IT SEEMS established in normal man that

Transcription

1 Dilution Curves of Simultaneously Administered I -Human Serum Albumin and Cr 51 - Labeled Erythrocytes in Patients with Various Types of Edema By JOHN TUCKMAN, M.D., AND FRANK A. FINNERTY, JR., M.D. IT SEEMS established in normal man that the direct plasma volume (labeled plasma protein) is greater than the indirect plasma volume (labeled erythrocytes hematocrit) } 2 Simultaneous arterial dilution curves in normal man of I 11 -human serum albumin (HSA) and Cr 51 -labeled red cells (Cr- 51 RBC) performed in this laboratory (fig. 1) demonstrated that: (1) a discrepancy between the apparent direct (I 1I -HSA) and indirect (CR 51 -RBC) plasma volumes became evident with the first appearance of systemic recirculation; and (2) the apparent body/large vessel hematocrit ratio (B/LVH ratio) remained approximately the same during the next several minutes. These data were interpreted to indicate that a significant amount of I 11 -HSA did not escape the intravascular space during the first several minutes post injection, and that the "extra" direct plasma was rapidly equilibrating with respect to albumin. The present communication presents data on arterial and venous dilution curves of simultaneously administered I 11 -HSA and Cr r>1 -RBC in 1 patients with edema of various etiologies- From the Department of Medicine, Georgetown University School of Medicine and the Georgetown Medical Division of the District of Columbia General Hospital, Washington, D. C. Supported by research grants from the American Heart Association; the National Heart Institute (H-2509), U. S. Public Health Service; Ciba Pharmaceuticals, Inc., Summit, New Jersey; and Charles Pfizer & Company, Inc., Brooklyn, New York. Dr. Tuckman is a Postdoctoral Research Fellow, National Heart Institute, TJ. S. Public Health Service. This work was done during Dr. Finnerty's tenure of an Established Investigatorship of the American Heart Association. Eeeeived for publication May 15, Methods The patients were divided into two groups. Group 1 consisted of eight patients with severe edema due to congestive heart failure (table 1). Group 2 consisted of six patients with moderate to severe edema associated with chronic glomerulonephritis (B.J. and I.F.), disseminated lupus erythematosis (P.F.), pre-eelampsia (M.B.), Kimmelstiel-AVilson syndrome (J.AV.), and careinomatosis (R.R.) (table 2). Only one patient (J.W.) had clinical signs of pulmonary edema. The diagnoses of the patients in group 2 were all confirmed by biopsy or postmortem study except for the patient with pre-eclampsia. The subjects were studied in the fasting state, having been confined to bed for at least 2 hours prior to study. Each patient's legs were horizontal, but the upper portions of the body were elevated 0 to 5 degrees to avoid respiratory difficulties. Indicators were injected during a three-second interval into an anteeubital vein through a 20-gauge needle from a calibrated syringe. Samples were collected in tubes containing dried heparin from the femoral artery in 12 procedures and from an anteeubital vein (opposite to that of injection) in 2 procedures. The radioactivity of the samples was determined in a scintillation well counter." Samples and background were counted for periods which gave an accuracy of ± 1 per cent in the sample count rate corrected for background. The dosages of the indicators administered were approximately 0 /ic. I 11 T-HSA and 0 /xc. Cr 51.J Prior to administration, a suspension of the patients' red cells was incubated with the radioactive chromate and washed three times with normal saline. Just prior to injection, I 11 -HSA was added with 1 ml. of the patient's plasma to prevent absorption of I 11 -HSA to the walls of the equipment used during administration and Nuclear Instrument and Chemical Corp., Chicago, Illinois. ie. R. Squibb Co., New York, New York, or Abbott Laboratories, N 1. Chicago, Illinois. {Rachroinate, E. R. Squibb Co., New York, New York. Circulation Research, Volume IX, September 1S61

