- Email: [email protected]
Measurement of right ventricular volumes using 131I-MAA
Measurement 13’l-MAA
of right ventricular
volumes
using
Toshio Sekimoto” Robert F. Grover** Denver, Colo.
When the contractile properties of the myocardium remain constant, then the contractile tension developed during systole is proportional to the diastolic fiber length, within limits. This length-tension relationship, when applied to the intact mammalian heart, indicates that the stroke work of systole is a function of end-diastolic volume, provided that myocardial contractility remains unchanged. This is the classical FrankStarling mechanism which determines the performance of the normal heart as a pump.5s 21 Within the limits of this concept, ventricular performance can be determined from measurements of end-diastolic volume, the subsequent stroke volume, the residual or end-systolic volume, and the pressure generated during systole. Various indicator dilution techniques have been employed by a number of investigators to measure volumes of the left ventricle in diastole and systole. Jacob and colleaguesll and, more recently, Wilckin2* estimated left ventricular volumes in man by means of the dye-dilution technique . Holtg obtained ventricular volume
From ment
the Cardiovascular Pulmonary Research of Medicine, University of Colorado School
Supported by Grant HL 14985 from the National stitute, National Institutes of Health, United Service. Received
for publication
May
Laboratory, of Medicine,
Heart and Lung InStates Public Health
‘7, 1974.
Reprint requests: Dr. Robert F. Grover, Cardiovascular Research Laboratory, University of Colorado Medical Ninth Ave., Denver, Colo. 80220.
Pulmonary Center, 4200
*Present address: Dr. Toshio Sekimoto. Chief of Cardiovascular sion, Shizuoka Red Cross Hospital, 8-2 Ohtemachi, Shizuoka-shi, Japan. **Recipient of Research Career Development National Heart and Lung Institute, National United States Public Health Service.
212
DepartDenver.
E.
Divi420,
Award HL-28,237 from Institutes of Health,
measurements by employing the dye-dilution method using T-1824 in combination with the electrical conductivity method with 4 per cent sodium chloride solution as the indicators. Rapaport, Wiegand, and Bristow17 applied the thermodilution technique injecting either room temperature saline or cooled autologous blood into the left ventricle of the dog to estimate the residual volume. Folse and Braunwald4 employed a precordial radioactivity counting system with the intraventricular injection of 1311-labeledDiodrast. Few studies of right ventricular volumes have been reported. Although the same methods as used for the left ventricle were applied for the right ventricle, i.e., dye-dilution,l, 6 electrical radioisotope dilution,2, 3, l3 and conductivity,1° thermodilution,12, 14.15*18 they have not been completely satisfactory because of technical difficulties resulting from the anatomic relationships of the right ventricle and the pulmonary artery. In radiocardiography with RIHSA,3 for instance, the down-slope of the time-activity curve from the right ventricle was prematurely interrupted at the time when the radioisotope appeared in the left side of the heart. Consequently, it was difficult to calculate an accurate value for the right ventricular volume. The thermodilution method with chilled saline possibly involved a technical error due to the heat transfer between the ventricular wall and the chamber blood.lg The purpose of this report is to describe a newly devised precordial counting method which could overcome the abovementioned difficulties in the measuring of right ventricular volumes during systole and diastole.
February,
1975, Vol. 89, No. 2, pp. 212-220
1. Radioisotope dilution curves following injection of 1331-MAA into the right ventricle. One 5clntiilatn3n ter positioned over the right ventricle (RV COUNT) detects the initial rise followed by an ~~~o~~e~~~a~ decline to a plateau. A second counter positioned over one lung (LUNG COUNT1 detects the 13”E-MAA as it is carried into the hmg and is trapped in the pulmonary capillaries, producing the plateau in both curves. This radioactivity from the lung, as recorded by the lung count, distorts the exponential down slope of the cilrve, as indicated in Fig. 2. ECG is the electrocardiogram.
In the initial series icular volumes were of the 14 dogs to establish the al variation among individuals. Duplicate erm~~atio~a were obtained in six of these dogs to estabhsh the reproducibility of the method. We also wished to know whether right ventricular function (as indicated by volumes) in a given dog vely constant over a period of sevth this objective, nine of the oriere restudied after an interval of one month. Healthy mongrel dogs, 18.9 + 1.9 6.D.) kilograms in weight, were anesthetized by the intravenous administration of 10 per cent chloralose in polyethylene glycol-200 in a dosage of 65 to 100 mg. per kilogram of body weight and were kept in a supine position for the duration of the experiment. Additional chloralose was administered as required. Ventilation was maintained by a volume-limited respirator (Harvard, Model 607). An electrocardiogram was obtained from limb leads. A polyethylene cannula was introduced into the femoral artery percutaneously according to the Seldinger technique to record the systemic blood pressure and to take blood
samples. A catheter with muleip:e h:?es at the tip ipolyethylene or NIH 6F (4r 33 was ~~tro~~~~d into the right heart via the expose for the purpose of injecting dye or dicator and determination of b!ood pressure in the right cardiac chambers or the ~~~~~0~~~~~ artery. Blood pressure was recor gauge pressure transclucers Cardiac output was measure tion method. Indocyanine green, 2.5 mg., was infected rapidly into the ~~lrno~~ar~ artery through the catheter. The c~n~entrat~~~ of dye iu the arterial blood withdrawn by a pump Model 600-910) at a speed of 19.4 nail. p via the arterial cannula was measured continu ously with a cuvette densit 25OAJ. The blood mination was imm animal. PO,, Pco,, and pH samples obtained anaerobic by appropriate electrodes C. C. and corrected to the rectal t~rn.~e~a~~~~ of the dog. The time-activity curve of ~~~~o~~t~ve i labeled rnac~~-aggregated a~~~~~~~ {I31 Iinjected into the right ntricle was3 recor rle the following manner.
