Regional Lymph Flow in Unanesthetized Rabbits

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INTRODUCTION
In most tissues there is a net filtration of fluid from the capillaries 31-12 a draicage of tissue fluid through the lymph vessels. Cannulation experiments have shown that the lymph flow varies greatly with the activity of the tissue and that elevated venous pressure increases the lymph flow markedly. Plasma protein concentrations seem to vary inversely with the lymph flow (1).
It is often difficult to delimit the region drained by a cannulated lymph vessel and to collect lymph without anesthesia. As a consequence no data seem to exist for lymph production/g tissue in unanesthetized and unrestrained animals. Also few studies have been made on the composition of lymph from well-defined regions under such conditions. The purpose of the present communication is to report approximate values for lymph flow rates in a number of tissues and normal plasma protein concentration in lymph in unanesthetized rabbits. An indirect procedure was used to determine flow rates and these were compared with values for plasma flow obtained under similar conditions (2) in order to obtain figures for the net fluid ' filtration fraction in different vascular beds.

Theory
It has long been suspected that under normal conditions plasma proteins passing out of the blood vessels return to the general circulation mainly via the lymph vessels. In a recent study (2) strong support for this hypothesis was found both for albumin renal cortex, stomach wall, skeletal muscle and gall bladder. In some orgaas, however, namely the heart, choroid plexus, lung and small intestine, some albumin also seemed to be eliminated with the blood, some of the molecules returning by diffusion or some other mechanism. and for IgG in an number of tissues -Both albumin and IgG seemed to enter the lymph vessels in a bulk flow of tissue fluid. Experiments with direct collection of tissue fluid and lymph support this notion ( 3 ) .
If IgG is leaving a tissue o n l y by bulk flow of tissue fluid into the lymph capillaries, the rate of elimination can be calculated as where L is the rate of lymph flow and Ctf is the concentration of the substance in the lymph,Elimination can also be calculated a s where k tissue fluid in which the IgG is distributed.
is the turnover rate constant of IgG and Vtf the volume of the IgG Thus : From previous studies (2) data were available for k and also for the apparent volumes of the plasma-equivalent spaces of albumin intravascular plasma volumes. In the present experiments estimates were obtained for the distribution volumes of 22Na and 51Cr EDTA.For some tissues the latter values could be used as estimates of the extracellular volume. These volumes minus the intravascular plasma volumes represent the volumes of the tissue fluids. It was assumed then that the extrzvascular proteins were distributed within these volumes. This is an overestimate of the true volume of distribution of the proteins but the error was assumed to be moderate. The reason why protein distribution volumes can be expected to be smaller than I & and IgG and the those for low molecular weight such as collagen and glucoseaminoglycans large molecules ( 4 ) .
substances is that connective tissue components tend to cause a steric exclusion of Experiments On the day before the radioactive isotope experiment the animals were anesthetized with pentobarbital sodium and a marginal ear vein and a femoral artery were cannulated with polyethylene tubes for injections and blood sampling, respectively . The plasma-equivalent 51Cr EDTA space in Ul/g tissue was determined by dividing the radioactivity per g tissue sample with that per samples were taken from

1.
On the next day 51Cr EDTA (Hoechst) was injected i.v. in different doses rapidly by an overdose of pentobarbital sodium followed as ~1 plasma. Four each tissue.

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jected in different doses in such a way that the plasma concentration rose for 4 h and then remained stable for another 2 h. The plasma-equivalent 22Na spaces were determined analogously to the 51Cr EDTA spaces.
On the day after the cannulation 22Na (AB Atomenerg?, Studsvik) was in-

RESULTS
The 22Na spaces in most tissues investigated were larger than the 51Cr EDTA spaces and in many tissues the 1 and 2 hour spaces for 51Cr EDTA were very similar ( Table 1 ) . I n the liver and kidney the 51Cr EDTA spaces were significantly higher than the 22Na spaces, and in the brain and gall bladder wall the 51Cr EDTA space was still increasing even after 1 h.

DISCUSS ION
The observation that in the brain the 51Cr-EDTA space was still increasing even after one hour of a steady concentration in the plasma indicates that this substance has a very low turnover rate in the icterstitial space of the brain. For sodium the space was much larger. I n the liver the 51Cr-EDTA space was larger thar, the sodium space, indicating accumulaticn of 51Cr-EDTA or    suggest that the effective mean hydrostatic capillary pressure was close to the isogravimetric value, differing from that value by less than 2 -3 mm Hg.
Heart muscle  . In large pores in the capillary wall there will then tend to restricted to capillaries with continuous blood flow (6). 2 An estimate of 75 cm /g has been reported for the capillary surface in vasodilated skeletal muscle, and of 80 c m ' l g for heart muscle (8). These values and the present data indicate that net filtration per unit capillary surface in 2 the heart is about 9 pl/min/m2 and in skeletal muscle 16 pl/min/m . These values can be compared to the turnover rates for albumin and IgG (2).  Table 2 indicate fivefold differences between the tissues investigated, from 0.17%/min in skeletal muscle to O.a%/min in the small intestinethe values for the stomach, lung and heart muscle ranging in between.
is a measure of the turnover of tissue fluid by net IgG One important,sometimes overlooked consequence of the low turnover of macromolecules in the interstitial tissue fluid is that a change in transcapillary movements of large molecules only has its full effects on the composition of lymph many hours laterfor some tissues, such as skin and skeletal muscle, it may theoretically take days to reach full steady state. For such tissues one can never expect the composition of lymph to reflect anything but a complex function of the macromolecular efflux over a period of time preceding the collection time by many hours and a plasma-tissue fluid balance with respect to water and low molecular weight substances at another time.