I J.I l_> 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



mining the fractional clearance. Studies of BSP 

 disappearance and of I 131 rose bengal accumulation 

 in the liver indicate the possibility of reflux, of inter- 

 play between coupled reservoirs and transfer systems, 

 and of secondary derangements (e.g., saturation and 

 competition) that may lead to error (45, 122, 177, 

 212, 312). 



Dilution techniques. A third indirect approach to 

 estimation of hepatic (or splanchnic) blood flow 

 depends upon measurement of the dilution of a known 

 quantity of some tracer within the hepatic circulation 

 over an accurately measured time period. In essence, 

 these procedures are adaptations of the Hamilton- 

 Stewart method for the measurement of cardiac 

 output and the Kety-Schmidt method for cerebral 

 blood flow. For the first, which has been developed 

 by Reichman and his associates (239), I 131 -labeled 

 human serum albumin (HSA) is injected into the 

 spleen and the concentration curve followed either 

 a) over the liver by external counting with approxi- 

 mate correction for background, or b) in hepatic 

 venous outflow collected continuously at a constant 

 rate with sampling at regular intervals. Analysis of 

 the hepatic venous radioactivity curve (as in the 

 analysis of pulmonary arterial concentrations for 

 determination of cardiac output by the "dye method") 

 yields a value for the average hepatic venous activity- 

 resulting from dilution of the injectate by splanchnic 

 blood flow during the time chosen. The tracer in- 

 jected into the spleen appears to travel as a compact 

 "bolus" in the splenic venous blood though a frac- 

 tion (significant in 20 % of human subjects) may be 

 left behind in the subcapsular tissues. Delayed entry 

 into the splanchnic bed with "trailing" may result 

 from slow uneven injection. The amount actually 

 injected and diluted within the hepatic blood flow 

 can be computed as the product of the radioactivity 

 in the peripheral blood at equilibrium (taken at 10 

 min after injection) and the total blood volume deter- 

 mined separately. This quantity divided by the cal- 

 culated "average hepatic venous radioactivity" 

 yields a value for the total splanchnic outflow during 

 the period of analysis. Uncertainties arising from re- 

 circulation, nonuniform mixing, determination of the 

 quantity of I m -HSA injected, and possible pooling, 

 together with the difficulties involved in intrasplenic 

 injection, limit the usefulness of this method. A similar 

 procedure has yielded satisfactory results in the dog 

 with injection of iodinated albumin and Cr 5J (labeled 

 erythrocytes) into the portal vein (278). 



Application of the Kety-Schmidt technique has 

 been suggested by a number of students (176, 288). 



The average arterial-hepatic venous concentration 

 difference during equilibration following the intra- 

 venous administration of substances freely diffusible 

 throughout the liver and splanchnic bed, such as 

 radioactive krypton, water labeled with deuterium or 

 tritium, or 4-amino antipyrine, may be divided into 

 the average hepatic venous concentration at equilib- 

 rium to obtain a value for splanchnic blood flow per 

 unit mass of splanchnic tissue. Sapirstein (256) claims 

 that the distribution within the body of such uni- 

 formly diffusible tracers shortly after injection is 

 determined by the distribution of cardiac output and 

 thus indicative of local flow as a fraction of output. 

 According to this view, if radioactive potassium 

 chloride is given to an experimental animal and 

 allowed sufficient time to pass through the heart and 

 lungs to the tissues of the body, and if the animal is 

 killed before appreciable venous drainage and re- 

 circulation have occurred, the K. 4 - content of the 

 various organs can be used to evaluate the pattern 

 of flow distribution. Periods of time ranging from 5 to 

 60 sec before death in the rat or 20 to 120 sec in the 

 dog do not appear to affect the results (except for the 

 brain), presumably because venous K 4 - content is 

 much smaller than the arterial levels during these 

 periods and because recirculation does not begin to 

 contribute for about 30 sec. Although the drawbacks 

 of such a procedure are obvious, interesting and help- 

 ful information may be obtainable by this means 

 alone. 



SPLANCHNIC BLOOD VOLUME AND TRANSIT TIME. The 



volume of blood within the splanchnic bed and the 

 mean splanchnic circulation time may also be meas- 

 ured by an adaptation of the dilution methods (50, 

 94). Comparison and careful timing of the moment- 

 to-moment changes in arterial and hepatic venous 

 concentrations during the period of equilibration 

 following injection of some substance which is con- 

 fined to the vascular bed, such as I 131 HSA, affords a 

 measure of both the total quantity of tracer distributed 

 within the splanchnic bed at equilibrium and the 

 time required for passage from artery to the point of 

 venous sampling. Thus the amount of tracer entering 

 the splanchnic bed between its first appearance in the 

 arterial blood (sampled from a brachial or femoral 

 artery) and the point of equilibrium (defined as 

 agreement between arterial and venous concentra- 

 tions within the limits of analytical error over a 

 period of 30 sec or longer) is equal to the product of 

 the total splanchnic blood flow and the average 

 arterial radioactivity (.7) during that period (/,,, in 



