An Angiocardiographic Method for Directly Determining Left Ventricular Stroke Volume in Man
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1 An Angocardographc Method for Drectly Determnng Left Ventrcular Stroke Volume n Man By Harold T. Dodge, M.D., Robert E. Hay, M.D., and Harold Sander, M.D. n prevous studes from ths and other laboratores, rapd bplane angocardography has been utlzed to quantfy left ventrcular chamber volume and volume changes n man and expermental anmals. " 9 Arvdsson 2 measured left ventrcular stroke volume n several subjects wth valvular heart dsease n the course of extensve studes on left atral volume changes, and Chapman and coworkers 3 ' 4 determned left ventrcular volume curves and stroke volume n cannes and a normal man usng a bplane cneangocardographc technque. Others have utlzed a sngle-plane technque to determne left ventrcular volume n expermental anmals. 0 " 2 The valdty of correctons for x-ray dstorton and of calculatons of volume from bplane x-rays has been demonstrated usng models 3 ' 5 and contrast-flled postmortem hearts. 5 Recently, Arvdsson compared left ventrcular mnute volumes determned by an angocardographc method wth mnute volumes determned by the Fck method and found close agreement n the majorty of subjects. 8 n hs studes, angocardography was performed under condtons of general anesthesa and postve ntrathoraec pressure. n the present study, stroke volumes determned from bplane angocardograms were compared wth stroke volumes determned by Fck and ndeator- From the Medcal Servce of the Veterans Admnstraton Hosptal, and the Department of Medcne, Unversty of Washngton School of Medcne, Seattle, Washngton. Ths work was supported n part by Grant H-339 (C4), U. S. Publc Health Servce, and by the Washngton State Heart Assocaton. Dr. Sander s a Post-Doctoral Research Fellow, Natonal Heart nsttute, U. S. Publc Health Servce. Receved for publcaton March 2, 962. Crculaton Research, Volume X, October 00 dluton technques. The physologcal state of the patent just pror to angocardography was smlar to that present at the tme of the Fck and ndcator-dluton cardac output determnatons. These studes were reported earler n prelmnary form. 9 Methods Fourteen adult male subjects wth pulmonary or cardac dsease, as ndcated n table, were selected for study after clncal examnaton revealed no evdence of congental cardac defects, valvular nsuffcency, or arrhythma. All were studed n the restng, recumbent, fastng state. Sodum pentobarbtal, 00 mg., was gven orally or ntramuscularly 30 to 60 mnutes before the start of the procedure. An ndwellng needle was placed n a brachal artery, a no. 9 angocardographc catheter was passed va an anteeubtal ven to the pulmonary artery, and duplcate cardac outputs were determned by the drect Pck technque. The heart rate was recorded durng each of the collecton perods. Duplcate cardac outputs were then determned by the ndcatordluton technque wth a cuvette denstometer 3 and drect-wrtng recorder, usng Evans blue dye wth pulmonary arteral njecton and brachal arteral samplng. Detals of the Fck and ndcator-dluton technques as used n ths laboratory have been prevously descrbed. 4 The catheter was wthdrawn so that ts tp was near the juncton of the superor vena cava and the rght atrum. Contrast medum, 40 to 50 cc. (0.65 to.5 cc.kg. of 70 per cent sodum acetrzoate'), was njected through the catheter by a Gdlund power syrnge at a pressure of 4 Kg. per cm. 2. One and one-half to three seconds were requred for the njecton. Subjects were nstructed to contnue quet breathng durng flmng. By means of a Schonander bplane x-ray unt, flms were exposed n the anteroposteror and left lateral projectons at the rate of four to sx flms per second for a perod of from fve to seven seconds. The duraton of each exposure Urokon, Mallnckrodt Chemcal Works, New York Cty. 739
