648 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



proposed an indirect procedure, whereby valvular 

 insufficiency could be evaluated from ordinary indica- 

 tor dilution curves. By this technique the indicator 

 was injected in a peripheral vein and blood collected 

 in a peripheral artery. This method is based on the 

 supposed invariance in the form of normal dilution 

 curves. When mitral insufficiency was produced, the 

 shape of the curve was altered with inore rapid ap- 

 pearance time, lower peak concentration, and de- 

 crease of the terminal slope in proportion to the 

 amount of insufficiency. 



Figure i shows indicator dilution curves ob- 

 tained by injecting I '^'-tagged human serum albumin 

 into the left atrium of a patient with pure mitral 

 stenosis (MS) and of one with combined mitral 

 stenosis and insufficiency (M.S -|- MI). The effect of 

 regurgitation is a summation of all regurgitant flows 

 between injection and sampling sites. It should be 

 noted that the curve will be flatter and more difficult 

 to evaluate if the injection site is on the right side of 

 the pulmonary circulation or even more peripherally 

 as originally suggested. Korner and Shillingford, in 

 their attempts to quantitate valvular insufticiency 

 from dilution curves, also recognized the necessity 

 of correcting for the effects of cardiac output and 

 blood volume. They attempted to eliminate these 

 effects by comparing the measured disappearance 

 slope of the curve and the degree of dispersion or vari- 

 ance of the curve with the expected values calculated 

 from equations relating these parameters to the car- 

 diac output and "central" blood volume of normal 

 individuals. Their results showed a good discriinina- 

 tion between valvular regurgitation and stenosis. 

 Marshall et al. (142) used the method of Korner and 

 Shillingford in i 1 healthy volunteers and 30 patients 

 with disease of the mitral valve, and showed that there 

 was a significant correlation with the degree of re- 

 gurgitation. However, a considerable overlap between 

 results in normals and in patients with stenosis and 

 regurgitation limits the value of the method. 



Eich and co-workers (57) studied the problem of 

 estimation of valvular regurgitation by dye dilution 

 in 15 dogs, where the technique was applied before 

 and after the creation of mitral regurgitation. The 

 range of regurgitant flow was 20 to 38 per cent of the 

 cardiac output. With a control determination even 

 small amounts of regurgitation could be detected but 

 not cjuantified. Without a control dilution curve 

 (with no leak introduced), no calculation applied to 

 the curve would separate the states without, from those 

 with, a leak. The authors concluded that the reasons 



50,000 r 



T3 

 O 

 O 



o 



M5 

 CO 2 5 



CV 054 

 'Aobs 9 9 



'/gPred II 4 



28 L/mJn 

 C 87L 

 31 9 sec 



138 sec 



37 L /mm 



10,000 - 



6 5,000 



c 



o 

 o 



1,000 



20 30 40 



Seconds 



FIG. I. Indicator dilution curves obtained by injecting 

 I'^'-tagged human serum albumin into left atrium in a case of 

 pure mitral stenosis (MS) and combined mitral insufficiency 

 and stenosis (MI + MS). [From Novack & Schlant (154).] 



for this wide overlap are variations in volume, mixing, 

 and washout, which cannot be asses.sed at present. 



The deformation of the peripheral indicator dilu- 

 tion curve in mitral insufficiency has a complex 

 mechanism. It is a consequence not only of the size 

 of the altered left atrial and ventricular mixing vol- 

 umes produced by the backflow, but also of changes 

 in pulmonary blood volume and total blood flow. 

 Model experiments and studies in dogs with acutely 

 induced mitral insufticiency have demonstrated the 

 inaccuracy of the indirect indicator dilution method 

 for the detection of regurgitation as long as the blood 

 flow and volume are unaltered. Hoffman & Rowe 

 (104) especially have studied the behavior of indicator 

 dilution curves in circulation models and have 

 stressed the importance of chamber \olume and blood 

 flow. The most complete mathematical analysis 

 based on logical statistical movement of indicator in a 

 model system has recently been developed by New- 

 man and his group (62, 63, 123, 124, 145). This 

 analysis indicates that the shape of model indicator 

 dilution cur\es is completeh' dependent on blood flow 

 and the mixing \olumes of ventricle and atrium. The 

 results of these analyses compare well with earlier con- 



