568 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



-EJECTIOW— » 



0.3 0.4 0.5 



Ttmc in sacont^s 



0.4 0-5 



n seconds 



FIG. 13. Left ventricular pressure-volume curves through a cardiac cycle in the resting and 

 exercising anesthetized dog. The successive points were calculated from the silhouette of the opacified 

 left ventricular contents visualized cinefluorographically. [From Chapman et al. (13).] 



blood contain.^ 200 ml per liter and venous blood 160 

 ml, each liter of blood would take up 40 ml of oxygen 

 in the lungs and it would require a flow of 6 liters 

 per min to transport the 240 ml of oxygen to the 

 tissues. The relation can be expressed 



F = 



A ~ V 



where F equals the flow per unit time, 0, the ox)gen 

 consumption per unit time, and A and V the oxygen 

 content of arterial and venous lalood, respectively. 

 This same principle is inx'olved if a foreign substance 

 is introduced into the blood stream either by injection 

 or inhalation, or if a substance is removed from (or 

 added to) the blood stream at a known rate by the 

 function of liver or kidneys. The blood flow to the 

 organ is to be found from the relation between the 

 rate of removal or addition and the difference between 

 the amount of the substance in a unit of arterial and 

 venous blood, (^n this basis all the clearance methods 

 described elsehwere in this treatise for measuring 

 renal and hepatic blood flow, foreign gas methods, 

 injection and infusion methods, for measuring the 

 cardiac output or regional blood flow, are essentially 

 dilution methods, the general principle of which was 

 first enunciated, as a specific example, by Adolph 

 Fick in 1870, 



PICK METHOD 



In measurement of i)lood flow through the lungs — 

 which is the cardiac output — it is, of course, necessary 



to measure the oxygen in a fair sample of the venous 

 blood which is about to enter the lungs. Blood from 

 peripheral veins may have more or less oxygen than 

 the average mixture from all parts of the iiody. Blood 

 from the warm skin may be hardly different from 

 arterial blood, whereas that from an active muscle 

 (heart) may be depleted of most of its oxygen. It is 

 necessary, therefore, to get blood from the right 

 heart if one is to measure the pulmonary blood flow- 

 by means of the A-V oxygen difference. 



All of these considerations were taken into account 

 in the masterly and meticulous study of Zuntz & 

 Hagemann (150). Taking advantage of the fact that 

 horse blood coagulates slowly, these investigators 

 inserted a rubber tube into the neighborhood of the 

 right heart via the jugular vein and withdrew mixed 

 venous blood samples. Comparing these with arterial 

 blood as to oxygen and COj content, and measuring 

 the gas exchange, Zuntz and Hagemann calculated 

 the cardiac output of their horses during rest, exercise, 

 and digestion. The results were cumbersomely 

 expressed in five figures. When quantitation was 

 used in these early times it was often overmeticulous. 

 The use of five figures to express results that could 

 be significant only to two figures may have caused a 

 subconscious bias against quantitative biology. 

 Moreover, the results were descriptive rather than 

 analvtical and no general principle as to the regulation 

 of the circulation has been derived from them. 



Interest in the application of this method to the 

 measurement of the cardiac output was suspended 

 until the third decade of the present century. In the 

 I g2o's the method was applied by means of direct 