2 *V,\. = post injection. tb/iyvh ratio = body/large vessel heinatocrits ratio. {End of procedure 0 minutes post injection; although the procedure was not. sufficiently long for construction of phase, phase 2 had obviously ended. Wlien a phase does not begin or end at same time for both indicators, the time at which this calculation has boon made is indicated in parentheses. No distinct phase 1, 2, or final mixing period. Mixing complete at 20 minutes post injection for both indicators. 11 Not including L.W. {}Seo explanation in text. O CURVES 2 arch. Volume IX tn? nber 19 a Group 1 (Congestive Heart Failure Hdeina): ministration of I 1S1 -HSA and Crsl -RBC 1 tn J.P. J.B.} B.L. E.D. W.N. I'"-HSA Cr B1 -RBC L.W.** L.M. M.S. Mean S.B. Indicators I'"-HSA (V'-ftBC ] 1S '-HSA Oi B1 -RBC 1 1! "-HSA Ci^-RBC I""-HSA Cr n -RBC 1"'-HSA Cr- n -RBC HSA (V'-RBC I 1!lt -HSA Cr Bl -RBG I 1S1 -HSA (V'-RBC 1"'-HSA CV'-RBC End min. * 7 o 11 2% S ± ± Phase 2 Per cent disappearance (per hour) S tt 86 ±17 ±21 Final mixing period end min } { 19 ± 8 ±1 end min Table 1 Dilution Characteristics of Labeled Plasma Proteins and Red Cells Obtained by Simultaneous Ad- One min S8 79 "Apparent" plasma volume (ml.) c End phase beginning o cw One min S "Apparent" B/LVH ratiot Two min End phase (7') 0.7 (11') 1.06 (8') beginning (20') 1.01 (0') 0.81 (20') 0.88 (0') 0.96 (') TJ S H "Extrapolated" Volume (ml.) B/LVH ratio ±0.11

3 to Table 2 o Group 2 (Noncongestive Heart Failure Edema): Dilution Characteristics of Labeled Plasma Proteins and Red Cells Obtained by Simultaneous Administration of I 11 -TISA and MCO Cr^'-RBC Subject J.W. P.F. M.B. B.J. :r.p. R.K. Ml'MIl S.D. Diagnosis rciminelstiol- Wilson syndrome Disseminated lupus orytlieniiitosis Pre-ochmpxin Chronic glomerulonephritis Chronic Rloinemlonophrit is Carcinomatosis Indicators I 1 '-HSA Cr cl -RBC I m -HSA Cr Dl -RBC T iai -HSA Cr n -1?BC T'"'-HSA Cr r ' l -RBC I 11 -HSA IV-UBC I 1 " 1 -! ISA iv'-jrbc I 1 '-HSA Cr '-EBC F"-HSA Cr ra -RBC Phtise 2 End min. * 8 11 ±1 ±1 Per cent disappearance (per hour) Final 6** 80 ± ±18 mixing period end min. 9 20' lott 7 ±6 ± end min One min. (P.T.) "Apparent" plasma volume (ml.) Two min End phase beginning c w One min "Apparent*'B/LVH ratiot *P.I. = post injection. tb/lvh ratio = body/large vessel honiatocrits ratio. {When a phase does not begin or end at same time for both indicators, the time at which this calculation has been made is indicated in parentheses,.data are based on venous samples. No distinct phase 2 or final mixing period. Mixing complete at two minutes post injection for r 1 -HSA and 12 minutes for Cr B1 -RBC. **Not including I.F. t tsee explanation in text. Two min End phase t (8') 0.9 (11') beginning (20') 0.9 (11') 1 C 0.80 (50') (50') 0.8 (55') 0.89 "Extrapolated' Volume (ml.) B/LVH ratio ±0.09 a o

4 DILUTION CURVES 1 cts./ml./min. PHASE I I PHASE II I 11 HSA PHASE. iill plasma vol. (ml.) PHASE II FINAL MIXING PERIOD 000- PHASE III I 11 HSA Cr 51 rbc I Cr 51 rbc MINUTES 50 Figure 1 Simultaneous dilution curves of I 11 -HSA and Cr 5 '-RBC using average values of four normal patients, shmving the, four different portions during the first 120 minutes post injection. later during preparation of standards. 5 Hematocrit determinations (including those of the injected solution) were measured in Wintrobe tubes, spun in an International centrifuge having a radius of ±9 cm. from the center of spindle to tip of column of blood, at approximately 2,000 r.p.m. for 0 minutes. A standard correction of 5 per cent for trapped plasma was used, 6 the variations in this correction due to different hematocrits being considered too small for consideration. 