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Effect of Heart Rate on Aortic Insufficiency as Measured by a Dye-Dilution Technique By HOMER K. WARNER, M.D., P H . D . , AND ALAN F. TORONTO, M.D. T Downloaded from http://circres.ahajournals.org/ by guest on July 31, 2017 areas under the two dye curves). Positioning of the catheter tip at the point of origin of the left subclavian artery from the aorta was accomplished in this way. An x-ray was then taken to confirm this position. The catheter was then withdrawn through the femoral needle in 2-em. steps and an injection made after each withdrawal. These injections were made over the last 0.1 second of systole and the first 0.1 second of diastole. In this way, the point was located at which dye injection first failed to result in the appearance of any dye at the left radial sampling site on the first circulation. The distance down the aorta to this point from the point of origin of the left subclavian artery represents the distance over which backflow travels during a single diastole. This backflow distance (BFD) is the fundamental measurement obtained. A number six Cournand catheter was advanced from the left antecubital vein through the right heart and into the pulmonary artery, and through it dye was injected for measurement of cardiac output. A second venous catheter was advanced from the right antecubital vein into the right atrium in such a way that its natural curvature held its tip against the lateral wall of the atrium. On the tip of this catheter was a smooth piece of solder connected to a fine insulated wire which traversed the lumen of the catheter. A 2 volt-1 millisecond square wave applied to this electrode and to an indifferent electrode on the chest wall (fig. 1) resulted in atrial contraction. This technique made it possible to increase the subject'." heart rate. Measurements of backflow distance were made in each of three patients at two heart rates. Results Data obtained from the three subjects are shown in table 1. Net cardiac output and backflow distance per stroke were measured in each of the subjects at two heart rates. The slow heart rate in each instance is the subject's own sinus rate. In subjects (C.H.) and (F.T.) cardiac output increased at the faster rate. In all three subjects, backflow distance per stroke decreased at the fast heart rate to less than one-half the distance measured at the slower rate. The product of backflow distance and heart HE PURPOSE of this paper is to present data obtained on three young adults with aortic insufficiency in whom aortic backflow was estimated b}r a dye-dilution method at two different heart rates, and to consider these results in the light of calculations based on a theoretical analysis of the hemodynamie factors involved. Methods The basic technique employed for the quantitation of aortic insufficiency was described in a previous publication.1 Certain modifications of this technique were used in the experiments here presented. A Peterson-type arterial catheter was introduced into the right femoral artery through a thin-walled, 18-gauge needle and advanced up the aorta until its tip lay near the origin of the left subclavian artery. This catheter was used for delivering a small slug of dye (indoeyanine green)* into the aorta. The distribution of the injected dye between the left subelavian artery and the descending aorta following each injection was determined by recording dye concentration continuously in the left radial and the left femoral artery blood. The dye was injected through the arterial catheter using a pneumatic injection device triggered from the R wave of the electrocardiogram as described previously. This allowed injection of dye over any interval of the cardiac cycle. Dye was initially injected during the first 0.1 second following the R wave. If the catheter had been advanced too far, its tip would enter the left subclavian artery and most of the dye would appear in the first circulation at the left radial sampling site. Then as the catheter tip was withdrawn and subsequent early systolic injections made, a point could be found where dye was distributed equally to both the left radial and left femoral sampling sites (as indicated by equal From the Departments of Physiology, University of Utah and Latter-day Saints Hospital, Salt Lake City, Utah. Supported in part by grants-in-aid from the American Heart Association. Dr. Warner is an Established Investigator, American Heart Association. Keceived for publication November 14, 1960. *Indocyanine green was generously supplied by Hynson, Westcott, and Dunning, Baltimore, Maryland. Circulation Research. Volume IX, March 1961 413 WARNER, TORONTO 414 DATA FROM r - NORMAL MEN for HR55 to 130/min. 0.9 LJJ ° 0.8 I 0.7 - *\ ° 0.6 UJ g ^ 0.4 o z 0.3 — o s > HR>0.lt """"*—V—i. * ' I 0.2 E z. d f in *v _ 0.5 52 IE -0.18 r cr. ^<. • / . 