2 740 DODGE, HAY, SANDLER 60 x y UJ 20 6 > X 80 A \ % X». ' X r «' * 40 d = 0 EC* FGURE ventrcular chamber volume plotted wth respect to tme of x-ray exposure as ndcated on the upper channel of the recordng. was 0.03 to 0.04 second at 300 to 400 ma. and 00 to 20 kv. The tme to actvate the flm changer, n order to obtan a maxmum number of x-ray exposures durng left ventrcular opaefcaton, was ascertaned from the prevously recorded ndcator-dluton curves. A photo-cell recorded on a drect-wrtng multchannel recorder the tme of exposure of each par of flms wth respect to the electrocardogram and brachal arteral pressure (fg. ). n one subject, the angoeardographc examnaton was repeated approxmately 30 mnutes after the ntal examnaton because of malfuncton of the flm changer. CALCULATONS For purposes of volume calculaton, t was assumed that the left ventrcular chamber could be represented as an ellpsod fgure and volume calculated by usng the formula for the volume of an ellpsod : V = - where V = volume, lm = length of the major axs, and d', d" = the lengths of the two mnor axes. The above axes were determned as follows: The margns of the opacfed left ventrcular chamber were drawn on each set of flms and transferred to tracng paper. n each projecton, the area of the left ventrcular chamber was determned by planmetry and the maxmum length of the chamber measured drectly. The transverse chamber dameters n the anteroposteror and lateral projectons were calculated from the followng ellpse formula: lm 4A (2) where d = transverse chamber dameter n a gven projecton, A = area of the chamber n the projecton, and = maxmum length of the chamber n the projecton. Each of the above dameters was corrected for x-ray dstorton from knowledge of x-ray tube-to-flm dstances, whch were measured, and left ventrcle-to-flm dstances, whch were calculated from the relatonshp of the left ventrcle to the central x-ray beam of each tube, whch was recorded on each flm.5 n calculatng chamber volume, the two transverse dameters and the longest drectly measured length, followng correcton for x-ray dstorton, were used. These methods have been descrbed n greater detal elsewhere and tested on human postmortem hearts, wth establshment of a regresson equaton relatng known to calculated volumes together wth the standard error of estmate of the method.5 n the present -study, the volumes were all corrected, usng the regresson equaton determned n the prevous study :5 V = V 3.S (3) where V = corrected volume n cc, and V = volume calculated by applyng equaton. Bach volume determnaton was plotted at the pont correspondng to ts tme of exposure on the recordng strp, as shown n fgure. Each determnaton was then tmed wth respect to the onset of the QRS complex of ts partcular heart cycle, and fnally, all determnatons were combned on the bass of tme from the onset of the QRS to form a sngle composte volume curve (fg. 2). These composte curves were made up of from eght to 26 observatons (mean 7) obtaned durng the two to eght heart cycles selected on the bass of adequate opacfcaton of the left ventrcular chamber and freedom from evdent physologcal effects of the njecton or the contrast materal. The ponts of maxmum and mnmum volume on the composte curve represented the end-dastolc and end-systolc volcrculaton Research, Volume X, October 962
3 STROKE VOLUME BY ANGOCARDOGRAPHY 74 TABLE Comparson of Stroke Volumes Determned by Angocardographc, Fck, and Bye-Dluton Methods Patent.W. C.S. A.X. H.B. J.T..M. W.H D.W H.H. H.S. M.H. F.P..T.E. B.N. Fck Dagnoss CO HR sv dopathc cardomyopathy dopathc cardomyopathy Bronchogenc carcnoma Bronchogenc carcnoma Bronchogenc carcnoma Bronchogenc carcnoma Bullous emphysema Pulmonary nfltrate? etology 4.9 : L04 dopathc cardomyopathy Bronchogenc carcnoma Pulmonary embol : no Hypertenson Mtral stenoss Aortc stenoss samples ± SD: Mean dfferences of pared Dye 2.3 ± 8. cc. > Ango 3.5 ± 7.6 cc. > Ango. ± 5.0 cc. > Ango 2.3 ± 5.2 cc. > Fck, or 7.3 ± 6% of Fck* Fck, or 8.0 6% of Fck dye, or. 8.2% of dye average of Fck and dye, % of average Fck and dye *Per cent dfference relates dye-fck ango dye ; ngo Fck Fck dye Fck umes, respectvely. There were usually several volume determnatons at end-systole and end-dastole, and n no nstance was t necessary to use a sngle volume determnaton n defnng these ponts on the curve. The stroke volume was then calculated by subtractng the end-systolc from the end-dastolc volume. The relatvely slow rate of flmng, whch requred the use of a volume curve constructed from volume observatons durng several heart beats, was ordnarly satsfactory. Occasonally, however, the heart rate and rate of flmng were suffcently synchronous so that no observatons were obtaned at end-systole or end-dastole, and then stroke volume could not be determned by ths method. Crculaton Research, Volume X, October 902 CO S S Dye HR sv Average Fck and dye SV CO = HR = SV = EDV = ESV EDV Ango< :ardography ESV SV HR cardac output heart rate stroke volume end-dastolc volume end-systolc volume Results S CO 4.3? The measurements of stroke volume obtaned by the varous methods are lsted n table and compared graphcally n fgure 3. The mean stroke volumes of the dfferent subjects ranged from 32 to 0 cc. and enddastolc volumes from 49 cc. n subject H.S. to 345 cc. n subject C.S. An attempt was made to nclude subjects who demonstrated dfferng levels of both stroke volume and end-dastole volume. Two of the subjects d.w. and C.S.) had moderate and marked
