the use of fiberoptics in clinical cardiac catheterization

The Use of Fiberoptics in ClinicalCardiac Catheterization

I. Intracardiac Oximetry

By WALTER J. GAMBLE, M.D., PAUL G. HUGENHOLTZ, M.D.,R. GRIER MONROE, M.D., MICHAEL POLANYI, PH.D., AND

ALEXANDER S. NADAS, M.D.

B LOOD oxygen saturation, or content, haslong been measured at cardiac catheteri-

zation to establish the presence of cardiacshunts. For this purpose, a method for accu-rate, immediate, and continuous recording ofintracardiac blood oxygen saturation is theultimate goal.While the Van Slyke method1' 2 remains the

standard technic of measurement, spectropho-tometric analysis3 has gradually found generalacceptance, since it is rapid, reliable, and onlysmall blood samples are needed. More re-cent objections, that the withdrawal of mul-tiple samples may constitute a significantblood loss, and that their analysis remainstime consuming, have spurred application ofcuvette oximetry by the principle of reflectionor transmission.4-6 This permits rapid analysisof the oxygen saturation of unhemolyzedblood, which may then be returned to thepatient. Various instruments, either attachedto the catheter4' 5or used in the catheteriza-tion room6 have indeed reduced the time de-lay between sampling and report. Difficultieswith adequate sampling through the smallcatheters used in infants and children, or withclotting in the cuvette-chamber have keptthese instruments from being universally ac-cepted. Polarographic methods have been de-

From the Cardiopulmonary Laboratory, Children'sHospital Medical Center; the Department of Pedi-atrics, Harvard Medical School, Boston, Massachu-setts.

Supported in part by Grants STI HE 5310-05,1-F3-HE-24 433-01, and HE-6144 from the NationalHeart Institute, U. S. Public Health Service, and byGrant 644 from the Western Chapter of the Massa-chusetts Heart Association.

328

veloped, but likewise have not been entirelysatisfactory because of instability or slow re-sponse of the instrument.7-10 Another draw-back inherent in all these methods is that asample represents an average obtained overvarying time intervals and over varying phasesof systole and diastole.The development of a fiberoptic technic in-

corporating instantaneous as well as continu-ous measurement of oxygen saturationl-13without withdrawal of blood samples consti-tutes a major step forward. Furthermore, thesame catheter and instrument can also be usedto record dye-dilution curves for determina-tion of cardiac output.12 14 The rapid responsetime of such an instrument permits analysisof "step function" for cardiac volumes and anestimation of valvular regurgitation.The principles basic to the technic are de-

scribed briefly. Pulses of light, at 805 and660 m,u, are sent through a fiberoptic bundlewithin the catheter to the blood at its tip. Theback scattered and diffusely reflected light ispicked up by a second bundle of fibers withinthe catheter. The ratio of the intensities ofthese 805- and 660-mu lights so collected hasbeen shown to be a linear function of oxygensaturation.7 The present technic differs fromthat of Enson and co-workers13 in an im-proved design of the catheter tip to avoidartifactual changes in oxygen saturationcaused by proximity of the catheter tip to theendothelial surface, and in the incorporationof an automnatic device which computes theratio of the light intensities and reports theoxygen saturation in as little as 0.07 second.The application of this improved technic ofintracardiac reflection spectrophotometry in a

Circulaton, Volume XXXI, March 1965

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FIBEROPTICS FOR INTRACARDIAC OXIMETRY

clinical cardiac catheterization laboratoryforms the substance of this report.