0.1 1 ° 40 1 1 1 1 1 1 1 1 1 50 60 70 80 90 100 HO 120 130 140 150 HEART RATE (mirC1) Downloaded from http://circres.ahajournals.org/ by guest on July 31, 2017 Figure 2 A plot of the duration of systole (Ts) and the duration, of diastole (Td) as a function of heart rate. Figure 1 The white arrow points to the tip of the stimulating catheter in the right atrium. The black arrow points to the tip of the arterial catheter in the descending thoracic aorta. The other catheter is curled in the pulmonary artery. rate is the average backflow (BF) over the whole heart cycle divided by the cross-sectional area (A) of the aorta. Assuming that this area does not change with heart rate, the ratio of aortic backflow per unit time at the slow heart rate to that at the faster heart rate may be calculated. These ratios were 1.61, 1.75, and 1.71. If the descending aorta contributes a constant fraction to the total baekflow across the aortic valve, these measurements of backflow in the descending aorta are an accurate index to the total baekflow across the aortic valve. Theoretical Analysis The significance of these observations may become evident through an analysis of the heinodynamie factors involved. Since aortic backflow occurs only during diastole, the baekflow per minute will depend upon the fraction of each cycle occupied by diastole. As is well known, increasing heart rate results in a much greater decrease in the duration of diastole than in the duration of systole (fig. 2). The effect of heart rate on aortic insufficiency, however, will depend not only on the duration of diastole, but also upon the time-course of backflow during diastole; that is, theflowcontour. Four cases will be considered. Case l Let us first consider the rather unrealistic but easy-to-analyze case in which backflow (f) is proportional to mean aortic pressure during diastole (Pd)- This is expressed as bf = P d , (1) where (b) is a constant. The average backflow over the whole cycle (BF) in this case will he given by " Td (2) BF= b To where (Td) and (Tc) are the duration of diastole and total cycle respectively. Under these conditions, the average backflow over the whole cycle is proportional to the ratio T<i/T0 (fig. 3). Backflow at a heart rate of 70 per minute would be 1.32 times the backflow at a heart rate of 120 per minute. Thus, this model fails to account for our observed ratios which were 1.6 or greater. Case 2 Xext we consider the ease in which backflow during diastole is proportional to the inCirculation Research, Volume IX, March 1961 AORTIC INSUFFICIENCY 415 u, 08 1.4 " 07 o ,. 06 o 1.3 1.2 I " l! o I.I ' * / T e ' 0.87 -.003 HR CM 0.4 uT 1.0 (0>50< HR<I3O s 10J •0.9 0.8 I 0.2 30 0.7 40 50 60 70 80 90 100 110 120 130 HEART RATE (mirC1) Downloaded from http://circres.ahajournals.org/ by guest on July 31, 2017 Figure 3 A plot of the fraction of the total heart cycle occupied by diastole as a function of heart rate based on the equations shown in figure 2. stantaneous aortic pressure, P ( t ) - This is expressed as bf = P( t ) , (3) where (b) is a constant. From recording of aortic pressure, it can be readily shoAvn that to a good approximation P ( t ) = P o e- kt (4) describes the time-course of pressure during diastole. Here, (P o ) is the pressure in the aorta at the onset of diastole and (k) is a constant; (k) will depend upon the resistance to backflow across the aortic valve, the systemic arterial resistance to forward flow, and the distensibility of the aorta. By combining equations (3) and (4), integrating over the duration of diastole, and multiplying by the heart rate (HR), the average rate of backflow over the whole cycle (BF) is obtained. This is given by where (HR) is the heart rate and (Td) is the duration of diastole at that heart rate. Examination of figure 4 shows that in the limit as (k) becomes 0 the ratio of backflow at a heart rate of 70 to backflow at heart rate 120 becomes 1.32 as in the case just discussed, and that this ratio progressively decreases with increasing values of (k). Since (k) was found 0.6 0.5 2 3 K (sec"1) Figure 4 A plot based on calculations using equation (5) of the effect of (k) on the ratio of backflow at a heart rate of 70 to backflow at a heart rate of 120 beats per minute. from examination of recordings of aortic pressure to vary from 0.7 to 2 per second, it can be seen that this model fails by an even wider margin to explain the observed effects of heart rate on aortic backflow. Case 3 In this case, the fact is recognized that the column of blood in the aorta has inertia which will limit the rate at which a new level of backflow can be achieved. A term to account for this is included in a ctf — kt (6) The coefficient (a) is a measure of the inertia of the column of blood which must reverse its flow at the onset of diastole and its units will be mass divided by cross-sectional area squared. The contour of the diastolic backflow curve predicted by solving this equation on an analogue computer is shown in figure 5 for three values of (a) where (a) is expressed in units of mm. Hg sec.2 cm."3. The analytical expression for average backflow over the whole cycle i a this case is given by (7) Circulation Research, Volume IX, March 1961 WARNER, TORONTO 416 CASE-4 TIME SFTER ONSET OF DIASTOLE DISTRIBUTION OF DYE INFLOW STREAM Q=0 0 1 Seconds 0 2 Seconds a-0.02 0 3 Seconds OA Seconds 0 5 Seconds Figure 6 A diagrammatic representation of the effect of development of laminar flow on the distribution of dye in the aorta- at various times during diastole. 