4 742 DODGE, HAY, SANDLER Seconds after onset of QRS FGURE 2 Composte volume curve constructed from data n fgure. left ventrcular dlataton, respectvely, and two others had end-dastole volumes that were larger than normal. 8 Although there were few stroke volume determnatons at any gven dastolc volume, the agreement between the methods seemed smlar at the varous volumes represented. n eght of subjects, the stroke volumes determned by the Fck method were smaller than those determned angocardographcally. The mean algebrac dfference between the two methods, however, was only ± 7.6 cc. Ths dfference was not statstcally sgnfcant n the number of cases studed. A smlar, although smaller, dfference was obtaned between stroke volumes determned by the Fck and the ndcator-dluton methods and the ndcator-dluton and the angocardographe technques. n table and fgure 3, the mean of the Fck and ndcatordluton determned stroke volumes has also been compared wth the angoeardographeally determned stroke volumes n an attempt to avod the extremes of varaton n the Fck and dye-dluton methods. 8 " 7 Observatons of heart rate, rhythm, and arteral pressure from the tme of njecton of contrast materal through the perod of flmng demonstrated changes n some subjects. A premature beat durng the njecton, whch was usually several seconds pror to flmng of the left heart, was occasonally observed. n 0 of the subjects, varyng degrees of hypotenson and bradycarda developed after most or all of the flmng was completed. Of the remanng four subjects, one (A.N.) experenced a 20-mm. Hg fall n systolc blood pressure durng flmng. n another (B.N.), bradycarda was noted, the heart rate decreasng from 00 to 80 per mnute. Two others (J.E. and.m.) had mld bradycarda and a 0-mm. Hg fall n blood pressure. n spte of these physologcal changes, n each nstance the angocardographeally determned stroke volume was smlar to that determned earler by the Fck and ndcator-dluton technques. Dscusson Angrocardosrraphy has been used extensvely n physologcal and dagnostc studes n expermental anmals and man, but the observatons, wth a few exceptons, have been qualtatve or semauanttatve. Prevous studes have been performed on models and postmortem hearts to develop and test methods for quantfyng left ventrcular chamber volume from bplane flms of the opaefed left ventrcular chamber. 3 ' 5 Grbbe demonstrated a close correlaton between left ventrcular stroke volumes calculated from sngle-plane angocardograms and stroke volumes determned by the Fck method n expermental anmals. 2 n a recent study, Arvdsson found close agreement between left ventrcular mnute outputs determned from bplane aneocardosrams and cardac outputs determned by the Fck method. 8 Ths agreement n results prevaled n spte of the fact that the angocardographc observatons were made durng general anesthesa and nduced Crculaton Research, Volume X, October 962
5 STROKE VOLUME BY ANGOCARDOGRAPHY 743 postve ntrathoracc pressure, a dfferent physologcal state from that exstng at the tme of the Fck cardac output determnatons. n studes where angocardography has been used as a quanttatve method, there has been uncertanty about the effects of the sudden njecton of a volume of contrast materal, the contrast materal tself, the varyng degrees of left ventrcular opacfcaton, and the varyng confguratons of the left ventrcular chamber on calculated ventrcular volume and volume changes. Accordngly, t has been uncertan to what extent data obtaned by angocardographc technques are comparable wth data obtaned by other methods. The comparson of stroke volume, as determned by three ndependent methods n these subjects wthout clncal evdence of valvular nsuffcency, has provded an n vvo test of the angocardographc method for determnng left ventrcular volume changes. Testng of the n vvo determnaton of absolute left ventrcular chamber volume must awat development of a sutable alternatve method for determnng ths volume. n the group as a whole, stroke volume as determned by the Fck, ndcator-dluton, and angoeardographc methods agreed closely. However, n an occasonal subject, such as W.H. (table ), stroke volumes determned by these ndependent methods were consderably dfferent. Whether these dfferences were due to changes n the physologcal