642 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



intravenous injection in rats, the venous drainage of 

 K''- is negligible compared with its initial deposition 

 in the organs. Analysis of the radioactivity content of 

 various organs in animals killed 5 to 1200 sec after 

 K^- injection in the femoral vein showed appreciable 

 variation but no definite trend upwards or downwards 

 from 5 to 60 sec. The average values found during 

 the first minute were therefore ascribed to the fraction 

 of the cardiac output distributed to each organ. After 

 3 mill a downward trend was noted in the activity in 

 the kidney. In these studies the activity in the brain 

 was conspicuously low at all times. The e.xtent 

 to which this is due to depression of the cerebral cir- 

 culation by the anesthesia versus inherent peculiari- 

 ties of potassium exchange in the brain is not clear. 



In suljsequent studies the above reasoning has been 

 applied to the determination of the blood flow rates to 

 the hand (57) and the adrenal (58). The same princi- 

 ple, but using Rb*"^, has been used by Goldman & 

 Sapirstein (29) to measure the perfusion rate of the 

 pituitary gland, in which exchange is much more 

 rapid than is true for the brain. 



Although at first glance the above method would 

 seem to be open to the objection that mixing cannot 

 be complete by the time of the first point (5 sec), 

 further reflection shows that longitudinal mixing 

 would l)e unimportant if all tissues had an extraction 

 ratio of 100 per cent. If, however, there is a high 

 venous return of K^'- from the brain (or other organ), 

 this activity is redistributed among the other tissues 

 and the calculated perfusion rates, if expressed as 

 fractions of the cardiac output, will be too high. If 

 more complete data on the potassium exchange in the 



brain are available for the time interval concerned, a 

 correction for cerebral flow would seem to be in order. 



Regional Flow Rates by Tissue Clearance 



Dobson & Warner (22) have injected Xa-^ directly 

 into the artery supplying a limb or tissue, giving that 

 region an initialK' high concentration of activity, 

 and have characterized tlie circulation of the region 

 inxolved by the subsequent rate of disappearance of 

 the tracer. For the human forearm, interpretation of 

 the data is based on a model ha\ing three compart- 

 ments circulated in parallel, the washout curve 

 having three exponential components. Comparison 

 of the washout curves obtained similarly with I''" ion 

 and I '^'-labeled albumin has been u.sed to estimate 

 the relative sizes of the intravascular and extravascu- 

 lar pools in the tissues involved. Conn (17) discusses 

 other aspects of the measurement of regional circula- 

 tion rates by the clearance method. 



SLTMM.^RY 



The elementary mathematical principles applicable 

 to determining regional flow rates by interpretation of 

 the behavior of tracers in steady-state compartmented 

 systems are developed in sufficient detail for use by 

 no\ices in the field. The more complicated systems, 

 particularly nonsteady-state systems, are not treated 

 i)ut are referred or alluded to in the references cited. 

 The analysis discussed is particularly suited to use 

 with radioactive tracers, and some examples of uses 

 of radioisotopic tracers in determining regional flow 

 rates are discussed. 



REFERENCES 



1 . Anger, H. O. and F. T. Upham. In-vivo counting methods 

 in medical research. In: Methods in Medical Research. 

 Chicago: Yr. Bk. Pub., i960, vol. 8, pp. 248-253. 



2. Barker, E. S. and J. K. Clark. Measurement of renal 

 blood flow by application of the Fick principle. In: .\telhods 

 in Medical Research. Chicago: Yr. Bk. Pub., 19H0, \ol. B, 

 pp. 283-292. 



3. Bauer, G. C. H. and R. D. Ray. Kinetics of strontium 

 metabolism in man. J. Bone & .loinl Surg. 40.A: 171 -186, 

 '958. 



4. Beierwaltes, W. H., p. C. Johnson, and A. J. Solari. 

 Clinical Use of Radioisotopes. Philadelphia : Saunders, 1957. 



5. Bergner, P.-E. E. Dynamic aspects of method in tracer 

 kinetics. Exper. Cell Res. 17:328-335, 1959. 



6. Bergner, P.-E. E. On the solution of the compartmenta- 

 lized tracer system. Exper. Cell Res. 20: 579-661, i960. 



7. Berman, M. and R. Schoenfeld. Invariants in experi- 

 mental data on linear kinetics and the formulation of 

 models. J. Appl. Phys. 27: 1361 -1370, 1956. 



8. BERM.'kN, M. and R. Schoenfeld. \ note on unique 

 models in tracer kinetics. Exper. Cell Res. 20: 574-578, i960. 



9. Berman, M., E. Shahn, and M. Weiss. A computer 

 program for the fitting of data to a model. 5th National 

 Biophysics Society Meeting, St. Louis, Feb. 1961. 



10. BiNG, R. J. Determination of coronary blood flow. In: 

 .Methods in Medical Research. Chicago: Yr. Bk. Pub. i960, 

 vol. 8, pp. 269-275. 



1 1. BiNG, R. J., H. K. Hellems, and T. J. Regan. Editorial: 