Sekimoto
and
Grover
tion detector was positioned almost perpendicularly above the sternum at a distance of 2.5 cm. from the skin so that the aperture of the collimator pointed to the center of the right ventricular area determined by an x-ray film taken previously. A second detector was positioned over the lung field against a side wall of the chest horizontally to record the build-up curve from the lung. Approximately 100 microcuries of 131IMAA in a volume of 0.3 to 0.5 ml. was injected into the right ventricle followed with 5 ml. of saline in less than 1.0 second through the multiholed catheter tip (which had been withdrawn into the right ventricle from the pulmonary artery immediately after the measurement of cardiac output). The simultaneous time-activity curves from the right ventricle and the lung field were recorded at a chart speed of 50 mm. per second (Fig. 1). All of the records were made on a multichannel photographic oscillograph (Electronics for Medicine). The detectors employed in this study were scintillation counters containing a thallium-activated sodium iodide crystal 1 inch by 1 inch fitted with a brass collimator slightly tapered, 3 cm. in diameter with an aperture depth of 7 cm. beyond the crystal (Picker). The photomultipliers of both scintillation detectors were led into the count rate-meter with the time constant set at 0.1 second and a scale selection of 1,000 counts per minute. The output of the rate-meter was directly proportional to the radioactivity detected and was led to the direct current (DC!) preamplifier of the recorder. Calculations. According to the indicator dilution principle, if a known amount of radioactive indicator is injected rapidly into the right ventricular cavity and the time-activity curve is recorded by means of a scintillation counter placed over the precordium, the disappearance course of the indicator from the ventricle will be an exponential function of time, indicating the amount of isotope remaining in the ventricular blood at the end of each cardiac cycle. However, the random disintegration of isotope and the time constant of the rate meter make it impossible to record this process in an exponential steplike fashion on the time-activity curve. The down-slope, therefore, is simply assumed to be an exponential curve and the following formula is applied to calculate the right ventricular residual ratio:
214
ESVLEDV
= e-A* k
where, ESV is the end-systolic volume; EDV is the end-diastolic volume; ESV/EDV is the ventricular residual ratio (Appendix A); X is the slope of the straight line obtained by replotting the down-slope of the time-activity curve of the radioisotope on a semilogarithmic graph (Appendix B); t is an arbitrarily selected time interval in seconds; and N is the number of the heart beats in the period of t-seconds. Therefore, k is equivalent to the average R-R interval in seconds on the electrocardiogram. The fractions of right ventricular volume were then calculated according to Holt,gand the stroke work according to Holland and Klein%as follows: EDV =
stv 1 - ESVEDV
ESV = EDV - StV SW = stv XPa
+
p.S;;‘V2
where, StV is forward stroke volume in milliliters; SW is stroke work for the right ventricle in grams-centimeters; P,-, is mean pulmonary arterial pressure in centimeters of water; p is density of blood; V is velocity of ejection in centimeters per second; and G is the gravitational constant. It was observed that the majority of the timeactivity curves, when replotted semilogarithmically, deviated upward from a simple exponential in the latter part of the curve (Fig. 2) owing to the radioactivity which accumulated in that portion of the lung which intervened between the counter and the heart. In order to obtain the true exponential curve from the heart exclusively, it was necessary to subtract the lung build-up curve from the ventricular time-activity curve graphically, Once the 131I-MAA has been trapped in the pulmonary capillary bed, the radioactivity recorded by both the precordial and the lung detectors reaches a stable plateau. It is assumed that the MAA is distributed uniformly throughout the lung, i.e., that the radioactivity per unit of lung tissue is uniform. However, the total absolute radioactivity recorded by each detector will be dependent upon the volume of lung tissue seen by that detector. By intent, the precordial
February,
1975, Vol. 89, No. 2
1
2 3 4 5 5 7 a 3 LO 11 12 13 14 Mf?ElJl -L-l SD. One month
41.0 44.6
2.486
15.9
39.9
1.907
18.2 18.2 18.2 17.3 20.0 19.0 16.0 22.7 20.0 18.2 20.5 18.9
36.2 43.6 34.7 40.2 36.5 43.0 41.5 39.1 39.7 44.8 41.4 40.4
1.816 1.980 1.648 2.393 1.617 2.065 1.358 2.095 3.328 1.315 2.320
il.9
+3.1
19.5 16.8 LB.2 18.6 18.6 17.3
35.1 41.8 38.4 37.0 33.1 44.4 35.9
8 9
19.5 17.7
40.8 33.1
SD.
188 178 187 76
13.3 7.5 10.2 23.9
109
77 88 73 94 120 86 120 58 90
1.976 kO.548
110 -t44
2.437 1.700
190
116
1.579
113
14.0
2.172 1.938 2.165 1.792
72 74 102 96
30.2 26.2 21.2 18.7
2.010 1.283
69 51
29.1 25.2
1.329
9.2 7.0 6.8 13.6
22.5 14.5 17.0 37.5
16.0 12.0 21.0 13.0
307.9 132.4 305.5 455.3
18.2
15.0
33.2
15.0
395.9
21.4 27.2 22.2 22.0 11.3 24.4 27.7 22.7 25.8
11.4 18.3 12.8 16.6
32.8 45.5 35.0 38.6
13.0 20.0
407.7 U6.6 602.8
8.0
15.7 18.2 18.4 18.2
19.8 k6.6
19.0
29.Wl.Q 3O.QlO.G 41.011.0 32.011.0 36.012.0 3O.WZ.Q 30.012.0 31.012.0 27.011.5 14.OlO.5 23.Ol1.5 29.011.5 23.012.0 33.012.0 29.111.4
359.7
19.3
11.0 11.0
40.1 45.9
11.0 11.0
399.0
41.1 44.0
13.0 17.0
13.5 Ik4.4
33.4 k10.8
14.5 23.5
12.8
6.9
19.7
10.6 8.7 17.7 13.0
25.3 22.7 47.9 39.2
17.0 11.0 i4.0
313.0
14.7
17.0 15.0
738.4 569.9
16.9
38.1
15.0
461.1
10.4
29.1
16.0
433.0
34.0105 28.511.0 31.0/1.0 37.w3.0 32.Qil.5 29.0125 36.QD.O
20.1 12.4
49.2 37.6
16.0 10.0
673.7 376.8
35.011.5 21.0/2.0
184.8 453.0 432.5 630.9 417.4 k170.0
F6.4-+0.7
156 140 148 138 154 172
60.0 66.0 11.8 81.5 83.0 83.5
160
74.4
146 150 120 139 160 120 140 146
75.5 75.8 73.0 82.2 99.5 67.1 78.0
32.8 33.Q 36.5 27.11 22.2 26.9 33.2 34.3 30.7 24.8 34.7 33.5 33.7 33.0 31.6
215
i9.4
c4.9
160 148 146 154 148 162 158
81.8 66.0 88.9 88.0 81.7 76.5 77.0
27,5 23.0 22.0 19.3 27.5 35.6 31.5
7.378 7.395 1.400 7.553 7.410 7.306 7.365
44.5 47.Q 49.0 46.5 43.0 45.0
176 142
60.0 75.5
44..6 20.9
7.326 7.406
44.0 37.0
7.398
44.3
90.1
7.332 7.292 7.322 7.415 7.455 7.428 7.367 7.349 7.358 7.431 7.395 7.359 7.332 7.331 7.369 ~0.048
45.0 50.0 51.7 44.8 41.0 40.2 38.0 36.5 39.0 38.7 33.1 37.0 38.7 38.0 40.8 r5.2
later:
1 2 3 4 5 6 7
Mean
r?
20.4 20.4
19.1
18.4
37.1
1.897
21.0
t3.9
i-O.350
98 *41
240.4 284.9
21.3
13.0
34.3
14.6
454.6
+6.7
k4.4
+10.7
+2.5
*.l74.3
ESV/EDV = residual ratio, CO = cardiac output, HR = heart rate, PEA = mean pulmonary arterial pressure, SW = stroke work, PRVs/d t&al pnssun, Pa02 = arterial oxygen tension, Pwoz = arterial carbon
31.5!1.6 t4.9-+0.8
155
77.3
28.9
rtl0
t9.5
17.7
StV = stroke volume, ES’ = end-systolic voIume, EDV = right ventricular end-systolic and end-diastolic pmesuw, dioxide tensionl pHa = arterial pIf.
detector w~dl see a smaller amount of lung tissue. To adjust for these differences in the absolute levels of rad~oactiv~~~ in the final plateaus, the two plateaus are equated to 100 per cent. It is then possible to “‘correct” the precordial washout curve by subtracting from it a per cent of its final plateau equal to the simultaneously recorded per cent sf the final plateau in the lung. When this is done, and the “corrected” washout curve is plotted semi~ogar~tbmically, the resulting down slope becomes hear (Fig. 2). It is the slope, A , of this corrected curve which is then used to calculate the residual ratio.