7 All patients' hematocrits were performed on arterial samples, except in those two procedures in which the dilution curves were from venous samples. Femoral arterial samples were collected at threesecond intervals following the beginning of the injection of the isotopes in three patients (L M., M.S., J.W.) and approximately as follows in all patients from whom arterial samples were collected : every three seconds between 0 and seconds post injection; then at 15- or 20-second intervals until four minutes post injection; then every minute until minutes post injection; then at 1, 16, and 20 minutes post injection; and, finally, every 5 or minutes until approximately (0 in one procedure) minutes post injection. The venous samples (L.W., I.F.) were collected: one to three times per minute during the first four minutes post injection; then at similar time intervals as above. Apparent plasma and red cell volumes (tables 1 and 2) are defined here as those volumes for a particular time based on the radioactivity in a sample obtained at that time. Therefore: Circulation Research, Volume IX, September MINUTES Figure 2 Simultaneous apparent direct (I 11 -HSA) and indirect (Cr 51 -RBC) plasma volumes based on the average volumes of the same four patients presented in figure 1. the apparent direct plasma volume at time t = counts injected (I 11 -HSA) counts/ml, of plasma at time t the apparent indirect plasma volume at time t = counts injected (Cr 51 -RBC) X 1 hematocrit counts/ml, whole blood at time t ' the apparent red cell volume at time t = counts injected Cr 51 -RBC. counts/ml, of packed red cells at time t The apparent body to large vessel hematocrits ratio (B/LVHR) is here defined at this ratio for a particular time, i.e., apparent red cell volume (time t) apparent red cell volume (time t) + apparent direct plasma volume (time t) arterial or antecubital vein hematocrit Direct and indirect plasma volumes were also obtained by extrapolation of the later disappearance slopes to the time of injection and are indicated in tables 1 and 2. The extrapolated body/large vessel hematocrit ratio was also calculated using these values and are presented in tables 1 and 2. Results In normal man, the arterial dilution curves of both isotopes are similar and can be divided into five parts: (1) initial periodic portion, (2) phase 1, () phase 2, () final mixing period, and (5) phase. The dilution curves of I 11 -HSA and Cr^-RBC in the 1 patients with edema (figs. 2 and ) studied

5 1 TUCKMAN, FINNERTY CONCENTRATION cts./ml. /min. 2 n I J 2 I J i.. PHASE II I 11 Cr 81 HSA PHASE 111 rbc O SO 95 minutes Figure Simultaneous dilution curves of I 1S1 -HSA and Cr 51 -BBC of typical patient with edema due to congestive heart failure. Note that the times for completion of rapid mixing are similar for both isotopes. here are analyzed in similar fashion and compared with those curves from normal patients. Initial Periodic Portion and Phase 1 Arterial samples were collected during the first 0 seconds post injection in only (L.M., M.S., J.M.) of the 1 eases. The delay in the beginning of sampling and the slow circulation time in these patients made it difficult to distinguish between the down slope of the initial periodic portion and phase 1. Phase 2 The next portion of both dilution curves began during the second minute post injection. This phase represented a rapid dilution of the indicators (tables 1 and 2), and disappearance slopes could be approximated. The average times of completion post injection and percentage disappearance per hour (calculated by extrapolating this portion of the curve over a -minute period) were in group 1: I I1 -HSA 7. ±.1 minutes (77 ± 17 per cent), Cr si -RBC.9 ±.2 minutes (86 ± 21 per cent), and in group 2: I 11 -HSA 9.8 ± 1.1 minutes (6 ± per cent), Cr 51 -RBC.6 ± 0.6 minute (80 ± 18 per cent). Final Mixing Period After the rapidly diluting portions of the indicator curves in both groups 1 and 2, there CONCENTRATION CIS. /ml./ min HSA Cr" rbc minutes Figure Simultaneous dilution curves of I 1S1 -HSA and Cr 51 -RBC on patient with edema associated with chronic glomerulonephritis. Note that the rapid mixing time for I 11 -HSA is longer than that for Cr sl -RBC. occurred in some patients (though less frequently than in the normal subjects) a period when there were fluctuations of concentration in radioactivity during which it was difficult to construct a reliable disappearance slope. Since many of the patients did not demonstrate this period, the averages