574 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



16- 

 14- 

 12 



9'8: 



80 

 7 

 6 

 5 

 4 



30- 



2.0 - 



I 0-H 



9f 

 08- 



7^ 

 0,6|-| 9 

 5+- 

 04 - 



3 - 



02 - 



0.1 



005 



\- 



002 



01 



12 mqs injected 



\ Av Cone 4mg/ L 

 I 12 mq diluted by 3 L 



\ 



in 30 sec 



\ Flow '61/ mm 



\ 

 \ 

 \ 

 \ 



± 



Central Volunne • 



* t CT 



\VICTF=||^ F 



\ 

 \ =25 OIL 



\ '2.5L 

 \ 

 \ 

 \ 

 \ 

 \ 

 \ 

 \ 



24 



30 



36 



42 Sec 



FIG. 1 6. Changes in arterial dye concentration after injection 

 into a vein. Cardiac output is calculated from data given on 

 the figure. [From Hamilton (58).] 



has been widely used for localizing and evaluating 

 congenital cardiac defects. These applications are 

 described in Chapter 14. Its usefulness in detection 

 and evaluation of valvular defects is discussed in 

 Chapter 20, its application to the measurement of 

 regional blood flow in Volume II. The time concen- 

 tration curve resulting from the injection or infusion 

 of indicators is subject to interesting theoretical 

 analysis which is quite acceptable mathematically. 

 This forms the proof of the intuitively acceptable idea 

 that not only can the flow be measured by the knowing 

 use of the method but also the capacity of the bed 

 through which the flow takes place can be estimated 

 with equal accuracy. These considerations are taken 

 up in Chapter 18. 



As a method for measuring the cardiac output the 

 procedure is based on the following considerations. A 

 dve or other indicator which does not diffuse out of 



the circulation is injected into the right heart or a 

 venous tributary and appears in the arterial blood. 

 Here the time course of its concentration may be 

 evaluated by analyzing separate timed samples or by 

 means of various continuous monitoring devices which 

 will be referred to below. The injected substance be- 

 gins to appear after a delay of 6 to 15 sec (appearance 

 time). It then builds up to a peak concentration 

 (build-up time) and rounds off. The descending limb 

 seems to be exponential, i.e., to plot a straight line 

 when log concentration is plotted against time. After 

 the exponential descent has progressed for a time, 

 which deperids upon its injection and sampling sites, 

 and upon the condition of the subject, there is a 

 sudden deviation to the right which marks the be- 

 ginning of recirculation of the indicator. 



The flow (F) is calculated from this time-concen- 

 tration curve by the formula F = 60 I/ct, where / is 

 the amount of indicator injected, c the average con- 

 centration of indicator during its first circulation, and 

 t the time of passage of the dye on its first circulation. 

 Exemplifying numbers are given in figure 16. The 

 problem of separating the dye, which is on its first 

 circulation, is important in establishing both c and t 

 in such a way as to include all the indicator on its 

 first circulation in the calculation and to avoid count- 

 ing any of it twice. We prefer to regard the left heart 

 as a simple reservoir and assume that a volume of 

 blood within it is mixed with the indicator. At first 

 the concentration is built up as more indicator enters 

 than leaves. At the concentration peak, dye is leaving 

 and entering at about the same rate. The entering 

 stream quickly falls off in amount of indicator, and 

 during the downslope very little is entering the left 

 heart [see fig. i 7, (78)]. The concentration of dye in 

 the arterial effluent from the heart becomes a simple 

 washout of the left heart and its exponential nature 

 is thus established. If tiie indicator is washed out of 

 the left ventricle and into the arteries in an exponen- 

 tial manner, i.e., if the amount washed out per unit 

 time is proportional to the concentration in the left 

 heart reservoir, the simple prolongation of the down- 

 slope past the recirculation and on as far as is sig- 

 nificant would enclose an area describing the time 

 concentration relations of all the indicator on its 

 first passage and would include none on its second 

 circulation. 



Some doubt has been expressed (see Chapter 18) 

 that the exponential extrapolation is justified. It is 

 clear from the evidence that indicator passing through 

 straight tubes (118), or a tubular arteriovenous net- 

 work such as the pulmonary vasculature (78), does 



