7 mg/kg body wt im) and anesthetized with pentobarbital sodium (20 mg/kg) injected into the lateral vein of the ear. After the administration of lidocaine to the areas of incision, the trachea, right common carotid artery, left femoral artery, and both jugular veins were isolated. A tracheostomy was performed, and the rabbit was allowed to spontaneously ventilate. An arterial catheter was inserted 5 cm into the carotid artery to reach the aorta, and heparin (3,000 U/kg) was infused for anticoagulation. The remaining isolated vessels were cannulated after a 5-min waiting period to allow steady-state distribution of heparin.

Measurement systems. Aortic blood was withdrawn from the arterial catheter at a rate of 30 ml/min with a Masterflex roller pump. The blood was pumped through the U tube of a density meter (model DMA 602W, Mettler-Parr) and returned via a catheter inserted through the left jugular vein into the vena cava. The density meter was incorporated with an IBM personal computer to form the density-measuring system (DMS). The density of the aortic blood flowing through the U tube is identified as _a. Its value before a hypertonic infusion is designated ₀.

Experimental protocol. Typically, three infusions of each test solution were administered to each rabbit. Each infusion constituted part of an individual run, which was randomized for each rabbit. The first eight rabbits were infused with only NaCl, urea, and glucose. The last eight were given all five test solutions. At the beginning of each run, an 0.8-ml bolus of isotonic saline was injected within 0.5 s into the jugular vein. The transient decrease in _a was recorded for later computation of the cardiac output (), the mean transit time (MTT) from the injection site to the sampling site, the midpoint of the U tube (t_m), and the transport function of the circulation situated between the two sites [h(t)] (11). After the blood density had stabilized, the hypertonic solution was infused at a rate _inf (3.8 ml/min, which is 2% of ) for 20 s while the blood density was measured. A typical record of the changes in blood density and infusion pressure is depicted in Fig. 1. Approximately 15 min were allowed between runs for the blood density to stabilize to a new steady-state value. If the systemic arterial and central venous pressures were altered by 10 mmHg, then the run was neglected (~2% of all data collected).

View larger version (23K): [in this window] [in a new window]   Fig. 1.   A: aortic blood density (a) change resulting from a 20-s hypertonic NaCl jugular infusion at time 0. Rapid transient density decrease indicates a quick extraction from lung tissue. It is followed by a rapid density increase: result of filtration of fluid to lung tissue. tr, Appearance time of recirculation. Pulmonary extraction is completed before recirculation. Smooth solid curve drawn on experimental data represents density response due to fluid extraction from peripheral organs. B: hydrostatic pressure at infusion site (Pinj) showing time course of 20-s infusion.

Hypertonic disturbance. We prepared the hypertonic test solution by dissolving solid NaCl, urea, glucose, sucrose, and raffinose in isotonic saline. The osmolarities of these solutions above the isotonic saline level (_h) were 2,100, 2,400, 2,155, 1,200, and 600 mosmol/l for NaCl, urea, glucose, sucrose, and raffinose, respectively. With NaCl as the most abundant solute in the plasma, the other solutes are each 2% of the plasma concentration of NaCl (8). As a result, the small infusion rate has a negligible dilution effect (1%) on the solutes and resident NaCl in the plasma. The only osmotic disturbance is caused by the hypertonicity above the isotonic level. Because of the exchanges across the RBC membrane and the concentration dependence of the hemoglobin osmotic coefficient (25), the role of RBCs in the hypertonic disturbance could be accounted for by excluding a  fraction of the RBC volume from the dilution blood volume. With these considerations, the following equation can be derived to predict the temporal increase in the plasma osmotic pressure due to the infused solute [_pl,inf (t)]

(Eq. 1)

where _max is _infh/[(1  H)] and u(t) is a unit step function. The replacement of u(t) by u(t)  u(t  20 s) simulates the current protocol of a 20-s infusion with no recirculation. Solomon et al. (25) and Gary-Bobo and Solomon (7) reported that the  for NaCl and glucose is ~0.54, which is used to analyze the results of all test solutes.