A typical radioisotope dilution curve detected by the precordial scintillation counter following
-t&072 = end-draslniic PFA = mean
45.Q
1-3.7 volume, %emoml ar-
the instantaneous injection of l~~I-.M.AA !.nto the right ventricle is illustrated irb Fig. 1, The exponential gradient, h, determ~~od rrom the corrected semilogarithmic plot of this curve wa.s 1..278, which gives a resi ‘VI of 0.402, i.e., the residual, lume calculated by using X was per cent of the end-diastolic volume. Since the stroke volume calculated from the cardiac output measured simultaneously by the dye d~~~~~~~~~ ~~ethod was g, the calculated The data for each animal obt method are presented and ~~l~~~~~~~~d in ‘F&k Z. The residu ratio of the right ventricle was 40.4 + 3.1 @. j per cent and the stroke volume was 19.8 4 6.6 ml. Calculated ESV was then
Sekimoto
and Grover
II. Reproducibility ratio determinations Table
residual
Dog
First (%)
Second (%I
Difference
8
40.8 33.1 39.7 55.1 42.2 48.5
40.3 33.8 38.4 55.1 42.2 49.2
-0.5 0.7 1.3 0 0 0.7
No. 9 12 13 14 15
6
of duplicate
Mean SD. 0:5
1lo
13
= -0.07 t 0.76
2:o
SECONDS
Fig. 2. When the down slope of the RV COUNT curve from Fig. 1 is replotted semilogarithmically (triangles), the resulting “uncorrected” curve is not linear due to distortion by radioactivity from the lung. This distortion is removed by subtracting the lung count (see text). The resulting “corrected” curve (closed circles) is linear and its slope is then used to calculate the residual ratio.
stv ml
EDV
mI
Fig. 3. The dependence of stroke volume (StV) on enddiastolic volume (EDV) in keeping with the Frank-Starling mechanism. One data point from each of 14 individual dogs.
13.5 t 4.4 ml., and the corresponding EDV was 33.4 + 10.8 ml. Heart rate was 110 +- 44 beats per minute. Other parameters, i.e., pulmonary and systemic arterial pressures, cardiac output, hematocrit, and arterial blood-gases were as expected for dogs under chloralose anesthesia. Since these studies were performed in Denver at 1,600 meters of altitude where P, is 630 mm. Hg and P10s is 120 mm. Hg, the Pao, of 78 mm. Hg is also normal. Reproducibility. Duplicate isotope dilution curves were obtained in rapid succession in six
216
additional experiments while the heart rate remained unchanged either with or without atria1 pacing. The results (Table II) indicate that the reproducibility of the determination of the residual ratio is excellent. Variation in volumes among individuals. Under conditions of chloralose anesthesia with normal blood oxygenation and normal blood pH, the range in EDV was 17.0 to 49.2 ml. Right ventricular EDV is highly correlated with right ventricular end-diastolic (filling) pressure (r = 0.771, suggesting that variations in filling pressure among individuals account for much of the variation in EDV within the group. The duration of diastole will also influence EDV, as indicated by the negative correlation between heart rate and EDV (r = -0.77). Hence, individual differences in heart rate also contribute to the group variation in EDV. Since all dogs were studied under similar conditions, then to the extent that their myocardial contractile state was also similar, the FrankStarling mechanism should express the relationship between EDV and stroke volume. This was remarkably true for these group data as seen in Fig. 3. Mean pulmonary arterial pressure (PP,> was normal in all animals and, therefore, stroke volume was the major determinant of stroke work. Consequently, right ventricular stroke work was also highly correlated with EDV (r = 0.791 for this group of dogs. Even though stroke volume increased with increasing EDV, there was also an increase in residual ESV (Fig. 4). Consequently, the residual ratio tended to remain constant at 40.4 +- 3.1, as indicated by the minimal variation in the slope (ESV/EDV) of the data in Fig. 4. In other words,
February,
1975, Vol. 89, No. 2
the right ventricle ejects approximately 60 per cent of its EDV over the entire range of EDV observed in this group of dogs. ht ve~trjcuiar function. In nine dogs the initial study was followed by a second study one month later. Even if ventricular function remained constant, absolute volumes would be duplicated only if the ventricle happened to be operating at the same point on its normal function curve. Such a coincidence was improbable, and so it is more meaningful to examine the relationship between StV and EDV when comparing zhe two studies on each dog. Fig. 5 illustrates that the ventricular function curve which describes the original population of 14 dogs also describes ihe behavior of each individual dog when observed at two different times. In other words, when a given dog is studied under similar experimental conditions, his right ventricular function appears to remain relatively constant over an extended period of time. In general then, the variations in EDV observed in these dogs result from variations in the factors which normally determine EDV, and the Frank-Starling mechanism then accounts for the resulting variations in stroke volume, ESV, and stroke work.
ml
EDV
mi
Fig. 4. Since the r&t ventrlcie normaily ejects a ::onstant fraction of its end-diastolic volume CEDV), thert ~.ha ia.rger the EDV, the greater the volume of blood remaimng at the end of systole (ESV). The data from 14 individual dogs indicate this constancy of the residual ratio (ESV/E.DV) at ,40.4 F 3.1 per cent.
stv ?ni
3 D
ith data obtained
by other
Heart Jourplal
VALUE LATER
meth-
s. For the purpose of estimating the residual blood volume of the right ventricle, the dye dilution method was employed first by Bing, Heimcker, and Falholtl and, more recently, by Freis, vara, and G~~more.6~re~s,Rivara, and Gilmore reported the residual ratio to be 46.5 +- 5.4 per cent in man injecting indocyanine green into the right ventricle while sampling from the pulmonary artery. ‘This method, however, had an inherent potential error due to incomplete mixing of the dye with the ventricular blood and distortion of the time-concentration curve owing to the laminar flow in the sampling cathetersg, l6 Moreover, the necessity of introducing two catheters hmited the clinical application. Donato and co-workerq2* 3ll3 employing the radioisotope dilution method, reported the right ventricular residual ratio to be 57.5 +- 3.8 per cent in man. As apaport and co-workerPindieated, however, it appeared that sometimes the injection of RIHSA was not made into the right ventricle but into the right atrium. Furthermore,
American
“JiTlA: ’ I\?ONTH
6 ig. 5. Xine of the 14 dogs studied icitiaii:i were restudied one month later. The dependence of stoke voiume StV) on end-diastolic volume (EDV) observed iaitiai!y in Fig. 3 (open circles), was again demonstrated in ihe aecnnd study (closed circles). These data indicate that right venrricular function remains relatively constant over a period oi one month.