presented below were calculated from the end of the final mixing period or the end of phase 2 when the former period was not present. Case J.B. was not included in these averages. Group 1: I 11 -HSA 1 ± 8 minutes Cr 51 -RBC 19 ± 1 minutes Group 2: I 11 -HSA ± 6 minutes Cr 51 -RBC 7 ± minutes The final part of the curve in both groups 1 and 2 was a gentle I 11 -HSA disappearance slope (fig. ). The average disappearance of I 11 -HSA per hour was: Group 1: 11 per cent (range 0 to 18 per cent) SD ± 6 per cent. Group 2: 12 per cent (range 6 to 17 per cent) SD ± per cent. There was no significant dilution of Cr 1 - RBC during this period. The apparent direct (I 11 -HSA) and indirect (Cr 51 -RBC) plasma volumes as well as the plasma volumes calculated from extrapolation of the last portion (phase ) of the dilution curves to the time of injection are presented in tables 1 and 2. The ratios of apparent and extrapolated body/ large vessel hematocrit are also presented in tables 1 and 2. Circulation Research. Volume IX, September 19B1

6 DILUTION CURVES 15 The extrapolated B/LVH ratios in patients E.D. (congestive heart failure), P.F. (disseminated lupus erythematosis), and M.B. (pre-eclampsia) were above the upper limit presented in most series for normals 1 ' 2 and for patients with congestive heart failure. 8 - That those data are due to individual patient variation ' n and not laboratory error is suggested by studies redone in patients E.D. and M.B. several weeks later when they were clinically dematous. In the repeat studies, the extrapolated B/LVH ratios were 0.98 and 1.02, respective]}'. Discussion Since any discussion of the dilution curves in edematous patients presented here must necessarily center around their similarity to or difference from the curves of normal patients, a review of the data from normal subjects seems in order. In normal man, the oneor two-hour dilution curves of I 11 -HSA and Cr 51 -RBC are similar and can be divided into five parts. Of particular interest are the observations that: (1) I 11 -HSA and Cr 51 -RBC complete the period of rapid mixing (end of phase 2) in the same period of time; (2) a significant difference between the apparent direct and indirect plasma volumes appears with the first evidence of systemic reeireulation; and () the apparent B/LVH ratio remains approximately the same during the entire period of rapid mixing (phases 1 and 2). The latter two observations are in agreement with those obtained by Bauraan et al. 1 " using P' I2 -labeled red cells and I 11 -HSA in humans, and those of the shorter procedures (80 seconds) of Vidt and Saperstein in the dog 1 with T 182 and O 51 -RBC. Previously, we hypothesized that this rapidly equilibrating "extra" direct albumin space is largely intravascular, since, even if an excessively protein-permeable capillary network does exist, the relative slowness of filtration and the slow diffusion of the large albumin molecule 1 would not allow I 11 -HSA equilibration between extra- and intravascular spaces in the required short period of one capillary transit time. Necessarily, also, the Circulation Research, Volume IX, September 61 data are inconsistent with the hypothesis of Smith, Arnold, and Whipple 1 ' 16 that the "extra" direct plasma is located in a stagnant, slowly equilibrating marginal layer of small vessel plasma. This latter conclusion is also supported by recent work of Sliwinski and Lillienfield 17 who, using simultaneous administration of labeled red cells and macroglobulin, demonstrated a significant amount of rapidly equilibrating "extra" direct plasma in the hind limb of the dog. Indeed, the slow diffusion of I 11 -HSA would seem even to argue against significant red-cell streaming (i.e., with a peripheral layer of rapidly equilibrating plasma) in the large majority of small vessels. While it is true that direct observation has shown some small vessels to have axial red-cell streaming, 18 and the experiments of Fahraeus in relatively large straight glass tubes (50 to 00 /x diameter) demonstrate this axial streaming, 1 " many other small