572 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION 



mean transit time of plasma as compared to the rapid 

 axial stream of cells perfusing small vessels (87). 



The delay of blood (and plasma), in passing 

 through the lungs, makes it impossible to use the lungs 

 as a tonometer for mixed \'enous CO 2 tension even 

 though mixing and bulk diffusion difhculties are 

 eliminated by using alveolar (end expiratory) air 

 samples. There is a constant increase in the A-V differ- 

 ences, as rebreathing time is prolonged, caused at 

 first bv slow mixing, slow diffusion, and slow equilib- 

 rium with artcrialized fluid in the lungs, and later by 

 recirculation of blood which has been exposed to re- 

 breathed pulmonary air. Thus with long rebreathing 

 time and high A-V differences the cardiac output 

 would be calculated as low, and with short re- 

 breathing time the figure would be high. It is small 

 wonder that workers with this method reported \'ari- 

 able results (57). Some believed that the circulation 

 rate was 6 to 8 liters per min, some reported 3 to 5, 

 whereas others reported both (53). Variations in time 

 of exposure of air in the lungs seem to be the principal 

 cause of the variability (5). 



The work of Grollman (53) established in the minds 

 of most physiologists of the 1930's the idea that the 

 cardiac output was near the lower of the limits given 

 above. Following the work of Markoff, Muller and 

 Zuntz and that of Krogh and Lindhard (.see 53), he 

 set about to find the rate of disappearance of a foreign 

 gas from rebreathed air and from this, and the oxygen 

 uptake, to calculate the pulmonary capillary blood 

 flow (cardiac output). 



Grollman used acetylene rather than nitrous oxide 

 as his foreign gas becau.se it was more soluble in blood 

 and because it was more easily analyzed. He was a 

 very industrious worker and got admirably self- 

 consistent results under varying conditions. For the 

 normal cardiac output, the figure was 2.2 ± 0.3 

 liters per min per m- body surface. All figures must 

 abide within these Procrustean limits in order to be 

 acceptable at this time. Indeed, the acetylene method 

 gave figures that agreed with the direct Fick procedure 

 in his hands (4). 



We know now as a result of many determinations of 

 the cardiac output by the direct Fick method, as per- 

 formed by Cournand, Richards, and their followers 

 (see above), that the average basal cardiac output in 

 man is 3.3 liters per min per m- instead of 2.2. The 

 evidence is overwhelming that the larger figure is 

 correct, for not only has it been measured many times 

 by the direct Fick method but also figures derived 

 from the injection method are in agreement (.see be- 

 low). Moreover, if we summate blood flow as meas- 



ured independently through the liver, kidney, heart, 

 brain limbs, and so on, we arrive at a figure that the 

 aggregate flow must be of the larger rather than the 

 smaller order of magnitude (57). 



The reason for the discrepancy is not far to seek. 

 Grollman rebreathed his gas 18 to 30 sec under the 

 impression that the complete circulation time was of 

 this order. This was supported by the fact that the 

 calculation of cardiac output was the same, whether 

 the rebreathing was carried on for 18 or 30 sec. Un- 

 fortunately, these times bracket the second rather 

 than the first circulation, so the measurements could 

 be too low without disagreeing. 



E\idence that the total circulation time is of the 

 order of 10 to 18 sec, with a mean at about 15 sec, is 

 to be had from dye injection (69). Moreover, 

 Grollman himself concedes that acetylene returns in 

 appreciable quantities to the right heart in samples 

 taken between 1 3 and 20 sec after rebreathing started. 

 This is congruent with the experiments of Gladstone 

 (47) and with those of Hamilton et al. (69) and of 

 Werko et al. (139), all of which go to show that, by 

 hindering the entrance of acetylene into the blood and 

 by raising the acetylene concentration of the second 

 sample more than the first, thus changing the slope of 

 acetylene disappearance, the Grollman method gives 

 too low a figure for the cardiac output. 



Recently G.ander & Forster (12) have called atten- 

 tion to another error in the Grollman method. In 

 contrast to CO2, which in the absence of carbonic 

 anhydrase in pulmonary tissue and fluids combines 

 slowly, acetylene and nitrous oxide dissoKe instan- 

 taneously in these fluids. This extends the effective 

 pulmonary volume for this gas by about 10 per cent, 

 which would lead to an underestimate of capillary 

 blood flow bv the same amount. These authors mixed 

 about 15 per cent helium into their breath-holding 

 mixture. This gas is quite insoluble and serves as a 

 landmark by which changes in acetslene or nitrous 

 oxide concentration due to bad mixing can be sepa- 

 rated from changes due to solution in the pulmonary 

 capillary stream. By reducing the time of breath 

 holding and controlling mixing, and the effective 

 lung volume, these authors seem to ha\e developed a 

 technique by which the foreign gas method can be 

 used to measure the cardiac output. 



The use of a foreign gas (nitrous oxide) also lends 

 itself to measuring the cardiac output instantaneously 

 from beat to beat. This type of measurement has cer- 

 tain decided advantages over other dilution methods 

 in which the subject must be in a steady state during 

 the time of the sampling (see above). Exploitation of 



