THE HEMATOCRITOF THE LESSER CIRCULATION IN MAN1'2

By LAWRENCES. LILIENFIELD, RENATOD. KOVACH, PAUL A. MARKS,3 LEEM. HERSHENSON,4GERALDP. RODNAN,4FRANKLIN G. EBAUGH,JR.,5

ANDEDWARDD. FREIS

(From the Cardiovascular Research Laboratory, Georgetotm University Medical Center, Wash-ington, D. C., the Veterans Administration Hospital, Washington, D. C., and the

National Institute of Arthritis and Metabolic Diseases, National Institutesof Health, Bethesda, Maryland)

(Submitted for publication October 3, 1955; accepted August 17, 1956)

A discrepancy appears to exist between totalblood volume as calculated from albumin spaceand large vessel hematocrit, and total blood vol-ume as calculated from red cell volume and thishematocrit (1, 2). The hematocrit as measuredon arterial or venous blood indicates a ratio ofred cell volume to plasma volume that is higherthan the total body red cell volume to total bodyplasma volume ratio. Fahraeus (1) in 1921 per-formed experiments with blood flowing throughfine glass capillaries in which he demonstrateda lower hematocrit in the fine capillaries than inthe larger entrance or exit vessels. It was postu-lated that this phenomenon was due to laminarflow with axial streaming of red cells and con-sequent excess of plasma. Hence, the concept ofa "small vessel or capillary hematocrit" was con-ceived.

Freis, Stanton and Emerson (3), using T-1824dye and differential agglutination of red cells(Ashby technique), studied the transit times ofplasma and red cells through the human forearmand found a more rapid circulation for red cellsthan for plasma. Lawson, Overbey, Moore andShadle (4) studied the pulmonary circulation indogs with T-1824 dye and p82 tagged red cells.These authors concluded that the hematocrit ofthe pulmonary capillaries was much lower than

'Presented in part at the National Meeting of TheAmerican Federation for Clinical Research, Atlantic City,New Jersey, May 1, 1955.

2Supported in part by the U. S. Public Health ServiceGrant H 1903 (National Heart Institute).

Present address: Department of Medicine, Collegeof Physicians and Surgeons, Columbia University, NewYork.

4Present address: Department of Medicine, Universityof Pittsburgh School of Medicine, Pittsburgh, Pa.

5 Present address: Hitchcock Foundation, Hanover,New Hampshire.

that of the peripheral blood. Although Lawson'sfindings were consistent with a "small vessel he-matocrit" concept, differences between methodsused to measure red cell transit times and plasmatransit times might well have affected his results.

Analysis of the data of Freis' experiments wouldindicate that the differences in transit times foundwere of insufficient magnitude to account for alowering of the "small vessel hematocrit" by axialstreaming of red cells. In an attempt to explorethis phenomenon further, an investigation wasmade of the hematocrit of the pulmonary circula-tion in man.

MATERIALS ANDMETHODS

Eighteen studies were performed on thirteen patientswithout cardiovascular or pulmonary disease. Twentyml. of a subject's blood was incubated for one hour atroom temperature in a Fenwal bottle containing 9 ml. ofN.I.H. Solution B acid citrate dextrose solution and ap-proximately 50 to 100 microcuries of Na,Cr'O, equivalentto 25 to 200 micrograms of chromium metal. The mix-ture was centrifuged and the supernatant plasma removed.The bottle was then refilled with normal saline solution,mixed, recentrifuged and the saline supernatant removed.This was repeated until the washing saline was free ofradioactivity. Twenty microcuries of I' tagged humanserum albumin was then added with sufficient saline toreconstitute the suspension to 20 ml. After thorough mix-ing a portion of this suspension was removed for analy-sis. The remainder (approximately 5 ml.) was then in-jected rapidly with a calibrated syringe into the circulationof the subject. In eleven cases the injection was madeinto an antecubital vein and in seven cases into the mainpulmonary artery through a cardiac catheter.