state of the patent or to problems nherent n the methods for determnng stroke volume was not defned. Table 2 contans a summary of publshed work by others relatng stroke volumes determned by Fck and ndcatordluton methods. t s of nterest that the mean dfferences and standard devatons of stroke volumes determned by these two methods n earler studes were smlar to those observed n the present study. n each of these earler studes, farly large dfferences n stroke volumes as determned by these two methods were occasonally observed, n spte Crculaton Research, Volume X. October _2 80-f o y O > ^ x 0 X O * x *> % o >. O Fck Stroke Volume y a <D o E o>_3.2 o * f O * * x 8"o x x x u t x > "... "» X * s-s "» «" < Fck Stroke Volume»* u a. o o E 0.-2 oo ~ > X 5_ * «o S * Fck+Dye Dye Stroke Volume o><^ 2 "* Stroke Volume CC FGURE 3 Comparson of stroke volumes as determned by the Fck, ndcator-dluton, and angocardographc methods. of the fact that the determnatons were performed more or less smultaneously. These dfferences have been ascrbed, n part, to a summaton of the techncal dffcultes nherent n the two methods. 7 n the present study, left ventrcular stroke volume determned by the angocardographc method correlated wth the stroke volume determned by the Fck and dye-dluton methods as well as or better than the Fck and dyedluton determned stroke volumes correlated wth one another. t s of note that ths angocardographc method provdes a method for drectly determnng left ventrcular stroke volume n man. The Fck and ndcator-dluton technques, as usually appled, provde a measure of mean pulmonary, or systemc, blood flow per stroke. Although under normal condtons these flow values and left ventrcular output are equal, left ventrcular output may dffer from these flow values n subjects wth valvular nsuffcency or certan cardac shunts. The dfference between left ventrcular stroke volume determned by the angocardographc method and the stroke volume determned by the Fck or ndcator-dluton methods has
6 744 DODGE, HAY, SANDLER TABLE 2 Comparson of Stroke Volumes Determned by the Fck and ndcator-dluton Methods from Data Publshed by Others Seres Number of observatons Hamlton et al Werko et al." 66 Kopelman and Lee 0 28 *Per cent dfference relates dye-fck Fck Mean dfferences of pared samples + SD Maxmum dfference* Dye.7 ± 2.5 ce. > Fck or 2.6 ± 8.% of Fck* 46% Dye 3.7 ± 2.7 cc. > Fck or 7.8 ± 8.2% of Fck 52% Dye 0.2 ± 6.2 cc. > Fck or 0.9 ± 0.4% of Fck 37% been used to quantfy aortc and mtral valvular nsuffcency. 8 One of the most mportant problems n quanttatve angocardography s concerned wth obtanng satsfactory left ventrcular opacfcaton wth a mnmum of untoward cardovascular reactons. Unfortunately, both the degree of opacfcaton and the severty of reactons seem drectly related to the volume and concentraton of contrast materal. To apply ths quanttatve angocardographc method requres flms that demonstrate an opacfed left ventrcle wth margns that can be defned and traced. Experence n ths laboratory ndcates that n subjects wth marked heart enlargement or marked valvular nsuffcency, t s often not possble to obtan ths degree of left ventrcular opacfcaton wth rght heart njectons of the amounts of contrast materal used n ths study. The chef cardovascular reactons seen n ths study were premature contractons, extrasystoles, bradycarda, and hypotenson, whch are common durng angocardography and are descrbed n some detal by others. 9 " 23 Wth respect to the quanttatve aspects of angocardography, the tme sequence of these phenomena s of some mportance. When rght-sded njectons are used, the arrhythmas occur durng the actual moment of njecton, several seconds pror to flmng of the left heart. Bradycarda and hypotenson, when present, are usually noted as the contrast materal leaves the left ventrcle and follow left ventrcular opacfcaton. 4 ' 2 Others have found that left ventrcular stroke volume remans relatvely constant pror to the appearance of bradyearda and hypotenson. 4 ' 2 Ths observaton was also made n the present studes when suffcent flms were avalable and the tmng of flm exposure made possble stroke volume determnatons of ndvdual beats. Summary A method has been descrbed for drectly determnng left ventrcular stroke volume n man through the use of bplane angocardography. Left ventrcular stroke volume determned by ths method has been compared wth stroke volumes determned by the Fck andor ndcator-dluton methods n 4 subjects wthout arrhythmas or clncal evdence of valvular nsuffcency. Stroke volumes determned by these varous methods showed close agreement. Acknowledgment The authors express ther apprecaton to Mss nara Stenhards and Mrs. Joan McGlton for valuable techncal assstance. References. DODGE, H. T., AND TENENBAUM, H. L.: Left ventrcular volume n normal man and alteratons wth dsease. Crculaton 4: 927, ARVDSSON, H.: Angocardographc observatons n mtral dsease, wth specfc reference to volume varatons n the left atrum. Acta radol. (suppl.) 