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HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



2 4 6 8 10 12 14 16 



FIG. 1 8. Correlation of cardiac output as measured by the 

 Fick procedure and by the injection method. [From Hamilton 

 et d. (66).] 



method, with that mea.sured by the Fick procedure 

 (27, 66, 102, 140). These comparisons show a rather 

 wide scatter, reflecting in part the biological fluctua- 

 tions in cardiac output with the longer duration of 

 Fick respiratory sampling frustrating all attempts at 

 simultaneity, and in part reflecting essential lack of 

 technical precision in both methods. In spite of this 

 scatter there is no significant difference in the average 

 results. This in turn means that whatever fault there 

 may be in the exponential prolongation of the down- 

 slope of the dye curve it is not enough to stultify the 

 final answer (fig. 18). 



The need that the indicator should stay in tlie 

 vascular system is moot. A diffusible substance can 

 leave the circulation in the pulmonary capillaries but, 

 since normally there is very little interstitial fluid for 

 it to enter, it probably is not lost in a very important 

 quantity and much of what diffuses out of the pulmo- 

 nary capillaries may very well wash back into the 

 circulation as the indicator concentration becomes 

 low. With normal lungs the loss is about 10 per cent, 

 but it may be much more than that if there is pulmo- 

 nary edema. Stewart (130), who was the pioneer in 

 this field, used salt solution as did H. CI. Wiggers 

 (145) and White (143). Others have used diffusible 

 dye, thiocyanatc (63), and other substances. Diffusible 

 substances are soon lost from the circulation, and re- 

 circulation is less of a hazard than it is when 

 intravascular substances are used. Moreover, the de- 

 termination can be repeated as many times as is de- 

 sirable with diffusible substances. The fact, however, 

 that the diffusible substance will escape into edem- 

 atous lungs, even though the edema is too little to be 



easily detected, strikes a warning that most workers 

 have heeded by using nondiffusible indicators. 



The technique of measuring the concentration of 

 indicator in the arterial blood has been a very im- 

 portant factor in the development of the method. As 

 indicated above, Stewart ( 1 30) was the first to measure 

 a dilution indicator quantitatively. He set up a length 

 of artery as a part of a Wheatstone bridge so that when 

 the blood in the artery changed its conductivity from 

 the passage of the infu.sed salt .solution an alternating 

 current signaled the event in a telephone receiver. On 

 hearing the signal Stewart diverted a part of the 

 arterial stream into a test tube thus sampling the di- 

 luted blood. The analysis consisted of diluting a sam- 

 ple of normal blood with the salt solution so that it 

 equaled in conductivity the blood drawn during the 

 sound. This would give the concentration of infused 

 solution per liter of blood and the rate of infusion 

 from which the rate of blood flow could easily be cal- 

 culated, provided of course that the basic a.ssumptions 

 that no indicator is lost and none recirculated are 

 granted. 



Workers coming after Stewart, including Hcnriques 

 (75, 76), Bock & Buchholz (8), took timed individual 

 samples which were individually analyzed. 



The advent of the visual colorimeter made it easy 

 to use dyes and measure their concentration in in- 

 dividual plasma samples. The work done in Louis- 

 ville, and already referred to, involved the use of 

 separate samples and the visual colorimeter (62) on 

 brilliant vital red, a dye which attaches to plasma 

 albumin and remains intravascular, and which has 

 the further advantage of not staining a patient an 

 unhealthy bluish tint. In fact, patients think them- 

 selves much improved as a result of the pink color of 

 their skin from the brilliant vital red "treatment." 

 The blue dye, T-1824, which is similarly attached to 

 plasma albumin, is more commonly u.sed now because 

 it absorbs light maximally at (625 m/i) a spectral 

 region to which oxyhemoglobin is transparent. This 

 property makes it measurable in the presence of 

 hemoglobin (hemolysis in separate plasma samples) 

 using filters or a spectrophotometer, or whole blood 

 in a cuvette (see below). 



The fact that 20 to 40 individual timed samples had 

 to be centrifuged, pipetted, and diluted — in some 

 cases with alcohol to eliminate fatty turbidity and 

 adventitious protein bound color — (26), made the 

 method seem tedious to those who had been in the 

 habit of using the direct Fick method. This delayed 

 the clinical use of the method until a less tedious 

 analytical technique had been dex'eloiied. 