nential down slope of the riilution Curve uired for precise ~~~~~~~t~o~of the residual ratio tended to be in~e~~~~~,e~with early overlapping of the radioisotope act ing from the left side of the heart a apaport and as atio of 53.4 ic I.0 tne thermo~ilution technique in man. method, t, Sherman, and Gorin~‘~ indicate the pass of a technical error which might have resulted from heat transfer between the ventricular wall and the chamber blood: together
Sekimoto
and Grover
with a long sensor time constant. In human studies by Sekimoto (unpublished observations) employing 1311-MAA and precordial counting, the residual ratio of the right ventricle was 56.2 -t 6.5 per cent in five normal individuals. With regard to experiments on dogs, Holt and AllensworthlO applied the electrical conductivity method with concentrated salt solution as an indicator injected into the right ventricle to obtain the time-conductivity record of the blood in the pulmonary artery using a double-lumen electrical conductivity catheter. They determined the residual ratio to be 57.0 t 14.6 per cent in seven dogs. The major disadvantage of this method, as Goodwin and Sapirstein7 indicated, was that the electrical resistance of the blood was not predictably related to the indicator concentration. This made it neclessary to use an empirical calibration in vitro; it has never been ascertained that the in vitro calibration described the in vivo situation. In the present study, the average residual ratio of the right ventricle in 14 dogs was 40.4 t 3.1 per cent, which is smaller than that observed by Holt and Allensworth.l” This difference was attributed primarily to the myocardial depressant effect of the barbiturate anesthetic17, 2oused by Holt and Allensworth.l” Secondarily, the empirical calibration in vitro in the conductivity method might have raised the residual ratio erroneously.7 The method presented in the present study offers the following advantages. First, the dilution curve of 1311-MAA from the right ventricle is not obscured by the early appearance of the isotope in the left heart on the radiocardiogram because almost all of the particulates of MAA injected into the right ventricle are trapped in the pulmonary capillaries and do not reach to the left heart.22,23 Second, the difficulties resulting from inadequate mixing of indicator in the right ventricle were minimized by this technique because the total quantity of isotope in the right ventricle is evaluated as a whole by means of the scintillation counter placed on the precordium so as to cover the entire ventricular cavity. Third, the procedure is technically quite simple, making it easily applicable to both clinical and experimental investigations. When applied clinically, a more sensitive scintillation detector with a larger crystal (2 inch by 2 inch) should be employed,
218
thereby permitting the injection of a smaller dose of radioisotope. 133Xe030 kev.) or s5Kr (510 kev.) could be used as the indicator to obtain the right ventricular dilution curve since there would be no interference from radioactivity appearing early in the left heart. However, measurement with either of these isotope indicators would not necessarily be superior, for just as with 1311-MAA, the radioactivity transferred to the alveoli would disturb the true exponential downslope of the right ventricular dilution curve. Summary A method has been presented for determining the right ventricular residual ratio, that is, the ratio of the end-systolic volume to the enddiastolic volume during each cardiac cycle. 1311MAA was injected as a bolus into the right ventricle, and the ratio of isotope remaining in the chamber during the succeeding cardiac cycles was determined with a collimated scintillation counter placed over the right ventricle. Since the counter detected the radioactivity from the entire right ventricular cavity, potential errors from incomplete mixing were minimized. The washout curve from the ventricle was distorted somewhat by the accumulation of isotope in intervening lung tissue. This distortion was eliminated by subtracting the build-up curve of radioactivity in the lung recorded simultaneously with a second scintillation counter positioned over the lateral chest wall. In 14 dogs anesthetized with chloralose, the right ventricular residual ratio was relatively constant at 40.4 + 3.1 per cent. Duplicate measurements differed by lessthan 3 per cent indicating the good reproducibility of the method. Right ventricular stroke volume was determined from cardiac output (dye dilution1 and heart rate. With this and the simultaneously determined residual ratio (1311-MAA), enddiastolic volume could be calculated. Stroke volume and stroke work were highly correlated with end-diastolic volume, in keeping with the Frank-Starling mechanism. The authors express their gratitude to Gail Jamieson, Rosann Glas, Mary O’Sullivan, and Richard Trow for their technical assistance; to Diann Smith and Eva Toyos for blood-gas analysis; and Eleanor Register for skillful preparation of the manuscript.
February,
1975, Vol. 89, No. 2
1.
2.
3.
4.
5. 6.
7.
8.
9.
10.
11.
12.
Bing, R. J.: Meimbecker, R., and Falholt, W.: An estimation of the residual volume of blood in the right ventricle of normal and diseased hluman hearts in viva, AM. HEART J, 42:483,1951. Donato, L., Guintini, C., Lewis, M. L., Durand, J., Rochester, D. F., Harvey, R. M., and Command, A.: Quantitative radiocardiography. I. Theoretical considerations, Circulation 26~174, 1962. Donato, L., Rochester, D. F., Lewis, M. L., Durand, J., Parker, J. O., and Harvey, R. M.: Quantitative radiocardiography. II. Technique and analysis of curves, Circulation 26~183, 1962. False, R., and Braunwald, E.: Determination of fraction of left ventricular volume ejected per beat and of ventricular end-diastolic and residual volumes; experimental and clinical observations with a precordial dilution technic, Circulation 25:674, 1962. Frank, 0.: On the dynamics of cardiac muscle, AM. HEARTJ. 58:282,1959. Freis, E. D., Rivara, G. L.; and Gilmore, B. L.: Estimation of residual and end-diastolic volumes of the right ventricle of men without heart disease using the dyedilutionmethod,A~. HEARTJ. 60:898,1960. Goodwin, R. S., and Sapirstein, L. A.: Measurement of the cardiac output in dogs by a conductivity method after single intravenous injections of autogenous plasma, Circ. Res. 5~531, 1957. Kiolland, W., and Klein, R. L.: The Chemistry of Heart Failure, Springfield, Ill., 1960, Charles C Thomas, Publisher, p. 16. Halt, ,J. P.: Estimation of the residual volume of the ventricle of the dog’s heart by two indicator dilution techniques, Circ. Res. 4:187, 1956. Holt, J. I’., and Allensworth, J.: Estimation of the residnal volume bf the right ventricle of the dog’s heart, Cire. Res. 6:323,1957. Von Jacob, R., Bauereisen, E., Hauck, G., and Peiper, U.: Die Bestimmung des Ventrikel-innenvolumens mittels Farbstoffverdunnungskurven, Arch. Kreislaufforsch. 39:182, 1962. Kreuzer, H., Bostroem, B., and Loogen, F.: Das enddiastolisehe und end-systolische Volumen des rechten Ventrikels beim Menschen in Ruhe. 2. Kreislaufforsch. 53590,
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Rapaport, E., Wong, M., Ferguson, and Wiegand, B.: Right ventricular with and without heart failure,
R. E., Bernstein, P., volumes in patients Circulation 31:531,
1965. 19.
Rolett,
E., Sherman,
H., and Gorlin,
R.: Measurement
of
20.
21.
22.
23.
‘eit ventricular vo:ume by therrao~;r:iiL10.*~ An agprarsa: of technical errors, J. Appl. Physiol. 1 Shaffer, A. 8.: Estimation of ventricular volumes by a constant infusion indicator dilution technique? Circ. Res. 15168, 1965. Starling, E. H.: The Linacre Lecture on ihe Law of the lieart, London, 1918, Longman’s, Greeri & Co., Publisher, p. 21. Tow, Il. E., Wagner, II. N., Lo~e~~~~~j~~~), V., Smith: E. M., and Migita, T: Validity of measuring regional pdmonary arterial blood flow with macroaggregates of human serum albumin, Am. J. Roentgenol. Rad. Ther. Nuci. Med. 98:664, 1966. Wagner, II. N., Sabiston, D. C.. McAfee, VT. G., Tow, D., and Stern, II. S.: Diagnosis of massi.ve pulmonary embolism in man by radioisotope scanning. X. Engl. J. Med. 271:377,1964.