58:, CHAPMAN, C. B., BAKER, 0., REYNOLDS,J., AND BONTE, F. J.: Use of bplane cnefluorography for measurement of ventrcular volume. Crculaton 8: 05, CHAPMAN, C. B., BAKER, O., AND MTCHELL, J. H.: Left ventrcular functon at rest and durng exercse. J. Cln. nvest. 38: 202, DODGE, H. T., SANDLER, H., BALLEW, D. H., AND LORD, J. D., JR.: Use of bplane angocardography for the measurement of left ventrcular volume n man. Am. Heart J. 60: 762, 960. Crculaton Research, Volume X, October 962
7 STROKE VOLUME BY ANGOCARDOGRAPHY HAY, E. E., SANDLER, H., AND DODGE, H. T.: Eclatonshps of left ventrcular fllng pressure to end-dastolc volume n man wth heart dsease. Cln. Eesearch 9: 62, BUNNELL,. L., KKOS, D., EUDHE, U., AND SWAN, H. J. C.: Left heart volumes n coarctaton of the aorta. Am. Heart J. 6: 65, ARVDSSON, H.: Angocardographe determnaton of left ventrcular volume. Aeta radol. 56: 32, HAT, E., SAXDLER, H., AND DODGE, H. T.: Evaluaton of an angocardographc method for determnng left ventrcular stroke volume n man. Cln. Eesearch 9: 39, GAUER, O. H.: Volume changes of the left ventrcle durng blood poolng and exercse n the ntact anmal: Ther effects on left ventrcular performance. Physol. Eev. 35: 43, GRBBE, P., HRVONEN, V., LND, J., AND WEGELUS, C.: Cneangocardographc recordngs of the cyclc changes n volume of the left ventrcle. Cardologa 34: 348, GRBBE, P.: Comparson of the angocardographc and drect Fck methods n determnng cardac output. Cardologa 36: 20, SHADLE, O. W., FERGUSON, T. B., GREGG, D. E., AND GLFORD, S. E.: Evaluaton of a new cuvette denstometer for determnaton of cardac output. Crculaton Eesearch : 200, DODGE, H. T., LORD, J. D., JR., AND SANDLER, H.: Cardovascular effects of soproterenol n normal subjects and subjects wth congestve heart falure. Am. Heart J. 60: 94, 960. Book Revew 5. WERKO, L., LAGERLOF, H., BDCHT, H., WEHLE, B., AND HOLMGREN, A.: Comparson of Fck and Hamlton methods for determnaton of cardac output n man. Scandnav. J. Cln. & Lab. nvest. : 09, KOPELMAN, H., AND LEE, G.: ntrathoracc blood volume n mtral stenoss and left ventrcular falure. Cln. Sc. 0: 383, HAMLTON, W. F., et al.: Comparson of Fck and dye njecton methods of measurng cardac output n man. Am. J. Physol. 53: 309, SANDLER, H., AND DODGE, H. T.: Quanttaton of valvular nsuffcency by angocardography n man. Cln. Eesearch 8: 9, HLBSH, T. F., AND HERDT, J. E. L.: Complcatons of selectve angocardography. Eadology 75: 97, GORDON, A. J., BRAHMS, S. A., MEGBOW, S., AND SUSSMAN, M. L.: Expermental study of the cardovascular effects of Dodrast. Am. J. Eoentgenol. 64: 89, BJORK, V. O., LODN, H., AND MALERS, E.: Evaluaton of the degree of mtral nsuffcency by selectve left ventrcular angocardography. Am. Heart J. 60: 69, DEYRUP,. J., AND WOLCOTT, W. W.: Mechansm of vagal cardac slowng followng ntravenous njecton of small volumes of strongly hypertonc soluton. Am. J. Physol. 54: 336, MURHEAD, E. E., LACKEY, E. W., BUNDE, C. A., AND HLL, J. M.: Transent hypotenson followng rapd ntravenous njecton of hypertonc solutons. Am. J. Physol. 5: 56, 9. Functonal Behavor of the Mcrocrculaton, Benjamn W. Zwefach, Ph.D. Sprngfeld, llnos, Charles C Thomas, 96, 63 pages, llustrated. $7.00. n the preface, the author rghtfully calls the reader's attenton to the fact that the only authortatve treatse on the blood capllares s stll the monograph by August Krogh, frst publshed n 926. The present monograph adequately flls the need for a bref monograph coverng the functonal behavor of the capllares. The structural bass, vascular reactvty, capllary permeablty, tssue njury, and expermental shock are dscussed n ndvdual chapters. The regonal consderatons of the capllares are lmted to the skeletal muscle, skn, mesentery, and kdney. The lung has been omtted entrely, except to menton ts role n gaseous equlbrum (page 35), ts few dscrete arterovenous thoroughfares (page 22), and endothelal phagocytes (page 48). Ths shortcomng can be overlooked n favor of a clear exposton of the systemc capllares. Crculaton Research, Volume X, October B6
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