Stream-tube model. We model the flow from the injection site to the sampling site as a bundle of parallel stream tubes (15) and gather stream tubes having an MTT within  and  + d as a group. Let h() be the fractional flow distribution so that the blood flow passing through this stream-tube group is prescribed as h()d. In a stream tube in this group, flow dispersion is characterized by the transport function h_s(t,). Their interrelations with the overall flow and transport function yield the following two identities

(Eq. 2)

(Eq. 3)

In the dispersion analysis of Hunter and Lee (10),  is the subscript i identifying the group, h()d is _i, h_s(t,) is h_i(t), and [ ]d is [ ].

(Eq. 4)

(Eq. 5)

(Eq. 6)

(Eq. 7)

Distributions of surface area and tissue volume. Let the total surface area of the lung for exchange be S. The more capillaries are in a stream-tube group, the higher is its total blood flow and the larger its total surface area available for transcapillary fluid movement. Accordingly, we assume for later analysis that the surface area of the stream-tube group [S* ()d] has the same fractional distribution as the flow, i.e.

(Eq. 8)

In addition, we regard that the tissue thickness surrounding the capillary and the volume fraction of the tissue participating in the extraction process are the same for all capillaries. Let the initial tissue fluid volume be V_ti,0. With these two descriptions of the tissue compartment and Eq. 8, the tissue volume for the stream-tube group is V_ti,0h()d.

Driving pressures. The analysis of the hypertonic results indicates that the maximum rate of fluid extraction is 2% of the rate of blood flow. The blood flow along the capillary can therefore be regarded as constant. As examined later, the permeation of test solutes across the capillary wall (i.e., the exchange surface) may be so slow that its role in changing the plasma or tissue osmotic pressure of test solutes can be much smaller than that induced by the rapid extraction. As a result, we also regard the plasma osmotic pressure of the test solute along the capillary as constant. Consequently, the only change in the plasma osmotic pressure "seen" by the capillary (_pl,c) is the hypertonic input (Eq. 1) dispersed by the arterial dispersion, which is

(Eq. 9)

where _pl,inf is change in osmotic pressure at site of infusion. One-half of the capillary MTT is used in the delta function to time the event at the midpoint of the capillary, as suggested by the analysis of Friend and Lee (6).

(Eq. 10)

Tissue volume change. Suppose the filtration coefficient (including the total surface area) is K. As specified earlier, Sh()d is the surface area of the stream-tube group. Thus its filtration coefficient is Kh()d. Let the rate of filtration through the capillary wall be J_s(t,)hd. With these two definitions and the conclusion in Driving presssures, the simplification of the generalized Starling equation (Eq. 7 in Ref. 19) to the current infusion protocol leads to the following rate of filtration, which is the first derivative of the change in the tissue fluid volume [V_ti(t,)]

(Eq. 11)

where  is the reflection coefficient of the capillary wall for the test solute and _f is the reflection coefficient of the abundant solute in the tissue. We use d/dt to represent the time derivative, as  is constant for the stream-tube group. Substituting Eqs. 9 and 10 into Eq. 11 and reorganizing Eq. 11, we find that the tissue fluid volume change is governed by the following differential equation

(Eq. 12)

where

(Eq. 13)

This expression for , being independent of  and test solute and having the unit of seconds¹, allows us to regard it as a rate constant universal among all stream-tube groups and for all test solutes.