24.
Wilcken. 15. E. L.: The measurement of the end-diastolic and end-systolic, or residual, vol.umes of the left ventricle in man using a dye-dilution method, Clin. Sci. 2%Z131,1965.
lculation of tile ventricular DV from the iso where
ESV
= e
?k%dua:
mtm
Sekimoto md Grover
Em=
I,
- IL1
- I,,,“‘=
I,-,
From the electrocardiogram, erage R-R interval.
I,-,
Appendix
The quantity of indicator decreases exponentially,
/ 4 / Ia ~_._ \,: ‘/ / ; ‘x In ,---.-1..-..>,
I = I, e-ht then
in the ventricle
I, = I,eehta I, = I,e-An =
Log1
/ 11
1, e-*tn
ta _ e-A(tn-ta)
B
The exponential gradient, A, is calculated using regular logarithms as follows: from a general equation of I=
I = I,.dt
t/N equals the av-
= = = = =
%I
I, + e-At log I, * e-At log I, + log log I, - At. log I, - At. -0.4343 At
10” log IO eWxt log e. 0.4343 + log I,
~Log 1 -t
I,e-Ata
-0.4343h
1. Ij -I
I II. 0
t
+ Log IO L
let N be the number of cardiac which occur in t seconds, i.e. t, - t,
c-1 ESV EDV
ESV
N = e-it -
e-“t
cycles
L
n- a therefore,
-A
=
logIlog10 0.4343 t
N
EDV
220
February,
1975, Vol. 89, No. 2
of right ventricular
volumes
using
Toshio Sekimoto” Robert F. Grover** Denver, Colo.
When the contractile properties of the myocardium remain constant, then the contractile tension developed during systole is proportional to the diastolic fiber length, within limits. This length-tension relationship, when applied to the intact mammalian heart, indicates that the stroke work of systole is a function of end-diastolic volume, provided that myocardial contractility remains unchanged. This is the classical FrankStarling mechanism which determines the performance of the normal heart as a pump.5s 21 Within the limits of this concept, ventricular performance can be determined from measurements of end-diastolic volume, the subsequent stroke volume, the residual or end-systolic volume, and the pressure generated during systole. Various indicator dilution techniques have been employed by a number of investigators to measure volumes of the left ventricle in diastole and systole. Jacob and colleaguesll and, more recently, Wilckin2* estimated left ventricular volumes in man by means of the dye-dilution technique . Holtg obtained ventricular volume
From ment
the Cardiovascular Pulmonary Research of Medicine, University of Colorado School
Supported by Grant HL 14985 from the National stitute, National Institutes of Health, United Service. Received
for publication
May
Laboratory, of Medicine,
Heart and Lung InStates Public Health
‘7, 1974.
Reprint requests: Dr. Robert F. Grover, Cardiovascular Research Laboratory, University of Colorado Medical Ninth Ave., Denver, Colo. 80220.
Pulmonary Center, 4200
*Present address: Dr. Toshio Sekimoto. Chief of Cardiovascular sion, Shizuoka Red Cross Hospital, 8-2 Ohtemachi, Shizuoka-shi, Japan. **Recipient of Research Career Development National Heart and Lung Institute, National United States Public Health Service.
212
DepartDenver.
E.
Divi420,
Award HL-28,237 from Institutes of Health,
measurements by employing the dye-dilution method using T-1824 in combination with the electrical conductivity method with 4 per cent sodium chloride solution as the indicators. Rapaport, Wiegand, and Bristow17 applied the thermodilution technique injecting either room temperature saline or cooled autologous blood into the left ventricle of the dog to estimate the residual volume. Folse and Braunwald4 employed a precordial radioactivity counting system with the intraventricular injection of 1311-labeledDiodrast. Few studies of right ventricular volumes have been reported. Although the same methods as used for the left ventricle were applied for the right ventricle, i.e., dye-dilution,l, 6 electrical radioisotope dilution,2, 3, l3 and conductivity,1° thermodilution,12, 14.15*18 they have not been completely satisfactory because of technical difficulties resulting from the anatomic relationships of the right ventricle and the pulmonary artery. In radiocardiography with RIHSA,3 for instance, the down-slope of the time-activity curve from the right ventricle was prematurely interrupted at the time when the radioisotope appeared in the left side of the heart. Consequently, it was difficult to calculate an accurate value for the right ventricular volume. The thermodilution method with chilled saline possibly involved a technical error due to the heat transfer between the ventricular wall and the chamber blood.lg The purpose of this report is to describe a newly devised precordial counting method which could overcome the abovementioned difficulties in the measuring of right ventricular volumes during systole and diastole.
February,
1975, Vol. 89, No. 2, pp. 212-220
1. Radioisotope dilution curves following injection of 1331-MAA into the right ventricle. One 5clntiilatn3n ter positioned over the right ventricle (RV COUNT) detects the initial rise followed by an ~~~o~~e~~~a~ decline to a plateau. A second counter positioned over one lung (LUNG COUNT1 detects the 13”E-MAA as it is carried into the hmg and is trapped in the pulmonary capillaries, producing the plateau in both curves. This radioactivity from the lung, as recorded by the lung count, distorts the exponential down slope of the cilrve, as indicated in Fig. 2. ECG is the electrocardiogram.
In the initial series icular volumes were of the 14 dogs to establish the al variation among individuals. Duplicate erm~~atio~a were obtained in six of these dogs to estabhsh the reproducibility of the method. We also wished to know whether right ventricular function (as indicated by volumes) in a given dog vely constant over a period of sevth this objective, nine of the oriere restudied after an interval of one month. Healthy mongrel dogs, 18.9 + 1.9 6.D.) kilograms in weight, were anesthetized by the intravenous administration of 10 per cent chloralose in polyethylene glycol-200 in a dosage of 65 to 100 mg. per kilogram of body weight and were kept in a supine position for the duration of the experiment. Additional chloralose was administered as required. Ventilation was maintained by a volume-limited respirator (Harvard, Model 607). An electrocardiogram was obtained from limb leads. A polyethylene cannula was introduced into the femoral artery percutaneously according to the Seldinger technique to record the systemic blood pressure and to take blood
samples. A catheter with muleip:e h:?es at the tip ipolyethylene or NIH 6F (4r 33 was ~~tro~~~~d into the right heart via the expose for the purpose of injecting dye or dicator and determination of b!ood pressure in the right cardiac chambers or the ~~~~~0~~~~~ artery. Blood pressure was recor gauge pressure transclucers Cardiac output was measure tion method. Indocyanine green, 2.5 mg., was infected rapidly into the ~~lrno~~ar~ artery through the catheter. The c~n~entrat~~~ of dye iu the arterial blood withdrawn by a pump Model 600-910) at a speed of 19.4 nail. p via the arterial cannula was measured continu ously with a cuvette densit 25OAJ. The blood mination was imm animal. PO,, Pco,, and pH samples obtained anaerobic by appropriate electrodes C. C. and corrected to the rectal t~rn.~e~a~~~~ of the dog. The time-activity curve of ~~~~o~~t~ve i labeled rnac~~-aggregated a~~~~~~~ {I31 Iinjected into the right ntricle was3 recor rle the following manner.