vessels 18 - '-" 21 demonstrate now in which only plasnia is present or in which groups of red cells are separated by relatively large areas of plasma. It would seem then that any speculation as to the cause of the discrepancy between direct and indirect plasma volume measurements should certainly consider these latter two observations. The dilution curves in patients with edema associated with congestive heart failure (group 1), when compared to those of normal subjects, show a tendency for prolongation of the periods of rapid (phase 2) and final mixing of both indicators. Slow plasma protein and red-cell mixing to such patients has been reported before by others.' 2-2 Further analysis of the dilution curves indicate that, in six of the eight patients with congestive heart failure, there is no significant loss of I 1I -ILSA from the intravascular compartment during the first several minutes post injection. In these six patients, the time for completion of rapid mixing (end of phase 2) was similar for both isotopes. In four of the six patients (J.P., E.D., W.N., L.M.), the B/LVH ratio during the first minute post injection was approximately the same as this ratio at the end of rapid mixing. In the two

7 16 TUCKMAX, FINNBRTY remaining of these six patients (L.W., M.S.), whereas a large difference existed between the ratio at one minute post injection and that at the end of rapid mixing, there was no significant difference between the two-minute ratio and that at the end of rapid mixing. It is probable that the difference between the first- and second-minute ratios in these two patients was due to slow whole blood intravascular mixing, so that the first-minute B/LVH ratio was less influenced by the lower hematocrit of the small vessels. In patient L.W., the dilution curves were based on venous samples; in patient M.S., mixing was so slow at one minute that I 11 -HSA and Cr 51 - RBG were only 25 and 5 per cent mixed (the extrapolated value at time of injection is used as 0 per cent mixing). On the other hand, in two of the eight patients (J.B., B.L.) with congestive heart failure, there is evidence that the "extra" direct plasma was distributed in both rapidly and slowly equilibrating spaces. In both subjects, the apparent B/LVH ratio at one minute post injection was less than unity, thereby indicating a rapidly equilibrating protein intravascular space. In addition, in both patients the B/LVH ratio during the entire two minutes post injection was appreciably greater than that at the end of the period of rapid mixing (phase 2). This latter difference was not due to slow whole-blood intravascular mixing since the two-minute samples of Cr 51 were well mixed. Is this slowly equilibrating "extra" direct albumin space intra- or extravascularf Unless the disappearance slope of phase is used as an indicator of capillary permeability to protein, the question cannot be answered. In patient B.L., the disappearance slope of phase is flat during 20 to minutes post injection. It might thereby be argued that the capillaries are not excessively permeable to protein, and therefore, the slowly equilibrating space in question is intravascular. Since other elements, such as lymphatic return of indicator, also affect the slope of phase, a discussion of the location of the slowly equilibrating albumin space in patients J.B. and B.L. would seem too speculative. It would seem then that, as hi normal patients, a significant quantity of I m -HSA does not escape the intravascular space during the first several minutes post injection in most of the patients herein studied with edema associated with congestive heart failure. These data support those of Bramkamph and others 2 ' 2r ' who were unable to demonstrate inordinate capillary permeability to protein in congestive heart failure. In analyzing the data from the six patients with edema not associated with congestive heart failure (group 2), definite conclusions cannot be arrived at since the group was small and composed of patients with different diseases. Nevertheless, the results are of interest in that (1) the diseases represented are, except for patient R.R., intimately associated with renal damage, low. serum albumin, and anemia; and (2) several investigators have been unable to demonstrate abnormal capillary permeability to plasma proteins in edema associated with chronic glomerulonephritis and toxemia of pregnancy. 