THE HEPATIC CIRCULATION 



'399 



testinal absorption of BSP, though it does occur, does 

 not seem to result in a significant difference between 

 portal venous and arterial concentrations. Whether 

 derived from intestinal contents or from hepatic 

 cells, BSP conjugate displays the same spectral 

 properties as standard BSP, but its extinction coeffi- 

 cient appears to be slightly different ( 1 88). The error 

 so produced also tends to cancel out. A larger error 

 may result from conjugation that occurs elsewhere 

 in the body, as in the kidney ('252). However, BSP 

 conjugate from this source seems to contribute in- 

 significantly to the blood level, even in hepatec- 

 tomized dogs with prolonged maintenance of very 

 high plasma BSP concentrations. BSP conjugate ac- 

 counted at most for 10 per cent (1.0 mg per cent) of 

 the plasma BSP concentration 45 min after adminis- 

 tration, with plasma levels falling from 17 to 10 mg 

 per cent, in two dogs studied by Rosenau and his 

 associates (252). 



The most important drawback in the use of BSP, 

 rose bengal, and indocyanine green for the measure- 

 ment of hepatic blood flow lies in the impossibility 

 of sampling a mixture of all the venous blood draining 

 from the liver. The liver is a large organ in which 

 nonuniform perfusion, inequalities in tissue activity, 

 and heterogeneity of bile formation may be induced 

 at any time by a large number of extraneous factors. 

 Nevertheless, many workers (77, 146, 232, 275) have 

 failed to find any significant difference between con- 

 centrations of BSP in blood taken from different 

 hepatic veins in the same animal, provided peripheral 

 plasma levels are kept constant and comparable. 

 Differences observed by others (49, 118) may be 

 ascribed to changing concentrations or to sampling 

 difficulties. Careful control is especially important 

 during withdrawal of blood through the catheter in 

 an hepatic vein (62, 118, 146, 257). Diaphragmatic 

 movements result in displacement of the tip of the 

 catheter by pressing the liver down and in doing so 

 predispose to retrograde suction of blood from the 

 inferior vena cava. In the dog, contraction of the 

 hepatic venous musculature seems occasionally to 

 block venous outflow from the liver without inter- 

 ference with reflux. Since this phenomenon occurs 

 infrequently and erratically, it is extremely difficult 

 to appraise quantitatively. Edwards' (118) failure to 

 observe it in three experiments is therefore not sur- 

 prising. As he notes, hasty sampling may result in 

 dilution by residual "washout" saline infusion 

 trapped in the catheter and veins. Care must be 

 taken to avoid wedging the catheter deep in the 



hepatic vein in order to avoid any stimulus to hepatic 

 venous contraction or interference with outflow. 



Of special importance is the fact that obstruction by 

 the wedged catheter may affect portal venous inflow 

 preponderantly so that the sample obtained consists 

 largely of blood originating in the hepatic artery. 

 Sapirstein & Reininger (257) have reported values 

 for sodium />-aminohippurate (PAH) concentration 

 in "wedged" hepatic venous samples during mesen- 

 teric venous infusion of PAH that suggest such a 

 possibility. Although their results may be explained 

 by nonuniform distribution of PAH attributable to 

 "streamlining," a recent paper by Brauer et al. (62) 

 brings forward new evidence supporting the idea of 

 interference with portal venous inflow by the catheter. 

 These workers have injected S' i5 -labeled BSP into 

 the portal vein or hepatic artery as a means of dif- 

 ferentiating arterial and venous components in the 

 outflow. With the former, radioactivity remained 

 much lower in the hepatic vein than in the femoral 

 artery, whereas radioactivity rose promptly in the 

 hepatic vein and remained higher than in the femoral 

 artery when BS :i5 P was injected into the hepatic 

 artery. This phenomenon would not affect determina- 

 tion of BSP extraction if BSP were removed to the 

 same extent from hepatic arterial and portal venous 

 inflows. Andrews and his associates (14) have claimed 

 that extraction is in fact more complete when BSP 

 is infused into the hepatic artery than when it is given 

 by the portal vein in perfused canine livers. Other 

 workers (62, 83) have failed to confirm this observa- 

 tion, however, and in a variety of critical studies have 

 found little difference in efficiency of extraction be- 

 tween the two routes. Nevertheless, the uncertainties 

 inherent in hepatic venous sampling call for caution 

 in interpretation and should be acknowledged by 

 referring to the measure as "estimated hepatic blood 

 flow" or EHBF. 



The best evidence that clearance and extraction 

 techniques with constant infusion yield valid estimates 

 of hepatic blood flow has been obtained from simul- 

 taneous measurements by direct methods. Selkurt 

 (264) found that the BSP method overestimated 

 flow by 7.3 per cent on the average when total 

 hepatic venous outflow was measured by collection 

 and reinfused in 274 comparisons in 14 experiments. 

 Similar results have been obtained by Shoemaker 

 (275) and by Drapanas and his associates (114) using 

 other direct methods. Changes in blood flow follow- 

 ing hemorrhage or transfusion were accurately re- 

 flected in values for EHBF. In view of unavoidable 

 trauma and blood loss that would enhance extra- 