Sekimoto
and
Grover
tion detector was positioned almost perpendicularly above the sternum at a distance of 2.5 cm. from the skin so that the aperture of the collimator pointed to the center of the right ventricular area determined by an x-ray film taken previously. A second detector was positioned over the lung field against a side wall of the chest horizontally to record the build-up curve from the lung. Approximately 100 microcuries of 131IMAA in a volume of 0.3 to 0.5 ml. was injected into the right ventricle followed with 5 ml. of saline in less than 1.0 second through the multiholed catheter tip (which had been withdrawn into the right ventricle from the pulmonary artery immediately after the measurement of cardiac output). The simultaneous time-activity curves from the right ventricle and the lung field were recorded at a chart speed of 50 mm. per second (Fig. 1). All of the records were made on a multichannel photographic oscillograph (Electronics for Medicine). The detectors employed in this study were scintillation counters containing a thallium-activated sodium iodide crystal 1 inch by 1 inch fitted with a brass collimator slightly tapered, 3 cm. in diameter with an aperture depth of 7 cm. beyond the crystal (Picker). The photomultipliers of both scintillation detectors were led into the count rate-meter with the time constant set at 0.1 second and a scale selection of 1,000 counts per minute. The output of the rate-meter was directly proportional to the radioactivity detected and was led to the direct current (DC!) preamplifier of the recorder. Calculations. According to the indicator dilution principle, if a known amount of radioactive indicator is injected rapidly into the right ventricular cavity and the time-activity curve is recorded by means of a scintillation counter placed over the precordium, the disappearance course of the indicator from the ventricle will be an exponential function of time, indicating the amount of isotope remaining in the ventricular blood at the end of each cardiac cycle. However, the random disintegration of isotope and the time constant of the rate meter make it impossible to record this process in an exponential steplike fashion on the time-activity curve. The down-slope, therefore, is simply assumed to be an exponential curve and the following formula is applied to calculate the right ventricular residual ratio:
214
ESVLEDV
= e-A* k
where, ESV is the end-systolic volume; EDV is the end-diastolic volume; ESV/EDV is the ventricular residual ratio (Appendix A); X is the slope of the straight line obtained by replotting the down-slope of the time-activity curve of the radioisotope on a semilogarithmic graph (Appendix B); t is an arbitrarily selected time interval in seconds; and N is the number of the heart beats in the period of t-seconds. Therefore, k is equivalent to the average R-R interval in seconds on the electrocardiogram. The fractions of right ventricular volume were then calculated according to Holt,gand the stroke work according to Holland and Klein%as follows: EDV =
stv 1 - ESVEDV
ESV = EDV - StV SW = stv XPa
+
p.S;;‘V2
where, StV is forward stroke volume in milliliters; SW is stroke work for the right ventricle in grams-centimeters; P,-, is mean pulmonary arterial pressure in centimeters of water; p is density of blood; V is velocity of ejection in centimeters per second; and G is the gravitational constant. It was observed that the majority of the timeactivity curves, when replotted semilogarithmically, deviated upward from a simple exponential in the latter part of the curve (Fig. 2) owing to the radioactivity which accumulated in that portion of the lung which intervened between the counter and the heart. In order to obtain the true exponential curve from the heart exclusively, it was necessary to subtract the lung build-up curve from the ventricular time-activity curve graphically, Once the 131I-MAA has been trapped in the pulmonary capillary bed, the radioactivity recorded by both the precordial and the lung detectors reaches a stable plateau. It is assumed that the MAA is distributed uniformly throughout the lung, i.e., that the radioactivity per unit of lung tissue is uniform. However, the total absolute radioactivity recorded by each detector will be dependent upon the volume of lung tissue seen by that detector. By intent, the precordial
February,
1975, Vol. 89, No. 2
1
2 3 4 5 5 7 a 3 LO 11 12 13 14 Mf?ElJl -L-l SD. One month
41.0 44.6
2.486
15.9
39.9
1.907
18.2 18.2 18.2 17.3 20.0 19.0 16.0 22.7 20.0 18.2 20.5 18.9
36.2 43.6 34.7 40.2 36.5 43.0 41.5 39.1 39.7 44.8 41.4 40.4
1.816 1.980 1.648 2.393 1.617 2.065 1.358 2.095 3.328 1.315 2.320
il.9
+3.1
19.5 16.8 LB.2 18.6 18.6 17.3
35.1 41.8 38.4 37.0 33.1 44.4 35.9
8 9
19.5 17.7
40.8 33.1
SD.
188 178 187 76
13.3 7.5 10.2 23.9
109
77 88 73 94 120 86 120 58 90
1.976 kO.548
110 -t44
2.437 1.700
190
116
1.579
113
14.0
2.172 1.938 2.165 1.792
72 74 102 96
30.2 26.2 21.2 18.7
2.010 1.283
69 51
29.1 25.2
1.329
9.2 7.0 6.8 13.6
22.5 14.5 17.0 37.5
16.0 12.0 21.0 13.0
307.9 132.4 305.5 455.3
18.2
15.0
33.2
15.0
395.9
21.4 27.2 22.2 22.0 11.3 24.4 27.7 22.7 25.8
11.4 18.3 12.8 16.6
32.8 45.5 35.0 38.6
13.0 20.0
407.7 U6.6 602.8
8.0
15.7 18.2 18.4 18.2
19.8 k6.6
19.0
29.Wl.Q 3O.QlO.G 41.011.0 32.011.0 36.012.0 3O.WZ.Q 30.012.0 31.012.0 27.011.5 14.OlO.5 23.Ol1.5 29.011.5 23.012.0 33.012.0 29.111.4
359.7
19.3
11.0 11.0
40.1 45.9
11.0 11.0
399.0
41.1 44.0
13.0 17.0
13.5 Ik4.4
33.4 k10.8
14.5 23.5
12.8
6.9
19.7
10.6 8.7 17.7 13.0
25.3 22.7 47.9 39.2
17.0 11.0 i4.0
313.0
14.7
17.0 15.0
738.4 569.9
16.9
38.1
15.0
461.1
10.4
29.1
16.0
433.0
34.0105 28.511.0 31.0/1.0 37.w3.0 32.Qil.5 29.0125 36.QD.O
20.1 12.4
49.2 37.6
16.0 10.0
673.7 376.8
35.011.5 21.0/2.0
184.8 453.0 432.5 630.9 417.4 k170.0
F6.4-+0.7
156 140 148 138 154 172
60.0 66.0 11.8 81.5 83.0 83.5
160
74.4
146 150 120 139 160 120 140 146
75.5 75.8 73.0 82.2 99.5 67.1 78.0
32.8 33.Q 36.5 27.11 22.2 26.9 33.2 34.3 30.7 24.8 34.7 33.5 33.7 33.0 31.6
215
i9.4
c4.9
160 148 146 154 148 162 158
81.8 66.0 88.9 88.0 81.7 76.5 77.0
27,5 23.0 22.0 19.3 27.5 35.6 31.5
7.378 7.395 1.400 7.553 7.410 7.306 7.365
44.5 47.Q 49.0 46.5 43.0 45.0
176 142
60.0 75.5
44..6 20.9
7.326 7.406
44.0 37.0
7.398
44.3
90.1
7.332 7.292 7.322 7.415 7.455 7.428 7.367 7.349 7.358 7.431 7.395 7.359 7.332 7.331 7.369 ~0.048
45.0 50.0 51.7 44.8 41.0 40.2 38.0 36.5 39.0 38.7 33.1 37.0 38.7 38.0 40.8 r5.2
later:
1 2 3 4 5 6 7
Mean
r?
