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HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



vein to heart to pulmonary bed to heart to artery to 

 vein. The time at which this sample of blood was 

 obtained (zero time being the instant of intravenous 

 injection) was called the "circulation time." 



The circulation time is the time required for an 

 element of blood to travel some standard distance. 

 Hering did not appreciate the significance of the 

 fact that blood does not circulate with uniform 

 velocity. Nor did he appreciate the significance of 

 the fact that two elements of blood starting simul- 

 taneously from the same cross-sectional plane in a 

 jugular vein may, through ramification of the vas- 

 cular network, take quite different paths of quite 

 different lengths to return to the starting point. The 

 circulation time is therefore a measure of some dis- 

 tance traversed at some velocity. Since neither the 

 distance nor the velocity is known, the circulation 

 time tells nothing about either; it measures only 

 their ratio. If distance happens to be relatively con- 

 stant (and this the experimenter must demonstrate), 

 then changes in circulation time are exactly the 

 reciprocal of changes in velocity. But what velocity 

 is measured? As Hering, and all who followed, used 

 the indicator principle, the circulation time is meas- 

 ured at the threshold of detection of indicator. It is 

 therefore the briefest time interval, sometimes called 

 the "appearance time." The appearance time is that 

 time required by those particles or elements of 

 volume that traveled the shortest route at the highest 

 speed. If all particles travel the same path, appear- 

 ance time is a function only of the highest velocity 

 detectable. The distinction is made between the 

 highest velocity in fact and the highest velocity 

 detectable, because many methods used for this 

 purpose have had poor analytical resolving power so 

 that relatively high concentrations of indicator were 

 required for detection. This means that the circula- 

 tion time is somewhat longer than the appearance 

 time determined by more sensitive techniques. 



Two improvements in Hering's technique are 

 noteworthy, not because they were important in 

 advancing theory but because their antiquity may 

 be humbling to contemporary instrumentalists who 

 appear to have been unaware of their origin. 

 "Vierordt arranged a number of cups on a revolving 

 disc below the vein from which blood was to be taken. 

 In these cups samples of the blood were received, 

 and the rate of rotation of the disc being known, it 

 wras possible to measure the interval between the 

 injection and appearance of the salt with considerable 

 accuracy. Hermann made a further advance by 

 allowing the blood to play upon a revolving drum 



covered with paper soaked in ferric chloride." [The 

 quotes are from Stewart (33).] 



Stewart (31) improved the method further by the 

 introduction of a new technique which permitted 

 measurement of circulation time through organs. A 

 solution of sodium chloride was introduced into a 

 blood vessel supplying an organ. A vessel draining 

 the organ was isolated and placed over two elec- 

 trodes so that the blood vessel formed one arm of a 

 Wheatstone bridge. The galvanometer of the bridge 

 was replaced by a telephone and the bridge balanced 

 to yield minimum noise. When blood, diluted by the 

 injectate, reached the outflow vessel the bridge was 

 unbalanced, an event signaled by the howl of the 

 telephone. The time elapsed between injection and 

 howl was the organ circulation time. For vessels too 

 small to be manipulated over Stewart's electrodes, he 

 substituted for NaCl methylene blue "which at first 

 overpowers the colour of the blood and shows through 

 the walls of the blood vessels" (33). 



For a more detailed historical background see the 

 review by Dow (7). 



Aieasurement of Flow 



It was undoubtedly Stewart's experience with 

 measurement of circulation time which led him to 

 refine the method so that it would yield a measure 

 of blood flow. Stewart (32, 34, 35) allowed a NaCl 

 solution of known composition to run for a known 

 number of seconds through a tube passed into a dog's 

 left ventricle from a carotid artery. A sample of the 

 mixture of blood and salt solution was collected from 

 a femoral artery where its arrival was detected by the 

 telephone howl which signaled a change in electrical 

 resistance. To a blood blank (that is, a sample of 

 blood obtained before injection of NaCl), XaCl solu- 

 tion was added until its conductivity matched that 

 of the arterial sample. This, in effect, was a deter- 

 mination of the concentration of indicator in the 

 arterial sample. The amount of indicator in the 

 injectate and its rate of injection were known. The 

 final concentration of indicator in blood (or, as 

 Stewart viewed it, of blood in indicator) w-as achieved 

 because the injectate was diluted by the cardiac 

 output, that is, the amount, q, of indicator injected 

 over time, s, was carried downstream at a rate which 

 was the product of the cardiac output, F, with which 

 indicator was mixed, and the ultimate concentration 

 of indicator, c, or 



<l/s = FXc (i) 



from which the cardiac output was calculated. 