28 In group 2, the time required to complete rapid Cr 51 -RBC mixing (end phase 2) was not longer than in normal subjects. On the other hand, in five of the six patients in this group, I m -HSA took longer than normal, and conspicuously longer than Cr 51 -EBC, to complete the period of rapid mixing. It can also be noted that in these five cases the B/LVH ratios during the entire two minutes post injection were larger than at the end of rapid mixing (phase 2). This slowly equilibrating albumin space was not dependent on slow whole-blood intravaseular mixing, since the Cr 5I -RBG were well mixed at two minutes post injection. As already indicated, it is probably unwise to use the disappearance slope of phase as an indication of capillary permeability, and therefore, unfortunately, one cannot localize from the data presented for group 2, whether the slowly equilibrating "extra" albumin space is intra- or extravascular. It would seem, then, that the indicator-dilution curves of the edematous patients of group 2 differ both from those derived from Circulation Research, Volume IX, September 1961

8 DILUTION CURVES 17 normal patients and most of the edematous subjects with congestive heart failure. The data are consistent with, but do not necessarily suggest, the possibility that increased capillary permeability to protein is present in these types of edema. Summary Detailed indicator-dilution curves of simultaneously administered I 11 -HSA and Cr 51 - RBC in six of eight edematous patients with congestive heart failure demonstrate that, as in normal patients, a significant quantity of I 11 -HSA does not escape the intravascular space during the first several minutes post injection. It would seem, therefore, that capillary permeability to albumin was not an important manifestation in these patients. Detailed indicator-dilution curves in five of six patients with edema not associated with congestive heart failure differ from those derived from normal patients and from the edematous patients with congestive heart failure. These data do not exclude the possibility that capillary permeability to albumin might be a significant concomitant of edema associated with chronic glomerulonephritis, disseminated lupus eiythematosis, toxemia of pregnancy, carcinomatosis, and Kimmelstiel -Wilson syndrome. References 1. GIBSON, J., PEACOCK, W., SELIGMAN, A., AND SACK, T.: Measurement of circulating red cell volume by means of radioactive iron and dye. J. Clin. Invest. 25: 88, GREGERSEN, M. I., AND ROWSON, K. A.: Blood volume. Physiol. Rev. 9: 07, TUCKMAN, J., FINNERTY, F. A., JR., AND BUCHHOLZ, J. H.: Discrepancy between body and venous hematocrits: Dilution curves of simultaneously administered I I1 -HSA and Cr 51 - labeled erythrocytes in man. J. Appl. Physiol. 1: 585, STERLING, K., AND GRAY, S. J.: Determination of circulating red cell volume in man by radioactive Chromium'' 1. J. Clin. Invest. 29: 161, REEVE, E. B., AND PRANKS, J. J.: Errors in plasma volume measurement from absorption losses of albumin I 1 ". Proc. Soc. Exper. Biol. & Med. 9: 299, VASQEUZ, O. N., NEWERLY, K., YALOW, R. S., Circulation Heaearch, Volume IX, September 1961 AND BERSON, S. A.: Determination of trapped plasma in the centrifuged erythrocyte volume of normal human blood with radioiodinated (I 11 ) human serum albumin and radiosodium (Xa 2 ). J. Lab. & Clin. Med. 9: 595, CHAPLIN, H., JR., AND MOLLISON, P. L..: Correction for plasma trapped in the red cell column of the hematocrit. Blood 7: 1227, SCHREIBER, S. S., BAUMAN, A., YALOW, R. S., AND BERSON, S. A.: Blood volume alterations in congestive heart failure. J. Clin. Invest. : 578, SAMET, P., PRITTS, H. W., JR., PISHMAN, A., AND COURNAND, A.: Blood volume in heart disease. Medicine 6: 211, VEREL, D.: Observations on the distribution of plasma and red cells in disease. Clin. Sc. 1: 51, CATON, W. L., ROBY, C. C, REID, D. E., CASWELL, R., MALETSKAS, C. J., FLUHARTY, R. G., AND GIBSON, J. G., II: Circulating red cell volume and body hematoerit in normal pregnancy and the peurperium. Am. J. Obst. & Gynec. 