20.4 20.4
19.1
18.4
37.1
1.897
21.0
t3.9
i-O.350
98 *41
240.4 284.9
21.3
13.0
34.3
14.6
454.6
+6.7
k4.4
+10.7
+2.5
*.l74.3
ESV/EDV = residual ratio, CO = cardiac output, HR = heart rate, PEA = mean pulmonary arterial pressure, SW = stroke work, PRVs/d t&al pnssun, Pa02 = arterial oxygen tension, Pwoz = arterial carbon
31.5!1.6 t4.9-+0.8
155
77.3
28.9
rtl0
t9.5
17.7
StV = stroke volume, ES’ = end-systolic voIume, EDV = right ventricular end-systolic and end-diastolic pmesuw, dioxide tensionl pHa = arterial pIf.
detector w~dl see a smaller amount of lung tissue. To adjust for these differences in the absolute levels of rad~oactiv~~~ in the final plateaus, the two plateaus are equated to 100 per cent. It is then possible to “‘correct” the precordial washout curve by subtracting from it a per cent of its final plateau equal to the simultaneously recorded per cent sf the final plateau in the lung. When this is done, and the “corrected” washout curve is plotted semi~ogar~tbmically, the resulting down slope becomes hear (Fig. 2). It is the slope, A , of this corrected curve which is then used to calculate the residual ratio.
A typical radioisotope dilution curve detected by the precordial scintillation counter following
-t&072 = end-draslniic PFA = mean
45.Q
1-3.7 volume, %emoml ar-
the instantaneous injection of l~~I-.M.AA !.nto the right ventricle is illustrated irb Fig. 1, The exponential gradient, h, determ~~od rrom the corrected semilogarithmic plot of this curve wa.s 1..278, which gives a resi ‘VI of 0.402, i.e., the residual, lume calculated by using X was per cent of the end-diastolic volume. Since the stroke volume calculated from the cardiac output measured simultaneously by the dye d~~~~~~~~~ ~~ethod was g, the calculated The data for each animal obt method are presented and ~~l~~~~~~~~d in ‘F&k Z. The residu ratio of the right ventricle was 40.4 + 3.1 @. j per cent and the stroke volume was 19.8 4 6.6 ml. Calculated ESV was then
Sekimoto
and Grover
II. Reproducibility ratio determinations Table
residual
Dog
First (%)
Second (%I
Difference
8
40.8 33.1 39.7 55.1 42.2 48.5
40.3 33.8 38.4 55.1 42.2 49.2
-0.5 0.7 1.3 0 0 0.7
No. 9 12 13 14 15
6
of duplicate
Mean SD. 0:5
1lo
13
= -0.07 t 0.76
2:o
SECONDS
Fig. 2. When the down slope of the RV COUNT curve from Fig. 1 is replotted semilogarithmically (triangles), the resulting “uncorrected” curve is not linear due to distortion by radioactivity from the lung. This distortion is removed by subtracting the lung count (see text). The resulting “corrected” curve (closed circles) is linear and its slope is then used to calculate the residual ratio.
stv ml
EDV
mI
Fig. 3. The dependence of stroke volume (StV) on enddiastolic volume (EDV) in keeping with the Frank-Starling mechanism. One data point from each of 14 individual dogs.
13.5 t 4.4 ml., and the corresponding EDV was 33.4 + 10.8 ml. Heart rate was 110 +- 44 beats per minute. Other parameters, i.e., pulmonary and systemic arterial pressures, cardiac output, hematocrit, and arterial blood-gases were as expected for dogs under chloralose anesthesia. Since these studies were performed in Denver at 1,600 meters of altitude where P, is 630 mm. Hg and P10s is 120 mm. Hg, the Pao, of 78 mm. Hg is also normal. Reproducibility. Duplicate isotope dilution curves were obtained in rapid succession in six
216
additional experiments while the heart rate remained unchanged either with or without atria1 pacing. The results (Table II) indicate that the reproducibility of the determination of the residual ratio is excellent. Variation in volumes among individuals. Under conditions of chloralose anesthesia with normal blood oxygenation and normal blood pH, the range in EDV was 17.0 to 49.2 ml. Right ventricular EDV is highly correlated with right ventricular end-diastolic (filling) pressure (r = 0.771, suggesting that variations in filling pressure among individuals account for much of the variation in EDV within the group. The duration of diastole will also influence EDV, as indicated by the negative correlation between heart rate and EDV (r = -0.77). Hence, individual differences in heart rate also contribute to the group variation in EDV. Since all dogs were studied under similar conditions, then to the extent that their myocardial contractile state was also similar, the FrankStarling mechanism should express the relationship between EDV and stroke volume. This was remarkably true for these group data as seen in Fig. 3. Mean pulmonary arterial pressure (PP,> was normal in all animals and, therefore, stroke volume was the major determinant of stroke work. Consequently, right ventricular stroke work was also highly correlated with EDV (r = 0.791 for this group of dogs. Even though stroke volume increased with increasing EDV, there was also an increase in residual ESV (Fig. 4). Consequently, the residual ratio tended to remain constant at 40.4 +- 3.1, as indicated by the minimal variation in the slope (ESV/EDV) of the data in Fig. 4. In other words,
February,
1975, Vol. 89, No. 2
the right ventricle ejects approximately 60 per cent of its EDV over the entire range of EDV observed in this group of dogs. ht ve~trjcuiar function. In nine dogs the initial study was followed by a second study one month later. Even if ventricular function remained constant, absolute volumes would be duplicated only if the ventricle happened to be operating at the same point on its normal function curve. Such a coincidence was improbable, and so it is more meaningful to examine the relationship between StV and EDV when comparing zhe two studies on each dog. Fig. 5 illustrates that the ventricular function curve which describes the original population of 14 dogs also describes ihe behavior of each individual dog when observed at two different times. In other words, when a given dog is studied under similar experimental conditions, his right ventricular function appears to remain relatively constant over an extended period of time. In general then, the variations in EDV observed in these dogs result from variations in the factors which normally determine EDV, and the Frank-Starling mechanism then accounts for the resulting variations in stroke volume, ESV, and stroke work.
ml
EDV
mi
Fig. 4. Since the r&t ventrlcie normaily ejects a ::onstant fraction of its end-diastolic volume CEDV), thert ~.ha ia.rger the EDV, the greater the volume of blood remaimng at the end of systole (ESV). The data from 14 individual dogs indicate this constancy of the residual ratio (ESV/E.DV) at ,40.4 F 3.1 per cent.
stv ?ni
3 D
ith data obtained
by other
Heart Jourplal
VALUE LATER
meth-
s. For the purpose of estimating the residual blood volume of the right ventricle, the dye dilution method was employed first by Bing, Heimcker, and Falholtl and, more recently, by Freis, vara, and G~~more.6~re~s,Rivara, and Gilmore reported the residual ratio to be 46.5 +- 5.4 per cent in man injecting indocyanine green into the right ventricle while sampling from the pulmonary artery. ‘This method, however, had an inherent potential error due to incomplete mixing of the dye with the ventricular blood and distortion of the time-concentration curve owing to the laminar flow in the sampling cathetersg, l6 Moreover, the necessity of introducing two catheters hmited the clinical application. Donato and co-workerq2* 3ll3 employing the radioisotope dilution method, reported the right ventricular residual ratio to be 57.5 +- 3.8 per cent in man. As apaport and co-workerPindieated, however, it appeared that sometimes the injection of RIHSA was not made into the right ventricle but into the right atrium. Furthermore,
American
“JiTlA: ’ I\?ONTH
6 ig. 5. Xine of the 14 dogs studied icitiaii:i were restudied one month later. The dependence of stoke voiume StV) on end-diastolic volume (EDV) observed iaitiai!y in Fig. 3 (open circles), was again demonstrated in ihe aecnnd study (closed circles). These data indicate that right venrricular function remains relatively constant over a period oi one month.
nential down slope of the riilution Curve uired for precise ~~~~~~~t~o~of the residual ratio tended to be in~e~~~~~,e~with early overlapping of the radioisotope act ing from the left side of the heart a apaport and as atio of 53.4 ic I.0 tne thermo~ilution technique in man. method, t, Sherman, and Gorin~‘~ indicate the pass of a technical error which might have resulted from heat transfer between the ventricular wall and the chamber blood: together
Sekimoto
and Grover
with a long sensor time constant. In human studies by Sekimoto (unpublished observations) employing 1311-MAA and precordial counting, the residual ratio of the right ventricle was 56.2 -t 6.5 per cent in five normal individuals. With regard to experiments on dogs, Holt and AllensworthlO applied the electrical conductivity method with concentrated salt solution as an indicator injected into the right ventricle to obtain the time-conductivity record of the blood in the pulmonary artery using a double-lumen electrical conductivity catheter. They determined the residual ratio to be 57.0 t 14.6 per cent in seven dogs. The major disadvantage of this method, as Goodwin and Sapirstein7 indicated, was that the electrical resistance of the blood was not predictably related to the indicator concentration. This made it neclessary to use an empirical calibration in vitro; it has never been ascertained that the in vitro calibration described the in vivo situation. In the present study, the average residual ratio of the right ventricle in 14 dogs was 40.4 t 3.1 per cent, which is smaller than that observed by Holt and Allensworth.l” This difference was attributed primarily to the myocardial depressant effect of the barbiturate anesthetic17, 2oused by Holt and Allensworth.l” Secondarily, the empirical calibration in vitro in the conductivity method might have raised the residual ratio erroneously.7 The method presented in the present study offers the following advantages. First, the dilution curve of 1311-MAA from the right ventricle is not obscured by the early appearance of the isotope in the left heart on the radiocardiogram because almost all of the particulates of MAA injected into the right ventricle are trapped in the pulmonary capillaries and do not reach to the left heart.22,23 Second, the difficulties resulting from inadequate mixing of indicator in the right ventricle were minimized by this technique because the total quantity of isotope in the right ventricle is evaluated as a whole by means of the scintillation counter placed on the precordium so as to cover the entire ventricular cavity. Third, the procedure is technically quite simple, making it easily applicable to both clinical and experimental investigations. When applied clinically, a more sensitive scintillation detector with a larger crystal (2 inch by 2 inch) should be employed,
218
thereby permitting the injection of a smaller dose of radioisotope. 133Xe030 kev.) or s5Kr (510 kev.) could be used as the indicator to obtain the right ventricular dilution curve since there would be no interference from radioactivity appearing early in the left heart. However, measurement with either of these isotope indicators would not necessarily be superior, for just as with 1311-MAA, the radioactivity transferred to the alveoli would disturb the true exponential downslope of the right ventricular dilution curve. Summary A method has been presented for determining the right ventricular residual ratio, that is, the ratio of the end-systolic volume to the enddiastolic volume during each cardiac cycle. 1311MAA was injected as a bolus into the right ventricle, and the ratio of isotope remaining in the chamber during the succeeding cardiac cycles was determined with a collimated scintillation counter placed over the right ventricle. Since the counter detected the radioactivity from the entire right ventricular cavity, potential errors from incomplete mixing were minimized. The washout curve from the ventricle was distorted somewhat by the accumulation of isotope in intervening lung tissue. This distortion was eliminated by subtracting the build-up curve of radioactivity in the lung recorded simultaneously with a second scintillation counter positioned over the lateral chest wall. In 14 dogs anesthetized with chloralose, the right ventricular residual ratio was relatively constant at 40.4 + 3.1 per cent. Duplicate measurements differed by lessthan 3 per cent indicating the good reproducibility of the method. Right ventricular stroke volume was determined from cardiac output (dye dilution1 and heart rate. With this and the simultaneously determined residual ratio (1311-MAA), enddiastolic volume could be calculated. Stroke volume and stroke work were highly correlated with end-diastolic volume, in keeping with the Frank-Starling mechanism. The authors express their gratitude to Gail Jamieson, Rosann Glas, Mary O’Sullivan, and Richard Trow for their technical assistance; to Diann Smith and Eva Toyos for blood-gas analysis; and Eleanor Register for skillful preparation of the manuscript.
February,
1975, Vol. 89, No. 2
1.
2.
3.
4.
5. 6.
7.
8.
9.
10.
11.
12.
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lculation of tile ventricular DV from the iso where
ESV
= e
?k%dua:
mtm
Sekimoto md Grover
Em=
I,
- IL1
- I,,,“‘=
I,-,
From the electrocardiogram, erage R-R interval.
I,-,
Appendix
The quantity of indicator decreases exponentially,
/ 4 / Ia ~_._ \,: ‘/ / ; ‘x In ,---.-1..-..>,
I = I, e-ht then
in the ventricle
I, = I,eehta I, = I,e-An =
Log1
/ 11
1, e-*tn
ta _ e-A(tn-ta)
B
The exponential gradient, A, is calculated using regular logarithms as follows: from a general equation of I=
I = I,.dt
t/N equals the av-
= = = = =
%I
I, + e-At log I, * e-At log I, + log log I, - At. log I, - At. -0.4343 At
10” log IO eWxt log e. 0.4343 + log I,
~Log 1 -t
I,e-Ata
-0.4343h
1. Ij -I
I II. 0
t
+ Log IO L
let N be the number of cardiac which occur in t seconds, i.e. t, - t,
c-1 ESV EDV
ESV
N = e-it -
e-“t
cycles
L
n- a therefore,
-A
=
logIlog10 0.4343 t
N
EDV
220
February,
1975, Vol. 89, No. 2