Samples of blood were collected continuously at two-second intervals for one minute from a femoral arterythrough a seventeen gauge thin-wall needle via a shortlength of rubber tubing. The blood drained into paraf-fined test tubes containing one drop of dried heparin solu-tion. Following collection of the samples, blood was takenfor hematocrit determinations in Wintrobe tubes (2,000 Gfor 60 minutes). One or two ml. samples of the re-

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LILIENFIELD ET AL.

TABLE I

Pulmonary blood flow from tagged red cells and tagged plasma albumin

Total blood flowTotal flow

Arterial Plasma Red cell Plasma flow Red cell flow from RBCInjection hematocrit flow flow 100-Hct./100 Hct./100 Total flow

Subject site % m./sec. ml./sec. ml./sec. ml./sec. from plasma

V. C. 35.0 53.9 30.9 82 88 1.07W. W. 41.6 92.1 65.0 1u5 156 1.01A. G. 43.0 56.2 39.6 99 92 .93E. B. 41.4 54.8 38.5 94 93 .99W. T. Ante- 37.0 170.5 96.2 271 260 .96R. B. cubital 39.0 49.6 35.5 81 91 1.12M. S. vein 45.5 46.1 37.4 84 82 .98J. M. 44.0 76.5 63.5 137 144 1.05F. I. 38.2 57.6 35.5 93 93 1.00J. P. 44.5 61.3 45.0 110 102 .93P. R. 43.4 95.7 66.0 169 152 .90

V. K. 43.0 34.6 26.7 61 62 1.02L. J. 38.2 62.4 38.4 101 101 1.00M. S. Pulmo- 45.5 66.9 52.9 123 116 .94J. M. nary 42.5 69.3 49.8 121 117 .97F. I. artery 38.2 50.6 32.0 82 84 1.02J. P. 44.5 60.1 41.0 106 92 .87P. R. 42.8 61.1 50.1 107 117 1.09

Average 115 113 .99

S.D. .06

maining blood were pipetted into vials and centrifuged.The supernatant plasma was removed and 0.5 ml. pipettedonto planchettes containing a few granules of dry de-tergent. The red cells remaining in the vials werewashed three times with normal saline and the Cr' ac-tivity of the erythrocytes determined in a scintillationwell-type counter. I' activity of the plasma aliquotswas determined with an end-window Geiger-Mueller

250-

200-

tube after drying. A portion of the original injectatewas analyzed in a similar manner. Because of highactivity only 0.1 ml. aliquots were used for red cell ac-tivity measurement and I' activity of the supernatantwas determined after dilution 1:250 times with saline.Counts of Cr51 were converted to counts per ml. redcells from the hematocrit of the samples.

No correction for trapped plasma was made since

PULMONARYBLOOD FLOWFROM 1131 a CR51

a = FLOW CALCULATEDFROMCa5n 0o= o o o

(00 150-

E

0 0

UL. -_

0 I[

AVERAGERATIO = .99 ± .06

FIG. 1. COMPARISONOF PULMONARYBLOODFLOw CALCULATEDFROMLARGE VESSEL HEMATO-CRIT ANDEITHER TAGGEDRED CELLS OR TAGGEDPLASMA

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HEMATOCRITOF THE LESSER CIRCULATION 18

TABLE II

Red cell and plasma volumes of central circulation(volumne =mean circulation time X flow)

Meancirculation ~~~~~~~~~CentralMaciction hematocrittime ~~~~~~~~~~~~~~~~~(Hct.,)Arteral

Red Plasma Red RBCvolume hema-cells albumin cell Plasma RBC Plasma tocrit

Injection (Trb.) (T5) Tra volume volume Vol. + Vol. (Hct..L) Hct.LoSubject site sec. sec. TPMi. "a. % Hct..,

V. C. 18.8 19.1 .99 581 1,027 36.4 35.0 1.04W. W. 13.2 13.1 1.01 857 1,204 41.5 41.6 1.00A. G. 17.4 17.8 .98 687 1,000 40.7 43.0 .95E. B. 22.7 23.8 .95 875 1,304 40.2 41.4 .97W. T. Ante- 10.2 10.9 .94 981 1,858 34.6 37.0 .94R. B. cubital 16.8 17.6 .95 596 837 40.6 39.0 1.04M. S. vein 31.6 31.7 1.00 1,182 1,461 44.7 45.5 .98J. M. 14.7 15.0 .98 933 1,148 44.8 44.0 1.02F. I. 25.8 26.3 .98 916 1,515 37.7 38.2 .99J. P. 16.3 16.9 .96 734 1,036 41.5 44.5 .93P. R. 18.4 19.1 .96 1,214 1,828 43.2 43.4 1.00

Average 18.7 19.2 .97 867 1,296 .99

S.D. 4-02 4-04

V. K. 11.6 12.4 .94 310 429 40.3 43.0 .94L. J. 12.5 13.0 .96 480 811 35.5 38.2 .93M. S. Pulmo- 15.5 15.5 1.00 820 1,037 45.5 45.5 1.00J. M. nary 10.1 10.3 .98 502 714 45.9 42.5 1.08~F. I. artery 13.7 14.3 .96 438 724 38.6 38.2 1.01J. P. 11.6 12.3 .94 476 739 39.2 44.5 .88P. R. 11.5 11.6 .99 576 708 42.2 42.8 .99

Average 12.4 12.8 .97 515 737 .98

S.D. -+.02 -+-07

the hematocrits of the inj ectate and the samples weredetermined in the same manner. The Cr'1 counts wereplotted logarithmically against time, zero time beingdesignated as the midpoint of the interval required forinjection (usually two to five seconds). After extra-polation of the downslope of the resultant curve, thepulmonary red cell flow and mean circulation time werecalculated by application of the Stewart-Hamilton prin-ciple (5). Similarly, the I'~ counts were plotted and theplasma flow calculated, as well as the plasma albuminmean circulation time. The calculation of flow and meancirculation time from the curves was performed em-ploying a method of mathematical integration to infinitetime (6).

The red cell volume and plasma volume of the cen-tral circulation were computed applying the formula:volume equals mean circulation time multiplied by flow.The hematocrit of the lesser circulation was taken as theratio of the red cell volume to the sum of the red cell vol-ume plus plasma volume. Hematocrits also were cal-culated directly from the ratio of mean circulation timesas discussed later.

RESULTS

Total blood flows calculated from either taggedred cells or plasma and the arterial hematocrit

were almost identical (Table I, Figure 1 ). Theratio of these simultaneously but independentlymeasured flows was .99 (S.D. ±- .06).

The circulating red cell volumes, plasma vol-umes and the hematocrits of the lesser circulationare tabulated in Table IL. The upper portion ofthe table refers to the data obtained following ante-cubital vein injections; the lower portion refersto the data obtained following pulmonary injection.The ratio of central circulation to large vessel he-matocrit averaged .99 ±- .04 (S.D.) followingperipheral injection and .98 ±-.07 (S.D.) followingcentral injection. This table also indicates themean circulation time for red cells and plasmafrom each injection site. In both series the ratioof red cell to plasma mean transit times averaged.97 ±- .02 (S.D.), a figure not significantly dif-ferent from unity (P > .05).

The total circulating central blood volumes (redcell plus plasma volumes) measured by antecubi-tal vein injection averaged 2,163 ml. as comparedto 1,252 ml. following pulmonary artery injection.

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LILIENFIELD ET AL.

TABLE III

Red cell and plasma volumes cakulad from extrapolatddownslopes of plotted curvs foUowing

antecubika vesn injction(volume = flow per downslope)

1/Downslope

Red Plasma Red cell Plasmacells albumin volume volume

Subject sec. sec. ml. ml.

V. C. 10.5 10.8 324 579W. W. 4.8 4.2 312 387A. G. 6.4 6.5 253 365E. B. 8.3 8.5 320 466W. T. 3.1 3.3 298 566R.B. 3.8 4.1 135 203M. S.* 10.2 10.0 381 461

1.M.* 4.7 4.6 298 352F.LI.* 7.9 7.8 279 446

J.P.* 3.7 4.0 167 245P.R.* 4.8 4.4 317 416

Average 280 408

* Subjects also had measurements made following pul-monary artery injection. See Table IV.

The large volume after antecubital vein injectioncan be explained by the fact that it includes thevenous volume from the site of injection and allpossible equitemporal injection sites.

"Pulmonary" volumes were also calculated fromthe extrapolated downslopes of the plotted curvesaccording to the method described by Newman,Merrell, Genecin, Monge, Milnor and McKeever(7). The average total "pulmonary" blood volumemeasured 688 ml. following antecubital vein in-jection and 231 ml. following pulmonary artery in-jections (Tables III and IV). The possibilityexists that this difference resulted from incomplete

mixing of the indicators with pulmonary arteryblood when injected through the catheter. Underthis condition only a portion of the pulmonaryblood volume would be measured. However, thismarked difference in apparent pulmonary bloodvolume as measured by the Newmantechnique in-cludes in the group five patients who had succes-

sive determinations made from both injection sites.In each of these five cases, the volume measuredfollowing antecubital vein injection was two andone-half to three times that calculated followingpulmonary artery injection. It would seem un-

likely that incomplete mixing, which should giverandom results, could account for the fairly con-

stant relationship observed. Similar changes indownslope with varying injection sites, under con-

ditions in which incomplete mixing was more

probably not a factor, have been reported byHetzel, Swan and Wood in an even larger numberof patients (8). It is more likely that, underconditions of peripheral injection, the largest vol-ume in the series through which the indicators arediluted includes the venous system and perhapsthe right heart. Hence, the slope following periph-eral injection would measure this volume ratherthan that of the lung. On the assumption that theslope following pulmonary artery injection meas-ures pulmonary volume, the hematocrit of this"pulmonary" vasculature was calculated. Theratio of "pulmonary" to large vessel hematocritagain in these cases averaged .98 (S.D. .05)(Table IV, Figure 2).

TABLE IV

"Pulmonary" red cell and plasma volumes and "pulmonary" Iemaocrit following pulmonary artery injection(from volume flotw per downslope)

1/DownslopeRed

Red Plasma cell Plasma "Pulmonary" Arterialcels albumin volume volume hematocrit hematocrit Pum. Hct.Subject sec. sec. Mi. ml. % 5 Art. Hct.

V. K. 2.4 2.8 64 95 40.3 43.0 .94L. J. 2.0 2.3 77 140 35.5 38.2 .93M. S.* 2.9 2.7 151 181 45.5 45.5 1.00J. M.* 2.0 1.8 100 118 45.9 42.5 1.08F. I.* 2.7 2.7 86 137 38.6 38.2 1.01J. P.* 2.4 2.3 106 138 43.4 44.5 .98P. R.* 1.9 2.1 93 128 42.2 42.8 .98

Average 2.33 2.39 97 134 .98

S.D. ;.05

* Subjects also had measurements made following antecubital vein injection. See Table III.

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HEMATOCRITOF THE LESSER CIRCULATION

"PULMONARY" HEMATOCRITVS LG. VESSEL HEMATOCRITPULMONARYARTERY INJECTION OF INDICATOR

0 - PULMONARYHCT

U s LG. VESSEL HCT50-

40 -

,= 30-<)U04 20-

xa10

0AVERAGE RATIO - .98± .05

FIG. 2. COMPARISONOF HEMATOCRITSCALCULATEDFROM "PUL-MONARY" VOLUME MEASUREMENTS(NEWMANMETHOD) WITHLARGE VESSEL HEMATOCRITSIN SEVEN SUBJECTS

DISCUSSION

These data demonstrate that during one circu-lation there is no measurable loss of tracer albuminby this method in the pulmonary capillaries. Hadthere been utilization, the total blood flow as cal-culated from tagged albumin would have been sig-nificantly higher than the total blood flow as cal-culated from the tagged red cells. Since the cal-culated blood flows are essentially identical thehematocrit of the lesser circulation can be recalcu-lated directly from the ratio of mean circulationtime of red cells to mean circulation time of plasmaalbumin as follows:

Vrbc = Frbc X Trbe (1)

and

VP, = Fpl X Tpl (2)where V, F, and T represent volume, flow andmean circulation time of red cells (rbc) andplasma (pl).

The central hematocrit (He) then is given byVrbe Frbc X Trbe

, Vrb + Vpl Frbc X Trbc + Fpl X Tpl (Since values of total pulmonary blood flow

calculated on the basis of the large vesselhematocrit (HI,) and the distribution of taggedred cells, or tagged plasma protein, are identical,

Frbc Fpl (4)H1v 1 - H1(v

or by rearrangement,

Frbe _ HivFpl 1-H Hi (5)

Substituting (5) into (3), and after rearrange-ment, we now have

Trbo

H0= Tb 1-(6p)Hec = r _

Tpa, H rv

When the central circulation hematocrits cal-culated from equation six are compared to thelarge vessel hematocrits, the ratio again averages.98 (S.D. + .01) following antecubital vein in-jection and .98 (S.D. ± .02) following pulmonaryartery injection. The chief advantage of thismethod of calculation is that it eliminates theneed for analysis of the injectate and thus reducesa possible source of laboratory error.

Similar reasoning can be applied in determiningthe hematocrit of the "pulmonary" circulation di-rectly from the measured downslopes of the ex-trapolated curves without blood flow calculation.By this method the "pulmonary" hematocrit aver-ages .98 + .06 (S.D.) (Table V).

In drawing conclusions from these data it isnecessary to be aware of certain limitations in-herent in the method used in this study. Vol-umes measured by mean transit times must in-

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(6)

LILIENFIELD ET AL.

TABLE V

"Pulmonary" hematocrit as caeulddirccl from extrapolated red cell and plasma time concentration curveolng pulmonary artery injection

1/Downslope

Red Plasmacells albumin Pulmonary Arterial(Sr) (Sp) Sr hematocrit hematocrit Puim. Hct.

Subject sec. sec. Sp % % Art. Hct.

V. K. 2.4 2.8 .86 39.3 43.0 .91L. J. 2.0 2.3 .87 34.9 38.2 .91M. S. 2.9 2.7 1.07 47.1 45.5 1.04J. M. 2.0 1.8 1.11 45.1 42.5 1.06F. I. 2.7 2.7 1.00 38.2 38.2 1.00J. P. 2.4 2.3 1.04 45.4 44.5 1.02P. R. 1.9 2.1 .90 40.2 42.8 .94

Average 2.33 2.39 .97 .98

S.D. -.06

elude the blood contained in all the vessels fromthe injection site and all possible equitemporalinjection sites to the sampling site and all possibleequitemporal sampling sites. Thus, the hemato-crit measured, especially following peripheral veininjection, is the average hematocrit of blood inthe great vessels, heart, and the pulmonary capil-laries. This amount of large vessel blood wouldbe expected to partially mask any effect on themeasured hematocrit of the blood contained in thepulmonary capillaries. Much of this large vesselblood can be eliminated from the measurement byinjecting the indicators into the pulmonary artery.Though there is the possibility that mixing in thepulmonary artery is incomplete, this probably hasno bearing on the hematocrit results. The albuminand red cells are well mixed before injection andshould therefore have the same opportunities withrespect to their pathways through the lung. In-complete mixing with pulmonary artery blood canonly result in measurement of the hematocrit of aportion, rather than the whole, of the pulmonarycapillary bed. It would seem reasonable, how-ever, that results obtained in a part of the lungwould be representative of its entire capillary bed.

The average volume measured by antecubitalvein injection was 2163 ml. compared to an aver-age of 1252 ml. by pulmonary artery injection(Table II). In spite of this elimination of about900 ml. of large vessel blood the ratios of themean transit times for red cells and plasma re-mained identical (.97 ± .02), as did the calcu-lated hematocrit ratios (.98 ± .02) (Figure 3).Neither of these ratios is statistically different

from unity (P > .05), and their failure to changewith injection site indicates that the circulatingpulmonary hematocrit is not significantly differentfrom the hematocrit of the larger entrance or exitvessels. The tabulated change in ratio of centralhematocrit to large vessel hematocrit with injec-tion site shown in Table II (from .99 ± .04 to.98 + .07) is an artefact introduced by the statisti-cal variations in blood flow measurement. Thishas been eliminated, as explained previously, inthe construction of Figure 3.

These data would indicate, therefore, that inthe pulmonary capillary bed of man no significantdegree of axial streaming of red cells can be dem-onstrated by this method, and that the pulmonarycapillary hematocrit, as measured by mean transittime single circulation techniques, is not signifi-cantly different from the large vessel hematocrit.Similar experiments in this laboratory utilizing thehuman forearm capillary beds have also failedto show evidence of significant red cell streamingin its component organs (9).

If then, as these studies suggest, red cells andplasma have the same relative volume of distribu-tion in a single circulation in the lungs and fore-arm capillary beds as they do in the larger bloodvessels, how can the apparent excess of plasmaalbumin space as measured by total body plasmavolume determinations be explained? Studies ofthe splanchnic area in man in this laboratory (10)and independently by Lathem and Gordon (11)by an equilibration method (12), have shown asplanchnic to large vessel hematocrit ratio also ofabout .91. This in itself would not be sufficient

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HEMATOCRITOF THE LESSER CIRCULATION

50-

"CENTRAL HEMATOCRITVS LG. VESSEL HEMATOCRIT0a CENTRAL HCT.* LG. VESSEL HCT.

ANTE-CUBITAL VEIN INJECTION

AVERAGE RATIO- .98 1 .01 AVERAGE RATIO1.98*.02

FIG. 3. CENTRALHEMATOCRITSDETERMINEDBY MEASUREMENTOF MEANCIRCULATION TIMECOMPAREDWITH LARGEVESSELHEMATOCRITSIN EIGHTEEN STUDIES

to account for the total body plasma albumin ex-

cess. The most likely explanation follows from an

analysis of the methods used in the various studies.Since total body plasma measurements andsplanchnic plasma volume studies require sev-

eral minutes for equilibration, it seems likely thatthere exists a slowly circulating albumin space,

either extravascularly or in intermittently closedcapillaries containing trapped plasma, which equili-brates over several minutes with tagged albumin,and which is not measured by single circulationtechniques. The observations of Rapaport,Kuida, Haynes and Dexter (13) in studying thepulmonary blood volume in dogs by both singlecirculation and equilibration methods would sup-

port this concept.Another possibility to be considered is that

albumin entering a capillary might not diffuse intoa layer of slow moving plasma lining the capillarywall during a single circulation. The rate of mix-ing of entering albumin with this circumferentiallayer of plasma will depend upon the rate of diffu-sion of albumin in flowing plasma. Since albuminis of relatively large molecular size, its rate ofdiffusion is less than that of the smaller crystal-loids and might be sufficiently small to preventcomplete exchange with the circumferential layerof plasma albumin during a single circulation.

Under these circumstances, the method used inthis study would not be expected to measure thevolume of this lining of plasma.

Failure of complete exchange of intravascularalbumin does not seem likely, however, from thefollowing consideration: if there were critical dif-ferences in mixing, due to variations in diffusioncharacteristics of substances of different molecu-lar size, one would expect that small moleculeswould exhibit more complete exchange with thecircumferential plasma layer than larger proteinmolecules. If this were the case the mean circu-lation time of albumin during a single circulationwould be significantly less than that of smallercrystalloids. However, in studies of the centralcirculation the mean transit times of thiocyanateion (14) and ionic Na24 (15) have been found tobe identical with simultaneously injected labelledalbumin and hence must have the same intravascu-lar volume of distribution as the albumin. Itwould seem then to be valid to assume at this timethat, during a single circulation, albumin mixeswith all the plasma contained in a capillary intowhich it enters.

SUMMARYAND CONCLUSION

Red cell and plasma flows, mean circulationtimes, and indicator dilution curve downslopes

I~-

00I.-4

=

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LILIENFIELD ET AL.

were simultaneously but independently measuredin the lesser circulation in normal human subjectsusing Crl1 tagged red cells and I131 tagged albu-min. Hematocrits of the lesser circulation and"pulmonary" capillaries were calculated from thedata and compared to the arterial hematocritmeasured in Wintrobe tubes. The ratio of lessercirculation to large vessel hematocrits averaged.98 ± .02 (S.D.). The results suggest that axialstreaming of red cells in the lung capillaries doesnot occur to any significant extent.

ACKNOWLEDGMENTS

The authors gratefully acknowledge the valuable tech-nical assistance of Miss Jean Pietras, Mrs. Irma Kranzler,and Mrs. Elizabeth Marsden.

REFERENCES

1. Fahraeus, R., The suspension stability of the blood.Physiol. Rev., 1929, 9, 241.

2. Barnes, D. W. H., Loutit, J. F., and Reeve, E. B., Acomparison of estimates of circulating red bloodcell volume given by the Ashby marked red cellmethod and T 1824-hematocrit method in man.Clin. Sc., 1948, 7, 135.

3. Freis, E. D., Stanton, J. R., and Emerson, C. P.,Estimation of relative velocities of plasma and redcells in the circulation of man. Am. J. Physiol.,1949, 157, 153.

4. Lawson, H. C., Overbey, D. T., Moore, J. C., andShadle, 0. W., Mixing of cells, plasma and dyeT-1824 in cardiovascular system of barbitalizeddogs. Am. J. Physiol., 1947, 151, 282.

S. Hamilton, W. F., Moore, J. W., Kinsman, J. M., andSpurling, R. G., Studies on the circulation. IV.Further analysis of injection method, and ofchanges in hemodynamics under physiological andpathological conditions. Am. J. Physiol., 1932, 99,534.

6. Lilienfield, L. S., and Kovach, R. D., Simplified methodfor calculating flow, mean circulation time anddownslope from indicator-dilution curves. Proc.Soc. Exper. Biol. & Med., 1956, 91, 595.

7. Newman, E. V., Merrell, M., Genecin, A., Monge, C.,Milnor, W. R., and McKeever, W. P., The dyedilution method for describing the central circu-lation. Circulation, 1951, 4, 735.

8. Hetzel, P. S., Swan, H. J. C., and Wood, E. H., In-fluence of injection site on arterial dilution curvesof T-1824. J. Applied Physiol., 1954, 7, 66.

9. Lilienfield, L. S., Kovach, R. D., and Freis, E. D., Simi-larity between the large vessel and forearm "capil-lary" hematocrits as determined by the singlecirculation indicator dilution technics. (Abst.)Circulation, 1955, 12, 741.

10. Hershenson, L. M., Marks, P. A., Lilienfield, L. S.,Rodnan, G. P., Kovach, R. D., Ebaugh, F. G., Jr.,and Freis, E. D., Splanchnic hematocrit in man.In preparation.

11. Lathen, W., and Gordon, M. E., The circulatingsplanchnic red blood cell and plasma volumes andthe splanchnic hematocrit in man. (Abst.) Clini-cal Research Proceedings, 1955, 3, 37.

12. Bradley, S. E., Marks, P. A., Reynell, P. C., andMeltzer, J., The circulating splanchnic bloodvolume in dog and man. Tr. A. Am. Physicians,1953, 66, 294.

13. Rapaport, E., Kuida, H., Haynes, F. W., and Dexter,L., The influence of the pulmonary hematocrit onthe determination of the circulating pulmonaryblood volume. (Abst.) Clinical Research Pro-ceedings, 1955, 3, 110.

14. Lilienfield, L. S., Freis, E. D., Partenope, E. A., andMorowitz, H. J., Transcapillary migration of heavywater and thiocyanate ion in the pulmonary circu-lation of normal subjects and patients with con-gestive heart failure. J. Clin. Invest., 1955, 34, 1.

15. Kovach, R. D., Lilienfield, L. S., Hershenson, L., andFreis, E. D., Transcapillary migration of radio-active sodium' through the pulmonary and forearmcapillary beds of man. (Abst.) Circulation, 1955,12, 734.

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