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At present the most satisfactory estimates of blood volume are obtained from summing simultaneous measurements ofplasma volume, made by a dye method, and cell volume made by a marked cell method (Reeve, 1948 METHODS GeneralThe best method of injecting exact quantities of solutions and withdrawing blood samples was found to be through a fine polythene catheter passed via an ear vein into the great veins near the heart. The technique of catheterization, which has many applications, is described in an appendix. The catheter was maintained patent by a very slow infusion of heparinized saline. Injected fluids were washed in with a little saline; the first portion of a blood sample containing the saline from the catheter was discarded.All animals were starved for 12-15 hr. before an experiment. A preliminary (blank) blood sample of 4 ml. was withdrawn. The suspension of marked cells and the T 1824 solution were then injected and washed in. About 8 min. later a 4 ml. blood sample was withdrawn, and after this at about * Work undertaken on behalf of the Medical Research Council.

l-Arginine labeled with carbon-14 at the guanido group was injected into rabbits, and the ratio of the rates of entry of radioactivity into the protein and urea was determined. This ratio, multiplied by the rate of arginine utilization in urea synthesis and by the ratio of protein to protein arginine weights, gives the rate of protein synthesis. The method applies to albumin and should apply to any plasma protein synthesized in those liver cells which also synthesize urea.

Rabbit plasma albumin was labelled with 118x, injected intravenously, and measurements were made of the radioactivity in plasma, urine, and feces over many days. In some experiments plasma radioactivity was fractionated into Ira-albumin activity and that of labelled breakdown products. Curves of these radioactivities were compared with corresponding curves predicted by four mathematical models. Each model included a vascular and extravaseular albumin compartment in transfer equilibrium, a radioactive breakdown products compartment, and an excretion compartment; but model A supposed I131-albumin catabolism to occur within the vascular system, model B within the extravascular compartment, model C within both, and model D within a separate compartment receiving albumin for catabolism from the plasma. The experimental data were reasonably well predicted by models A and C. However, model D, though data were insufficient for its complete validation, gave the best predictions and agrees with present knowledge of albumin catabolism.Various methods for calculating the rate of albumin breakdown are discussed. When calculations are based solely on the plasma radioactivity data, identical rates are predicted by models A, C, and D. When, as a valuable independent method, eatabolism is calculated from plasma and excreted radioactivities, an error (ordinarily small) is incurred unless account is taken of the rate of passage of Ira-albumin to the breakdown sites, and of the rate of excretion of the radioactive breakdown products.For the m e a s u r e m e n t of the rates of exchange of a l b u m i n between the plasma and tissue fluids, a n d the rate of b r e a k d o w n of plasma albumin, a first req u i r e m e n t is a satisfactory tracer-labelled albumin. A n u m b e r of labels such as C 1~ (1), N 1~ (2), S 85 (3), and 1 I~ (4), have been used, b u t there has been d o u b t w h e t h e r certain of these tracer-labelled preparations, a n d particularly those incorporating I ~31 (5), behave identically as does the animal's unlabelled

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When the anticoagulant, applied force, time of spinning and form of haematocrit tube are standardized, the haematocrit method gives consistent estimates of the volume of packed cells in a sample of blood. A number of workers have determined the relationship between this volume and the volume estimated by an independent method, and it is agreed that the haematocrit packed cell column contains a small amount of plasma. For the independent method most workers have used one of two types of procedure, which may be termed the indirect and the direct. In the indirect procedure the volume of plasma in a sample of blood is determined. The difference between this volume and the volume of plasma determined by the haematocrit method is the volume of plasma trapped in the haematocrit packed cell column. In the direct procedure the packed cells of the haematocrit are separated from the supernatant plasma and analysed directly for their contained plasma. Table 1 summarizes the results of comparisons made by a number of workers between various forms of the haematocrit method and various forms of the indirect procedure (Section A) and direct procedure (Section B). It is seen that the majority of workers' estimates of trapped plasma, expressed as a percentage of the packed cell column, lie between 3 and 5 %. However, Maizels (1945), using a haematocrit method which appears to have been comparable with that used by the majority of workers, found that only about 2-2 % of the packed cell column was plasma, and Chapin & Ross (1942), using a greater centrifugal force for double the time, found that about 8-5 % of the packed cell column was plasma. McLain & Ruhe (1949), from their results on defibrinated ox blood listed in Table 2, have concluded that many of the independent methods are not sufficiently accurate to determine the proportion of plasma in the packed cell column. It is seen that their independent methods of the indirect type gave * Work undertaken on behalf of the Medical Research Council.

When measurements of plasma volume are made in rabbits with T-1824 and rabbit albumin labeled with I131, the dye value averages 1.09 of the labeled albumin value. This dye value is in error, and the probable cause is loss of a fraction of the dye from the circulation immediately after the dye injection. Comparison of the later rates of loss of T-1824 and I131-albumin from the circulation shows that the dye is lost at nearly double the rate of loss of I131-albumin. T-1824 is thus an unsatisfactory label for rabbit albumin, and cannot be used for measurements of rabbit plasma volume. When Fcells (body hematocrit/venous hematocrit) is measured with P32-labeled cells and I131-albumin the average value in rabbits is 0.895.