61: 1207, BAUMAN, A., ROTHSCHILD, M. A., YALOW, R. S., AND BERSON, S. A.: Pulmonary circulation and transcapillary exchange of electrolytes. J. Appl. Physiol. 11: 5, VIDT, D., AND SAPERSTEIN, L.: Distribution volumes of T-182 and Chromiums-labeled red cells immediately following intravenous injection. Circulation Research 5: 129, PAPPENHEIMER, J.: Passage of molecules through capillary walls. Physiol. Rev. : 87, SMITH, H. P., ARNOLD, H. R., AND WHIPPLE, G. H.: Blood volume studies: Carbon monoxide method its accuracy and limitations. Am. Physiol. 56: 6, HAHN, P., ROSS, J., BALE, W., BALFOUR, W., AND WHIPPLE, G.: Red cell and plasma volume (circulating and total) as determined by ratio iron and by dye. J. Exper. Med. 75: 221, SLIWINSKI, A. J., AND LILLIENFIELD, L.: Redistribution of plasma and red blood cells in peripheral circulation. Clin. Res. 8: 7, KROGH, A.: Anatomy and Physiology of Capillaries, revised edition. New York, Hafner Publishing Co., FAHRAEUS, R.: Suspension stability of the blood. Physiol. Rev. 9: 21, SANDISON, J. C.: Contraction of blood vessels and observations on the circulation in the transparent chamber in the rabbit's ear. Anat. Rec. 5: 5, ZWEIFACH, B. W., AND METZ, D. B.: Selective distribution of blood through the terminal vascular bed of mesenteric structures and skele-

9 18 TUCKMAN, FINNERTY tal muscle, Second Conference on Microeireulatory Physiology and Pathology. Angiology 6: 282, GIBSON, J. C, AND EVANS, W. A., JR.: Clinical studies of the blood volume: Clinical application of a method employing the azo dye "Evans blue" and the spectrophotometer. J. Clin. Invest. 16: 01, NYLIN, G., AND HEDLUND, S.: Weight of the red blood corpuscles in heart failure determined with labsled erythrocytes during and after decompensation. Am. Heart J. : 770, BRAMKAMPH, E. G.: Protein content of subcutaneous edema fluid in heart disease. J. Clin. Invest. 1:, STEAD, E. A., JR., AND WARREN, J. V.: Protein content of the extra cellular fluid in normal subjects after venous congestion and in patients with cardiac failure, anoxemia and fever. J. Clin. Invest. 29: 28, FISHBERG, A. M.: Hypertension and Nephritis, ed. 5. Philadelphia, Lea & Febiger, 195, p. 75. BOOK REVIEW Arterial Embolism in the Limbs: Clinical Problem and its Anatomical Basis, A. L. Jacobs. Baltimore, Williams & Wilkins Co., 1959, xii pages, illustrated. $8.00. This is the latest and most comprehensive monograph on embolic obstruction of the arteries of the limbs. It is based on the author's own extensive personal experience during a 15-year period. The monograph effectively deals with the clinical, anatomical and pathological aspects of embolism; the final chapter is a summary of the main conclusions. The remarks on therapy are worth repeating: Though the number of successes is not great, embolectomy holds first place in the treatment of embolism of the larger limb arteries. Little benefit can be shown from the various forms of medical treatment in use and some of them may be harmful. Circulation Research, Volume IX, September 1961

10 Dilution Curves of Simultaneously Administered Human Serum Albumin and Cr 51 -Labeled Erythrocytes in Patients with Various Types of Edema JOHN TUCKMAN and FRANK A. FINNERTY, JR. Circ Res. 1961;9:-18 doi:.1161/01.res.9.5. Circulation Research is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 7521 Copyright 1961 American Heart Association, Inc. All rights reserved. Print ISSN: Online ISSN: The online version of this article, along with updated information and services, is located on the World Wide Web at: Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation Research can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: Subscriptions: Information about subscribing to Circulation Research is online at: