Journal of Clinical InvestigationVol. 43, No. 6, 1964

Left Ventricular Volume Measurements in ManbyThermodilution *

J. DAVID BRISTOW, RODNEYL. CRISLIP, CYRUSFARREHI, WALDOE. HARRIS.RICHARDP. LEWIS, DONALDW. SUTHERLAND,ANDHERBERTE. GRISWOLD

(From the Division of Cardiology of the Department of Medicine, University of OregonMedical School, Portland, Oreg.)

A safe, rapid method for estimating left ven-tricular volume in man during the course of hemo-dynamic studies should prove helpful in the as-sessment of cardiac disease and useful in physio-logical research. It is the purpose of this reportto present left ventricular volume measurements inman that were obtained by an indicator dilutionmethod which employs cold as the indicator. Thiscirculatory indicator has been studied by severalworkers (1-4) and has been used for left ven-tricular volume determinations in animals previ-ously (5-10). The method employed was adaptedfrom those used by Rapaport and his co-workersfor left ventricular volume measurements in thedog (7) and right ventricular studies in man (11).

MethodsThirty-eight patients were studied during diagnostic

left heart catheterization. The left ventricle was cathe-terized by the percutaneous transseptal method, utilizinga Teflon catheter which has four side holes near itstip (12). Left atrial pressure was measured before andafter ventricular catheterization. A brachial artery wascannulated percutaneously with a 15-cm length of poly-ethylene tubing. A 6F Teflon catheter was introducedpercutaneously into the right femoral artery and ad-vanced until its tip was slightly above the aortic valve,as judged fluoroscopically. Left heart pressures weremeasured with a P-23G strain gage' and systemic ar-terial pressure with a P-23D gage.' These pressures andthe electrocardiogram were recorded with a direct-writ-ing four channel oscillograph.2

The measurement of left ventricular volume by indi-cator dilution requires determination of indicator con-centrations in the proximal aorta during a sequence ofbeats after left ventricular injection. It is importantthat this dilution curve not be deformed by the sampling

* Submitted for publication October 25, 1963; acceptedJanuary 15, 1964.

Supported by a program project grant (HE 06336-03)of the U. S. Public Health Service.

1 Statham Transducers, Inc., Hato Rey, Puerto Rico.2 Sanborn Co., Cambridge, Mass.

system and that it present an exponential series of de-creasing, steplike concentrations. In these studies coldwas used as the indicator and was delivered rapidly intothe left ventricle by injections of 5 ml of cooled saline.Rarely, 10- to 15-ml injections were given in patientswith extremely large ventricular volumes. A bead ther-mistor in the proximal aorta served as the sampling sys-tem. The thermistor catheter was of nylon (o. d., 0.97mm) with a closed end and had a rapidly responding ther-mistor bead mounted at its tip.3 This catheter was 1 cmlonger than the radiopaque aortic catheter and was in-serted into the latter when thermodilution curves wereto be recorded. This placed the thermistor into the bloodstream just above the aortic valve. Immediately afterrecording the thermodilution curves and cardiac outputby dye dilution, the aortic catheters were removed toavoid the possibility of thrombosis.

The thermistor was employed as one arm of a Wheat-stone bridge that was activated by a mercury battery.Approximately 0.1 v was presented to the thermistor itself.The resulting signal was amplified by a type 53/54 Dpreamplifier4 and displayed with a type RM 565 oscil-loscope.4 The electrocardiogram was displayed simul-taneously by a type 3 A 74 amplifying electronic switch.4Records were made by photographing the oscilloscopescreen with 35-mm film.

The thermistors were calibrated against known tem-perature in a water bath. The peak change in aorticblood temperature produced by the cold inj ections wasusually between 0.3° and 0.50 C. Since the changes inblood temperature were small, the thermistor could beused as a linearly responding system (7). The thermo-dilution curves were analyzed to obtain a dimensionlessratio, and therefore knowledge of the exact quantity ofcold injected was not required.

The cardiac output was determined by the dye dilu-tion method. Five mg of indocyanine green was rapidlyflushed into the left ventricle, and continuous samplingof blood from the brachial artery was achieved with a

cuvette densitometer5 and a constant rate withdrawalpump.6 The dilution curves were calibrated by passageof known concentrations of dye in arterial blood through

3 Victory Engineering Corp., Springfield, N. J.4Tektronix, Inc., Portland, Oreg.5 Colson Corp., Elyria, Ohio.6 Harvard Apparatus Co., Dover, Mass.

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BRISTOW, CRISLIP, FARREHI, HARRIS, LEWIS, SUTHERLAND,AND GRISWOLD

the densitometer. Stroke volume was calculated by di-viding the cardiac output by the heart rate which wasrecorded during the dilution curves.

Left ventricular volumes were calculated by formulasadapted from those published by Holt (13). Two basicmeasurements are required. The first is the forwardstroke volume, which was obtained from the dye dilutioncurves. The second is a series of indicator concentra-tion ratios in the downslope of an aortic dilution curveproduced by left ventricular injection of indicator. Thiswas provided by the thermodilution curve. The formulasare:

EDV = [1]1 T+,

T,

where EDV= end-diastolic ventricular volume, FSV=forward or effective stroke volume, and T. and T.+, =differences between base-line aortic blood temperatureand that resulting at beats n and n + 1 in the thermodi-lution curve. The average of 2 to 5 such ratios (T4/TS,T5/T4, T6/T5, and so forth) was used. The third beatafter injection was the first one employed in curves withrapid downslopes, and the fourth was the initial one usedin those with prolonged downslopes.

FSV/EDV(%) = 1 -T. X 100 [2]

andESV = EDV - FSV, [3]

where ESV= end-systolic ventricular volume, and thereis neither mitral nor aortic regurgitation. Expression 2represents the fraction of the EDV that is ejected asthe forward stroke volume. The formula for ESV canapply only when there is neither mitral nor aortic re-gurgitation. With aortic insufficiency, some of the indi-cator that left the ventricle with systole returns to it inthe next diastole, and the curve appears as though theregurgitant indicator did not leave the chamber. Thusthe calculated ESV also includes the regurgitant volume.However, the measurements of FSV/EDV and of EDVshould remain valid. In the presence of mitral regurgi-tation it is not possible theoretically to measure ventricu-lar EDV by this method. Indicator travels from theleft ventricle to the left atrium with systole, and it isuncertain that it all returns to the ventricle in the fol-lowing diastole. Thus volumes were not calculated inthe four patients with mitral insufficiency who had ther-modilution curves. Their results are stated as FSV/EDV, but the expression is interpreted empirically inthis case.

The patients had a variety of cardiac diseases as shownin Table I. They were categorized on the basis of theirclinical and catheterization findings. Five had apparentlynormal ventricular function at rest and are tabulated asthe miscellaneous group. They had normal left atrialmean and left ventricular end-diastolic pressures andwere free of any significant hemodynamic burden forthe left ventricle. Four of these were studied severalmonths after aortic commissurotomy or aortic valve re-

placement (two each), and three had small transvalvu-lar systolic pressure gradients. The fifth patient in thisgroup had an atrial septal defect. These five patientscannot be considered normal in a strict sense. The pa-tients with mitral stenosis had no clinical or hemodynamicevidence of mitral regurgitation. Those listed withaortic stenosis had peak systolic pressure gradients be-tween the left ventricle and the brachial artery of 24 to120 mmHg without evidence of severe aortic regurgi-tation. One patient in the aortic insufficiency grouphad a systolic transvalvular gradient of 30 mmHg buthad all other signs of gross regurgitation.

Patients came to the laboratory fasting and had re-ceived 100 mg of secobarbital or pentobarbital. From1 to 7 thermodilution curves were obtained in each pa-tient. The indocyanine green curve was recorded withor immediately before or after the thermal curves. Thecooled saline and dye inj ections were usually accom-plished within a 5-minute period.

Differences between various groups of patients wereanalyzed by the t test.

ResultsThe complete data are presented in Table I.

The volume results are corrected for body sizeand expressed as milliliters per square meter bodysurface area.

Deleterious effects from the injections of cooledsaline were not observed. Electrocardiographicchanges were not ~een, except for appearance ofa premature contraction in some patients at thetime of injection.

140 thermodilution curves were recorded inthe 38 patients, and a steplike washout of indica-tor from the left ventricle was consistently re-corded. Multiple curves were obtained in 36 pa-tients, and the reproducibility of the test is showngraphically in Figure 1. For further analysis ofreproducibility, the average ratio Tn+I/Tn for asingle curve was compared with the average valuefor all of the curves in that patient. The differ-ence was expressed as a percentage of this aver-age, without regard to sign. The mean differenceof Tn+1/Tn for a given curve from the averagefor that patient was 3.2 ± 3.1% (mean + 1 SD).Duplicate curves from a patient are presented inFigure 2.

The consistency of the exponential downslope ofthe thermodilution curves was analyzed in detail in84 curves from the first 23 patients studied. Theratio of each pair of downslope deflections (T4/T3,and so forth) was compared with the average ofsuch ratios for that curve. The difference was

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LEFT VENTRICULARVOLUMEMEASUREMENTSIN MANBY THERMODILUTION

TABLE I

Results in all patients studied

ESVand

- aortic Pressuresregur-

Heart Cardiac Stroke gitant FSV/ MeanPatient Age rate index index EDV vol EDV LA LV-t BA

L/min/M2 ml,, m2 nl/m2 mI/M2 % mmHgMiscellaneous group

1 45 76 2.28 30 100 70 302 18 72 3.00 41 124 83 333 12 102 4.58 45 83 38 544 32 64 2.96 46 100 54 465 33 103 2.44 24 89 65 27

Mean 28 83 -3.05 37

6 136/7 122/747 112/7- 104/686 160/10 164/602 140/5 122/725 100/4 102/72

99 62 38

Pure or predominant aortic stenosis6 45 78 2.64 34 117 83 297 12 78 2.71 35 67 32 528 40 93 2.76 30 130 100 239 61 78 2.56 33 132 99 25

10 49 68 2.35 35 97 62 3611 62 78 2.84 36 136 100 2612 27 70 41

13 57 80 2.71 34 179 145 1914 17 68 3.53 58 152 94 3815 14 96 4.18 44 133 89 3316 56 66 2.12 32 119 87 2717 50 66 2.37 36 171 135 2118 45 72 2.69 37 231 194 1619 38 88 2.39 27 150 123 18

Mean 41 77 2.76 36 140 103 29

Predominant aortic insufficiency20 46 94 1.92 20 143 123 1421 31 72 2.10 29 322 293 922 42 63 2.07 33 114 81 2923 53 63 3.04 48 267 219 1824 20 78 2.76 35 350 315 1025 43 74 1.89 26 144 118 1826 18 84 4.42 53 183- 130 29

8 200/11 90/655 132/9 100/684 224/7 128/80 No

11 216/14 148/54 diastolic12 172/16 116/72 murmur

3 180/3 116/728 160/11 80/54

10 162/18 104/649 124/10 90/52 Murmur3 164/5 140/64 of3 165/7 125/64 aortic

14 220/17 100/52 insufficiency5 196/5 106/60

11 224/18 152/56

4 104/8 120/329 148/14 118/568 108/8 117/62

12 136/18 144/487 116/15 144/444 130/7 164/564 120/6 128/72

75 2.60 35 218 183 18

Mitral stenosis27 23 78 2.98 38 109 71 3528 48 70 2.44 35 125 90 2829 23 69 1.73 25 74 49 3430 35 91 2.63 29 85 56 3431 49 72 2.46 34 189 155 18

Mean 36 76 2.45 32 116

Mitral insufficiency32 56 81 1.63 2033 44 93 2.21 2434 49 82 1.86 2335 44 102 1.99 20

Mean 48 90 1.92 22

28 90/6 120/5612 100/10 114/7622 104/6 112/6418 102/7 114/6411 90/13 120/64

84 30

4 11 96/824 13 128/722 5 124/233 8 110/621

112/68152/72128/80132/80

Mixed valve disease36 51 63 2.12 34 106 72 3237 49 93 2.13 23 177 154 1338 44 86 2.45 29 126 103 23

Mean 48 81 2.23 29 136 110 23

17 182/11 112/54 AS, MS22 160/7 96/62 AS, MS19 120/7 102/60 MS, AS, Al

Mean 36

* EDV = end-diastolic ventricular volume; ESV = end-systolic ventricular volume; FSV = forward or effectivestroke volume; LA = left atrial; LV = left ventricular; BA = brachial artery; AS = aortic stenosis; MS= mitralstenosis; and AI = aortic insufficiency.

t The left ventricular diastolic pressure was measured at end-diastole (at the time of onset of ventricular contrac-tion).

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BRISTOW, CRISLIP, FARREHI, HARRIS, LEWIS, SUTHERLAND,ANDGRISWOLD

e 0.9

q 0.8

t 0.7

2 0.6

t 0.5

c: 0.4

* 0.3

j

I.,

I-

*1IF.

F0 oi47. 0

I-

I-

0.1 -

V/ I I I I I

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9Average TntI /Tn for each curve

FIG. 1. REPRODUCIBILITY OF THE METHOD. The measurement obtainedfrom the thermodilution curves was the ratio TR+ /Tn, as explained in text.This ratio is plotted for each curve against the average for all curves inthat patient. The variability is shown by the scatter on either side of theline of no difference.

l I

5 sec I 5FIG. 2. DUPLICATE THERMODILUTIONCURVESFROM PATIENT 16. A decrease in temperature is inscribed in an

upward direction. Tn+ l/T is 72%o for the curve on the left and 71% for that on the right. The average of seven

curves in this patient was 73% [forward stroke volume (FSV)/end-diastolic ventricular volume (EDV) = 27%o].In the example on the right, injection produced one premature contraction. The electrocardiogram is above.

f

sec

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"7710"

I

I Il1

LEFT VENTRICULARVOLUMEMEASUREMENTSIN MANBY THERMODILUTION

compared to the average for the curve as a per-centage, regardless of sign. In 300 such com-parisons the mean difference was 3.8 ± 3.4 %.These findings are similar to those we obtained ina series of experiments in dogs (9).

The fraction of the EDV ejected as the FSVranged from 27 to 54%o in the five patients with"normal" ventricular f unction (miscellaneousgroup). An example is shown in Figure 3.Low ratios of FSV/EDV and the largest EDV'swere found in the patients with predominantaortic insufficiency (Figure 4). The mean EDVfor this group was 218 ml per m2 BSA, and thisvalue was significantly different from that of themiscellaneous group (p < 0.01). The value forthe ESV and regurgitant volume combined wasalmost three times greater in the aortic insuffi-ciency patients.

The findings in four of the five patients withmitral stenosis were similar to the miscellaneouscategory, and no difference between the groupsfor EDVwas shown (Figure 5).

Patients with predominant aortic stenosis hada larger EDV than the miscellaneous group (p <0.01). Seven of these 13 patients had a murmurof aortic insufficiency, although this lesion was

400 _

300 -

.4N,

200-

0oo -

1 5 secI

FIG. 3. THERMODILUTION CURVE FROM PATIENT 3,CLASSIFIED IN THE MISCELLANEOUSGROUP. T8+ i/T, is46% and FSV/EDV is 54%. The cold (indicator) isvirtually cleared from the ventricle in four beats.

not considered a prominent feature of their dis-ease. These seven had a mean EDV of 162 mlper m2 compared to 113 ml per m2 for those withaortic stenosis and no regurgitant murmur (p <0.01). When those with no aortic insufficiencywere compared with the miscellaneous group, nodifference was found. When the entire aorticstenosis group was compared to those patientswith predominant aortic insufficiency, the latterhad a larger EDV (p < 0.05).

x MiscellaneousOMSA AS - no diastolic murmurA AS- with diastolic murmurA AIo Bivolvulor disease

A

A

0

§ 00

xx 0x 0

AAAA

A D

AAA 0

a

A

FIG. 4. LEFT VENTRICULAREDVIN ALL PATIENTS IN WHOMIT WASMEAS-URED. Abbreviations: MS= mitral stenosis; AS = aortic stenosis; Al =

aortic insufficiency.

1019

BRISTOW, CRISLIP, FARREHI, HARRIS, LEWIS, SUTHERLAND,AND GRISWOLD

5 secFIG. 5. THERMODILUTIONCURVEFROMPATIENT 27, WHO

HADPUREMITRAL STENOSIS. Steplike temperature changesin the upslope of the curve resulted when injection wasnot confined to diastole. This did not influence tempera-ture ratios in the downslope.

The thermal curves were employed empiricallyin the four patients with mitral insufficiency, andventricular EDV was not calculated. Three ofthese four had atrial fibrillation with a fairly reg-ular ventricular rate and were the only ones in thestudy who did not have sinus rhythm. Their val-ues for FSV/EDV tended to be low.

There was a generally inverse relationship be-tween the fraction of the EDV ejected as theFSV and the EDV itself, as shown in Figure 6.Thus when all the patients were compared, theFSV tended to fall or remain unchanged as theEDV increased.

Discussion

The measurements of left ventricular EDVcorrelated well with clinical observations in thepatients studied. In general those with mitralstenosis or pure aortic stenosis had an EDVsimi-lar to the control group, and those with predomi-nant aortic insufficiency had larger volumes, asexpected. The miscellaneous group of five pa-tients all had heart disease, which in four hadbeen treated surgically with good results. It ispossible, or even likely, that more complete sys-tolic emptying of the ventricle and a smaller ESVoccur in persons without heart disease. At pres-ent our data and those of Folse and Braunwald(14), using a somewhat similar approach, sug-gest that the normal EDV is below 150 ml per in2.

An interesting finding in the patients withaortic stenosis was the difference between thosewith and those without, an aortic insufficiency mur-

x Miscellaneouso MSA ASA AIo Bivalvular disease

A0 A

AAA A0A o

A

200EDV (ml/M2)

300

FIG. 6. FRACTION OF THE EDVEJECTED AS THE FSV IS PLOTTED WITH

THE EDV ITSELF. With the larger EDV's FSV/EDV tended to below. See text for discussion.

60

50AX

x

40_t~jN

30_

20_

1OF_

0

A

A A

100 400

I -1 -1 11 . I . --.. I .J - -I , I; Am i I -

0;04 - r -r I- wr wr

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LEFT VENTRICULARVOLUMEMEASUREMENTSIN MANBY THERMODILUTION

A

AA

A

A

0

x Q A

AA A

0 x Ax0kA

0 0

x Ax

A

1000

x Miscellaneouso MSAAS

A Alo Rivalvular disease

0

A

A

200EDV (ml/M2)

300

FIG. 7. LEFT VENTRICULAR END-DIASTOLIC PRESSUREPLOTTED AGAINST

EDV. No correlation is discernible.

mur. In those with the murmur, the amount ofregurgitation was judged to be minimal on thebasis of clinical and hemodynamic evidence. De-spite this, a larger EDV was found as well as a

high value for the ESV and regurgitant volumescombined. Since the total left ventricular strokevolume in the presence of aortic regurgitationcannot be measured by our method, the degree ofsystolic ventricular emptying cannot be deter-mined. However, a larger EDV in the presence-of the regurgitant murmur strongly suggests thatthe regurgitant volume was greater than we wouldhave predicted. Although ventricular failure dueto aortic stenosis would be expected to producethe same findings, we do not believe it explainsthe difference in these patients.

We found no correlation between ventricularEDVand end-diastolic pressure, as shown in Fig-ures 7 and 8. For example, in patients with aorticstenosis and equivalent EDV's, end-diastolic pres-

sure ranged from 3 to 18 mmHg. Normal end-diastolic pressure was found in a few patientswith grossly increased EDV, and high end-dia-

stolic pressure occurred in one patient with a

normal EDV, associated with aortic stenosis.Presumably the muscular hypertrophy which oc-

curs with aortic stenosis can decrease ventriculardiastolic compliance. Because of the variabilityof the end-diastolic pressure when patients are

compared, it seems unwise to diagnose ventricularfailure on this basis alone. \Vork by Dodge, Hay,and Sandler is consistent with this conclusion(15), and a recent editorial has advised a re-

appraisal of the interpretation of ventricular end-diastolic pressure (16).

The generally inverse relation between FSV/EDVand EDVindicates the serious consequences

of valvular heart disease for the left ventricle.To develop a given systolic pressure, a large EDVnecessitates a large increase in the force of con-

traction by the ventricular muscle (17), simplyto produce the same or even a smaller forwardflow. The disadvantage for ventricular functioncan be enormous, and myocardial oxygen needswill be increased (18).

One of the patients with mitral stenosis de-

18

16

14

X,, I 2)%i2:Io-310

8

6

4

400

2

I

1021

2

BRISTOW, CRISLIP, FARREHI, HARRIS, LEWIS, SUTHERLAND,AND GRISWOLD

20-

10-

0-

L A LV

... ...,i.tt I.... ..+

1 e c

LV

I._,,... ..,. .. ..ii....,11....... ..1..._' ._ .., ..k.. .... .. ..

-.

FIG. 8. ABOVE: LEFT ATRIAL AND VENTRICULAR PRES-

SURES IN PATIENT 13 WHOHAS AORTIC STENOSIS. End-diastolic pressure is elevated, as indicated by the arrow,

and is associated with a tall left atrial "a" wave. BELOW:SIMILAR PRESSURESIN PATIENT 26 WHOHAS AORTIC IN-

SUFFICIENCY. The pressures are normal. Despite thewide difference in end-diastolic pressures, both have al-most identical EDV's (179 and 183 ml per m2, respec-

tively).

serves additional comment (Patient 31). Thiswoman had a large EDV, slightly elevated leftventricular end-diastolic pressure, and a lowFSV/EDV. Our other patients with mitral sten-osis and those in the study by Folse and Braun-wald (14) did not exhibit these findings. Thepossibility of primary left ventricular disease as-

sociated with mitral stenosis can be suggested toexplain these abnormalities. Measurement ofleft ventricular volume in mitral stenosis shouldlead to a better understanding of ventricular func-tion in this disease, an area which others havescrutinized (19).

The measurement of ventricular volume has

presented theoretical and technical problems. Twodifferent approaches have been by indicator dilu-tion techniques and by angiocardiography. Inboth methods there are inherent assumptions con-cerning the geometry of the ventricle or the mixingof indicator in it. Although comparison of re-sults in different patient groups studied by variousmethods has some obvious limitations, similarityor difference between results may contribute to abetter understanding of the methods used. Thestudy which is most comparable to the one hereinreported was done by Folse and Braunwald (14).They injected radioactive iodine into the left ven-tricle and measured its clearance with a precordialcounting technique. Our thermodilution resultscompare closely with their findings. Their normalgroup had ratios of FSV/EDV from 29 to 48%,compared with 27 to 54% in our miscellaneousgroup. The calculated EDV's also comparedclosely. In general, the findings with aortic valvedisease were similar in the two studies. The simi-larity of the results and the reproducibility of bothmethods are encouraging.

Several investigators have reported left ven-tricular volume measurements in man obtained byangiocardiography (15, 20-22). In general, theyfound a smaller EDVand a greater FSV/EDV inthe normal left ventricle than was observed in ourmiscellaneous group and the normal group ofFolse and Braunwald's study. A higher FSV/EDV was found in several patients with heartdisease by the angiographic approach than ob-served with the indicator dilution techniques.These comparisons suggest a systematic differ-ence between the results obtained by these twomethods.

Studies of mixing of indicators in the left ven-tricle have been done (23, 24), and the conclu-sion has been drawn that imperfect mixing occursand can introduce errors in the calculations ofventricular volumes. Although this is true, thereare considerations which suggest that serious er-rors do not often occur. The most importantevidence is the consistency of the exponentialwashout of indicator from the ventricle, since in-complete mixing might be expected to produce anonexponential series of aortic indicator concen-trations. Randomly occurring errors of mixingmight also make reproducibility difficult to dem-onstrate. Furthermore, as Holt has pointed out,

1022

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LEFT VENTRICULARVOLUMEMEASUREMENTSIN MANBY THERMODILUTION

perfect ventricular mixing is not required for va-lidity of the method (25). Rather, the series ofdecreasing aortic concentrations must equal a cor-responding series of average ventricular end-diastolic concentrations, whether the indicator iswell mixed or not. A misleading, reasonablypure exponential could occur, however, if bloodentering the ventricle f rom the atrium duringdiastole gained a consistent (but insufficient) pro-portion of residual ventricular indicator and waspreferentially ejected as the next stroke volume.In this situation, the degree of ventricular empty-ing could be underestimated. When empiricalmodels of such situations are constructed mathe-matically, the errors in general do not change theorder of magnitude of the results. The additionof aortic insufficiency to the system might be ex-pected to improve ventricular mixing by turbu-lence in the chamber.

The method we employed was safe, reproduci-ble, and easily performed during the course oftransseptal left heart catheterization. The in-formation obtained was useful in the clinicalevaluation of the patients and in several caseshelped to explain elevated left ventricular end-diastolic pressures that would otherwise havebeen attributed to ventricular failure despitethe absence of any other signs. \Ve believe thatfurther application of the method in study of thecirculation in man is warranted.

Summary

In 38 patients, left ventricular volume estima-tions were obtained from thermodilution curvesrecorded in the ascending aorta after left ventricu-lar injection of cooled saline. The results werereproducible, and a discontinuous, steplike ex-ponential function was consistently seen in thethermodilution curves.

Patients without significant abnormalities of leftventricular function were compared with groupswith various valve lesions. These with "normal"ventricular function, with mitral stenosis, andthose with pure aortic stenosis had similar end-diastolic ventricular volumes. Patients with aorticstenosis and the murmur of aortic insufficiencyhad larger volumes as did those with predomi-nant aortic insufficiency.

There was no correlation between end-diastolic

volume and ventricular end-diastolic pressure whenpatients were compared.

It is concluded that thermodilution offers a safemeans of obtaining left ventricular volume estima-tions during left heart catheterization and that theinformation obtained is useful for clinical andinvestigative purposes.

References1. Fegler, G. Measurement of cardiac output in anes-

thetized animals by a thermodilution method.Quart. J. exp. Physiol. 1954, 39, 153.

2. Goodyer, A. V. N., A. Huvos, W. F. Eckhardt, andR. H. Ostberg. Thermal dilution curves in theintact animal. Circulat. Res. 1959, 7, 432.

3. Evonuk, E., C. J. Imig, W. Greenfield, and J. W.Eckstein. Cardiac output measured by thermaldilution of room temperature injectate. J. appl.Physiol. 1961, 16, 271.

4. Hosie, K. F. Thermal-dilution technics. Circulat.Res. 1962, 10, 491.

5. Rapaport, E., and B. D. Wiegand. Estimation ofleft ventricular volume by the thermodilutionmethod. Clin. Res. 1961, 9, 85.

6. Thorpe, C. R., and F. S. Grodins. Estimation ofleft ventricular volumes from thermodilutioncurves. Fed. Proc. 1960, 19, 117.

7. Rapaport, E., B. D. Wiegand, and J. D. Bristow.Estimation of left ventricular residual volume inthe dog by a thermodilution method. Circulat.Res. 1962, 11, 803.

8. Bristow, J. D., R. E. Ferguson, F. Mintz, and E.Rapaport. Thermodilution studies of ventricularvolume changes due to isoproterenol and bleeding.J. appl. Physiol. 1963, 18, 129.

9. Bristow, J. D., R. E. Ferguson, F. Mintz, and E.Rapaport. The influence of heart rate on leftventricular volume in dogs. J. clin. Invest. 1963,42, 649.

10. Eckstein, J. W., and M. G. Wendling. Effects ofhexamethonium (C6) and norepinephrine (NE)on left ventricular end-diastolic and end-systolicvolumes (abstract). Clin. Res. 1963, 11, 165.

11. Rapaport, E., M. Wong, R. E. Ferguson, P. Bern-stein, and B. D. Wiegand. Right ventricular vol-umes in patients with and without heart failure.Fed. Proc. 1963, 22, 402.

12. Brockenbrough, E. C., E. Braunwald, and J. Ross,Jr. Transseptal left heart catheterization. Areview of 450 studies and description of an im-proved technic. Circulation 1962, 25, 15.

13. Holt, J. P. Estimation of the residual volume of theventricle of the dog's heart by two indicator dilutiontechnics. Circulat. Res. 1956, 4, 187.

14. Folse, R., and E. Braunwald. Determination offraction of left ventricular volume ejected per

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BRISTOW, CRISLIP, FARREHI, HARRIS, LEWIS, SUTHERLAND,AND GRISWOLD

beat and of ventricular end-diastolic and residualvolumes. Experimental and clinical observationwith a precordial dilution technic. Circulation1962, 25, 674.

15. Dodge, H. T., R. E. Hay, and H. Sandler. Pres-sure-volume characteristics of the diastolic leftventricle of man with heart disease. Amer. HeartJ. 1962, 64, 503.

16. Braunwald, E., and J. Ross, Jr. The ventricularend-diastolic pressure. Appraisal of its value inthe recognition of ventricular failure in man.

- Amer. J. Med. 1963, 34, 147.17. Burton, A. C. The importance of the shape and

size of the heart. Amer. Heart J. 1957, 54, 801.18. Levine, H. J., and R. J. Wagman. Energetics of

the human heart. Amer. J. Cardiol. 1962, 9, 372.19. Harvey, R. M., M. I. Ferrer, P. Samet, R. A.

Bader, M. E. Bader, A. Cournand, and D. W.Richards. Mechanical and myocardial factors inrheumatic heart disease with mitral stenosis.Circulation 1955, 11, 531.

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21. Sandler, H., H. T. Dodge, R. E. Hay, and C. E.Rackley. Quantitation of valvular insufficiencyin man by angiocardiography. Amer. Heart J.1963, 65, 501.

22. Bunnell, I. L., D. Ikkos, U. G. Rudhe, and H. J. C.Swan. Left-heart volumes in coarctation of theaorta. Amer. Heart J. 1960, 61, 165.

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