0=0.1 Downloaded from http://circres.ahajournals.org/ by guest on July 31, 2017 Time marks = O.I Sec. Figure 5 Analogue computer solutions of equation (6) predicting the time-course of diastolic backfloiv in the aorta for three values of the coefficient (a). This expression is obtained by integrating equation (6) twice and multiplying by heart rate. Solutions of this equation using data obtained from patient C.H. are shown in table 2. Only when (a) is large (0.1 mm. Hg see.-' cm."3) does this model predict a ratio which approaches the value obtained experimentally. Direct measurement of the time-course of backflow in the ascending aorta in patients with aortic insufficiency, through the use of flowmeters at the time of surgery, would make it possible to cheek on the validity of such a value for (a) by comparing the predicted flow curves shown in figure 5 with the flow curve actually recorded. Unless the recorded back- flow curves resemble the curve predicted by equation (6), with (a) equal to 0.1, another explanation for the results here presented must be sought. In the three analyses so far considered, the pressure on the left ventricular side of the aortic valve during diastole was ignored, since left ventricular pressure was not measured in these experiments. The fact that left ventricular pressure certainly rises during the course of diastole would make the discrepancy between measured change in backflow with change in heart rate and that predicted by any of these models even more pronounced. Case 4 Finally, we consider the possibility that thp proportionality constant which relates backflow distance traveled by the dye to backflow volume may be dependent on heart rate. If flow were turbulent throughout diastole, the injected indicator would be distributed uniformly across the aorta at any given point down its length. However, if laminar flow de- Table 1 Measurements and Calculations Carried Out on Three Subjects (C. H., C. P., F. T.), Each at Txco Different Heart Ttates HR Heart Rate (min."1) CO Cardiac output (liters/min.) BFD Backflow distance per stroke (cm.) BF/A = BFD X HR (cm./min.) BF at slow HE "BF~at fast HE C.H. 79 4.5 22 1740 1.61 F.T. C.P. 120 5.0 9 1080 84 6.2 10 750 120 6.0 4 360 60 5.3 19.5 1170 1.75 Circulation 105 6.5 6.5 685 1.71 Research, Volume IX, March 1901 AORTIC INSUFFICIENCY 417 Table 2 Calculations from Patient C. H. Using Equation (7) to Show the Effect of the Parameter (a) on the Expected Average Backflow at Two Heart Rate* Measured HE (min.-1) T\i (sec.) b (mm. Hg sec. cm. 4 ) k (sec."1) Po (mm. Hg) Assume a (mm. Hg sec." cm.""") Calculate ~BF" (litcr/min.-1) HP" 79 120 0.49 0.265 1 0.9 122 1 0.9 113 0 0.02 0.1 0 0.02 0.1 3.80 1.19 3.85 1.19 3.13 1.47 3.2 3.23 2.13 Downloaded from http://circres.ahajournals.org/ by guest on July 31, 2017 velops as the velocity of backflow diminishes late in diastole, the distribution of dye in the aorta 2 ' 3 will resemble that shown in figure 6. Under these circumstances, the maximum distance any dye particle travels back up the aorta during a single diastole may no longer be multipled by aortic cross section to estimate volume. Such an effect, if present, would be more prominent with the longer diastole, and would result in an overestimate of backflow by this method at the slower heart rates. The existence of such a phenomenon might be detected by high-speed cineangiography. This seems the most likely explanation of the results here presented. Summary Measurements of the distance a labeled particle of blood travels back up the descending aorta during a single diastole have been car- Circulation Retearch. Volume IX, March 1901 ried out at two different heart rates in each of three patients with aortic insufficiency. From these measurements, the ratios of backflow per unit time at the slow heart rate to backflow at the faster heart rate were found to be 1.61, 1.71, and 1.75. From an analysis of the hemodynamic factors involved, it seems likely that backflow is overestimated at the slow heart rates by this technique due to the development of laminar flow late in diastole. References 1. WARNER, H. E., AND TORONTO, A. F . : Quantita- tion of backflow in patients with aortic insufficiency using an indicator technic. Circulation Besearch 6: 29, 1958. 2. MCDONALD, D. A.: Occurrence of turbulent flow in the rabbit aorta. J. Physiol. 118: 340, 1952. 3. Rossi, H. H., POWERS, S. H., AND DWORK, B.: Measurement of flow in straight tubes by means of dilution technic. Am. J. Physiol. 173: 103, 1953. Effect of Heart Rate on Aortic Insufficiency as Measured by a Dye-Dilution Technique HOMER R. WARNER and ALAN F. TORONTO Downloaded from http://circres.ahajournals.org/ by guest on July 31, 2017 Circ Res. 1961;9:413-417 doi: 10.1161/01.RES.9.2.413 Circulation Research is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1961 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7330. Online ISSN: 1524-4571 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circres.ahajournals.org/content/9/2/413 Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation Research can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. 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