Density change. Solving Eq. 12 for a zero initial volume change and then finding J_s through the equality in Eq. 11, we have

(Eq. 14)

where g(t) = exp(t)u(t). For the capillaries in the stream-tube group, the flow rate is h()d and the density of blood is ₀. The extraction adds to the flow at the rate J_s(t,)h()d and with the density _f. The mixing of these two fluid flows and the omission of higher-order terms produce the following density change

(Eq. 15)

With the dispersion from the capillary to the sampling site as [t  (  t_n)/2]  h_pv(t), we have the density change exiting the stream tube at the sampling site [_s(t,)] as

(Eq. 16)

With the flow of the stream-tube group as h()d, the application of mass conservation principle to the mixing of flows with variable density changes (10) yields the following density change in the sampling site _a(t) which is also the aortic blood density change

(Eq. 17)

With the help of Eqs. 3 and 6, the substitution of Eqs. 14-16 into Eq. 17 yields

(Eq. 18)

The equation deduced for hypertonic NaCl infusion by Hunter and Lee (10) is a special case of Eq. 18 once  is identified as  of NaCl. Their derivation requires no assumption on having the input transport functions to capillaries prescribed by h_pa(t).

Computation of K, , and V_ti,0. The computer program developed by Hunter and Lee (10) was used for the computation. First, the transient density decrease from the isotonic injection is revised by subtracting the density oscillation extended from the ventilatory density oscillation before the injection. The revised decrease (Fig. 2A, dashed line) is used to determine the area (A), , and MTT t_m. Along with the second and third moments, a lagged normal density function is constructed as h(t). The solid line in Fig. 2A is Ah(t) so calculated. Because the infusate density (_inf) may be different from the blood density (₀), the infusion imposes on _a an infusion "artifact" described by (_inf  0)(_inf/)[u(t)  u(t  20 s)]  h(t). The program subtracts from _a (Fig. 1A) the ventilatory oscillation and infusion artifact. The revised density change subsided within 15 s after the infusion. We integrate the change over this period to find an area A' and a first moment t'_m.

View larger version (12K): [in this window] [in a new window]   Fig. 2.   A: reduction in a due to injection of isotonic saline (dashed line). Ventilatory oscillations have been removed. Solid line, fit generated from a lagged normal density function. B: transport function (dashed line) for a stream tube with same mean transit time (MTT) as fit shown in A (solid line). C: distribution of flow among stream-tube groups as a function of MTT of stream tube. h(t), Transport function of circulation between injection and sampling site; A, area; subscripts s, , and c: stream tube, cardiac output, and capillary.

(Eq. 19)

(Eq. 20)

(Eq. 21)

Rate of fluid extraction. The rate of extraction for each stream-tube group is J_s(t,)h()d. Its sum over all groups is the total rate of fluid extracted for the entire lung

(Eq. 22)

The factoring out of the convolution and the use of the identity 2(2t) = (t) reduce Eq. 22 to

(Eq. 23)

The integration of J_f (t) from 0 to  is the maximum reduction in tissue volume. Let it be V_ti,max. Because of the integration of h_pa(t), 2h_c(2t) and g(t) is all unity, we have

(Eq. 24)

Let the MTT of h_pa(t) be t_pa. The MTT of the transport function in brackets in Eq. 23 is t_pa + t_c /2. In reference to the overall MTT t_m, the partition fraction q is 1  (t_pa + t_c /2)/t_m. The procedure to partition the overall transport function h(t) yields an arterial transport function h_a(t), with an MTT, t_a, equal to (1  q)t_m (10). For the particular case that q = 0.5 and h_pa(t) equals h_pv(t), we find that h_a(t) has a second and a third central moment slightly larger than that within brackets in Eq. 23. Without precise measurement of h_pa(t) and h_pv(t), it may be appropriate to approximate the function within brackets as h_a(t) for computing J_f (t).

Statistics. Values are means ± SE. For evaluation of statistical difference, a two-way, randomized incomplete block analysis of variance is applied. Differences are considered significant if P < 0.05 (analysis of variance). When significance is determined by analysis of variance, a Newman-Keuls multiple comparison test is used to identify the differences among the means.

View larger version (13K): [in this window] [in a new window]   Fig. 3.   A: revised a change from Fig. 1 (dashed line) with model prediction of pulmonary extraction and filtration superimposed (solid line). B: theoretical prediction of change in aortic plasma osmolarity (a). Its difference from a step increase at time 0 and a step decrease at 20 s reflects effect of flow dispersion.

	RESULTS

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Table 1 lists the body weight, the lung blood volume, the pulmonary blood flow, and the six moments in Eq. 5 for the in vitro experiments of Audi et al. (1) and Hunter and Lee (11) and for the current in vivo experiments. and are indexes describing the dispersion (or spread) of h_c and h, respectively. We term the ratio / as the fractional dispersion in the pulmonary capillary flow. For the perfusion system of Audi et al., the tabulated value for the ratio indicates that the heterogeneity in capillaries contributes to a fractional dispersion of 79%. Because the catheter delay formed a larger fraction of t_m for the in vitro lung system of Hunter and Lee, the system's capillary heterogeneity makes up a smaller fractional dispersion (61%). The tabulated value of / for the current in vivo experiments indicates that the capillary heterogeneity makes up only 30% of the total dispersion. This smallest fractional dispersion results from the presence of the heart chambers in the in vivo system, the dispersion induced by the mixing action of the chambers, and the smallest fraction of t_c in t_m.

Taking as 70% of (Table 1), we calculate h_s(t) of a stream tube having the same MTT as the overall transport function h(t). Both are depicted in Fig. 2B for comparison. The transport function for the capillaries ( being 30% of ) is depicted in Fig. 2C, with the time axis shifted by t_n. As demonstrated earlier, this function also describes the fractional flow distribution as a function of the MTT of the stream tubes.

A typical density response to a 20-s infusion of hypertonic saline into the rabbit's vena cava is shown in Fig. 1A. The step change in plasma osmotic pressure at the infusion site is depicted in Fig. 1B, with _max = 28.7 mosmol/l. In the isotonic injection experiment done 2 min earlier, was 435 ml/min and MTT was 4.7 s. The revised density, the measured density with the effects of ventilation and infusion artifact removed, is illustrated in Fig. 3A. Because the hypertonic saline has a density of 1,041.48 g/l and the average blood density is 1,041.67 g/l, the effect of density difference is negligible in this particular case. The K calculated for this example is 18.2 ml · h¹ · mosmol¹ · l, the rate constant  is 0.44 s¹, the tissue volume participating in the extraction process (V_ti,0) is 2.7 ml, and the volume extracted (V_ti,max) is 0.3 ml.

The solid curve superimposed on the revised density change in Fig. 3A is the theoretical prediction of Eq. 18 expanded to cover the extraction and filtration induced by the 20-s infusion under the assumption of no recirculation. The coefficient of variation for the record over the first 12 s is 0.07, indicating a good fit. Figure 3B shows the variation in hypertonicity in the aortic blood passing through the DMS calculated as _max[u(t)  u(t  20 s)]h(t).

The density response to an infusion of hypertonic saline in the in vitro experiment of Hunter and Lee (11) clearly shows that the extraction transient is followed by a filtration transient. In addition to these two transient changes, the in vivo results show a third density change, a slow decrease over the latter one-half of the response (Fig. 1A). Also shown in Fig. 1A is a recirculation time (t_r). This time is determined from the injection of isotonic saline earlier in the run. The coincidence of this time with the initiation of the third density change indicates that the change results from fluid extraction in peripheral organs after the passage of the hypertonic disturbance. For reference, we identify the third density phase as peripheral exchange. The extended density record indicates that the maximum decrease in density is reached at 50 s. The density fully returns to the preinfusion level within the next 10-15 min.

As shown later, the density responses of the four other solutes, after revision for the infusion artifact, exhibit these three features: pulmonary extraction, pulmonary filtration, and peripheral exchange. Because there is no peripheral exchange over the phase of pulmonary extraction, it is analyzed by the program to obtain the K and tissue fluid volume participating in the extraction.

To better understand the dynamics of extraction and filtration leading to the observed density variation shown in Fig. 3A, we apply the partition analysis of Hunter and Lee (10) to the stream-tube transport function shown in Fig. 2B to calculate the expected change in capillary osmotic pressure, the tissue osmotic pressure, the rate of fluid extraction, and the _a exiting the stream tube. Their dynamics are depicted in Fig. 4. For this example, the maximum rate of fluid extraction is ~1% of the blood flow through the stream tube. The extraction ceases as the osmotic pressure of NaCl, the most abundant solute in tissue fluid, increases to a level in balance with the elevated plasma osmotic pressure of the test solute. In the case in which the abundant solute is different from the test solute, their concentrations will be equilibrated by permeation. The minimal change in _a after the cessation of fluid extraction indicates that the permeations may not alter the net osmotic pressure difference between the tissue and plasma to produce a fluid filtration capable of changing the density of blood leaving the capillary.

View larger version (12K): [in this window] [in a new window]   Fig. 4.   Filtration dynamics for stream tube characterized by Fig. 2. A: change in capillary plasma osmolarity (c) and tissue fluid osmolarity (ti) expected with a 28.8 mosmol/l, 20-s hypertonic infusion for stream tube with transport function in Fig. 2B. B: transcapillary fluid flux (Jf). C: predicted change in a.

Figure 5A shows a typical density response to a 20-s infusion of hypertonic urea. The hypertonic disturbance (_max) is 33.6 mosmol/l. is 423 ml/min, and t_m is 4.8 s. The dashed curve depicts the infusion artifact due to the density difference between the infusate and the blood. The density response shown in Fig. 5B is revised for the effects of ventilation and the infusion artifact. In this example for urea,  is 0.47 s¹, K is 16 ml · h¹ · mosmol¹ · l, V_ti,0 is 2.3 ml, and the coefficient of variation is 0.08.

View larger version (14K): [in this window] [in a new window]   Fig. 5.   Density change in response to a 20-s infusion of hypertonic urea [maximum elevation in osmotic pressure during infusion (max) = 30 mosmol/l]. A: aortic density change (solid line) and expected density change due only to density difference between blood (1,041.73 g/l) and hypertonic solution (1,033.33 g/l, dashed line). B: revised density with model prediction superimposed. Extraction parameters are given in RESULTS.

The density response to a 20-s infusion of hypertonic glucose is illustrated in Fig. 6A. The hypertonic infusion caused a _max of 24.5 mosmol/l. is 328 ml/min, and t_m is 5.7 s. The hypertonic glucose has a density of 1,105 g/l, which causes the blood density to increase by 0.5 g/l and masks the extraction and filtration components of the density response (solid line) by the infusion artifact (dashed line). The revised density change (Fig. 6B) reveals distinctly the pulmonary extraction and filtration. For this glucose result, K is 24.5 ml · h¹ · mosmol¹ · l, V_ti,0 is 3.4 ml,  is 0.30 s¹, and the coefficient of variation is 0.14. 

View larger version (17K): [in this window] [in a new window]   Fig. 6.   Density response to a 20-s infusion of hypertonic glucose (max = 30 mosmol/l). A: aortic density change (solid line) and expected density change due only to density difference between blood (1,039.47 g/l) and hypertonic solution (1,108.60 g/l, dashed line). B: revised density with model prediction superimposed. Extraction parameters are given in RESULTS.

Figures 7 and 8 show typical density responses to hypertonic solutions of sucrose and raffinose, respectively. Similar to the response to the hypertonic glucose solutions, once the overwhelming infusion artifact is removed, the features of pulmonary extraction and then filtration are indicated by Figs. 7B and 8B. For sucrose, _max is 20.4 mosmol/l, is 272 ml/min, t_m is 5.4 s, K is 18.1 ml · h¹ · mosmol¹ · l, V_ti,0 is 3.6 ml,  is 0.33 s¹, and the coefficient of variation is 0.15. For raffinose, _max is 7 mosmol/l, is 375 ml/min, t_m is 4.7 s, K is 27 ml · h¹ · mosmol¹ · l, V_ti,0 is 5.4 ml,  is 0.33 s¹, and the coefficient of variation is 0.10. 

View larger version (18K): [in this window] [in a new window]   Fig. 7.   Density response to a 20-s infusion of hypertonic sucrose (max = 20.4 mosmol/l). A: aortic density change (solid line) and expected density change due only to density difference between blood (1,040.97 g/l) and hypertonic solution (1,108.64 g/l, dashed line). B: revised density with model prediction superimposed. Extraction parameters are given in RESULTS.

View larger version (13K): [in this window] [in a new window]   Fig. 8.   Density response to a 20-s infusion of hypertonic raffinose (max = 8.8 mosmol/l). A: aortic density change (solid line) and expected density change due only to density difference between blood (1,039.47 g/l) and hypertonic solution (1,085.64 g/l, dashed line). B: revised density with model prediction superimposed. Extraction parameters are given in RESULTS.

The 16 rabbits used in this study weighed 2.91 ± 0.04 kg. The aortic hematocrit of the rabbits was 36.2 ± 0.3%. The average measured in this study was 386 ± 7 ml/min. The MTT from the infusion site to the sampling site was 5.02 ± 0.06 s. Blood density averaged 1,040.07 ± 0.26 g/l. Arterial pressure averaged 71.5 ± 0.9 mmHg, and the venous pressure was 2.0 ± 0.3 mmHg. Plasma osmolarity was measured in 10 rabbits before the hypertonic infusion every third run over the course of the experiment. The results indicate that the plasma osmolarity returned to baseline conditions during the 15-min recovery period allowed between each infusion. The plasma density after the 15-min recovery period also returned to its baseline value. The _inf, _max, A', t'_m, , coefficient of variation, V_ti,max, V_ti,max/_max, K, and V_ti,0 for the five solutes are tabulated in Table 2. The last four values have been normalized by the wet lung weight estimated from an empirical factor of 4 g wet lung/kg body wt (10).

Statistically, our results show no significant difference among the values of  and among V_ti,0, indicating their independence of the molecular size of the test solutes (Fig. 9). This independence is consistent with the theoretical consideration used to formulate Eq. 12, which specifies  as a rate constant characterizing the extraction of a hypotonic fluid containing the LMW solutes in the tissue fluid. The relationship between K and the molecular size of the test solute is shown in Fig. 10. The positive slope of the relationship indicates that more fluid, for the same osmotic disturbance, is extracted with larger solutes.

View larger version (10K): [in this window] [in a new window]   Fig. 9.   A: extraction rate constant () obtained from each test solute (, from left to right: NaCl, urea, glucose, sucrose, and raffinose) as a function of solute radius. B: initial tissue fluid volume (Vti,0) calculated from density response of each solute (symbols same as in A). These results demonstrate that  and Vti,0 are independent of solute causing extraction, which is consistent with hypothesis in text.

View larger version (13K): [in this window] [in a new window]   Fig. 10.   Osmotic conductance (K) as a function of molecular radius for NaCl, urea, glucose, sucrose, and raffinose (, left to right).

	DISCUSSION

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Density change during the extraction phase. The density of the infused hypertonic solution is different from the density of blood. This infusion artifact has been corrected from the measured change in _a. A 30 mosmol/l increase in plasma NaCl osmotic pressure causes fluid extraction from the RBCs and reduces the RBC volume by 6% (25). This redistribution of fluid between RBCs and plasma reduces the hematocrit by 2% but has no effect on the blood density. Because the transit of plasma through the pulmonary vasculature is only slightly longer than the transit of RBCs, the small fluid redistribution contributes minimally to the observed change in _a.