Material and MethodsAll studies were carried out at the Cardiopul-

monary Laboratory of the Children's HospitalMedical Center, Boston, Massachusetts. In 37patients undergoing cardiac catheterization for a

variety of lesions (table 1), studies with thefiberoptic hemoreflection technic were carried outin addition to the conventional procedures neces-

sary to establish the diagnosis. In 31 patients,oxygen saturations were determined by means ofthe fiberoptic technic. In 19 of these, intracardiacoxygen saturation was measured in vivo simul-taneously with the sampling of blood through a

separate catheter whose tip was located in theimmediate vicinity of the fiberoptic catheter.These samples were analyzed in vitro by spectro-photometric method. Details of the spectrophoto-metric method for analysis of oxygen saturationhave been given previously,3 as have details re-

garding the measurement of intracardiac pres-

sures and other procedures used to establish thediagnosis.15The patients' ages ranged from 7 months to 47

years, values for hematocrit from 28 to 65 per centand for hemoglobin from 8.8 to 24.8 Gm./100 ml.Two types of instruments were employed.* The

first, with a response time in the order of 1.5seconds, is shown schematically in figure 1. Itsdesign is similar to that described by Enson andco-workers,'2' 13 with some modifications.The output from the photocell, which receives

30 pulse pairs of light per second is electronicallyswitched into two channels corresponding to thetwo wave lengths used. These are fed into an

electro-mechanical ratioing device, the output ofwhich (the ratio of light intensities 805 m,t/660m,u) is directly proportional to the oxygen satura-tion.1' This in turn can be fed into conventionalrecorders for simultaneous registration with pres-

sures, electrocardiogram, heart sounds, and otherphenomena.The second instrument has a response time of

0.07 second, and is similar in its principal com-

ponents to the first, except that unfiltered whitelight is conducted to the blood by the efferentfiberoptic bundle. The reflected light, picked up

by the afferent bundle is divided into 540 pulsepairs/second by a rapidly rotating glass diskwith alternate clear and mirrored areas near itsrim. The clear areas allow the beam to pass to a

660-m,u filter, while the mirrored areas reflectthe light to an 805-myi filter. The light passing

Figure 1

Schema of the low-speed instrument. Collimated lightfrom the Tungsten lamp at the upper left, passes

alternately through the two filters mounted on thewheel, then through an optical wedge, and on to theeferent fiber bundle. Light returning from the bloodis carried to the photocell by the afgerent fiberopticbundle. The photocell output, shown on the smallcircle, is divided by the electronic switching circuitand the two outputs are fed to the ratioing device atthe lower left.

each of these filters falls on the same photomulti-plier tube. An optical wedge in the path of the805-m,u filter allows adjustment of the ratio of thelights. The output of the photomultiplier circuit istreated in the same manner as in the first instru-ment, except that the ratioing device is entirelyelectronic and has a very rapid response time(0.07 second). A change in the ratio of lightscauses a deflection in less than 0.01 second.The catheters used in this study were size no.

6F except at the distal tip, where the metallicelement enlarges to a size no. 7F. They are con-

structed from standard Lehman catheterst andcan be sterilized by autoclaving. These catheterscontain two similar bundles of 150 singly cladoptical fibers each measuring 50 ,u in diameter.These afferent and efferent bundles are inter-mixed at the polished distal end where they are

exposed to the blood (thus both bundles subtendthe same solid angle of diffusing blood). Contactwith the walls of the vessel or endocardium isavoided by either of two devices that preventerroneous readings from light reflected from thewalls: The first is a tripod-like structure; thesecond device is similar but in addition has a

tapered, extremely flexible tip which extendsanother 20 to 25 mm.* (fig. 2). This latter design

tU. S. Catheter and Instrument Corporation, GlensFalls, New York.

*Fiber Optics Catheter, C.H.M.C. type.*Both were on loan from the American Optical

Company, Soutlibridge, Massachusetts.

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GAMBLE ET AL.

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1' IBERL)PTICS F0191 INTI ACAliDIAC OXINIET1RY

pi ovedl to be 1)o 110o1e1 irritating to the eCiClo-cardiuns than c()nvenltiollal Lehman catheters. Thetoriu-er, witih the tripod-like pi-otective tij) caIIseda moderate increase in the number of pri ittiaurebeats stim-riiulated l)x manipulation. While theseconl(1 desigii has made mainiaipilatioii (f thefiberoptic catheter safe, the flexible tip (li(l notalways permit the operator to follow a stirearm ofhigh saturation to its origini to locate (or piassthroi.gh ai septal dlefect. This was more easilx(lonie with the tripod tip.

Clottinig has niot beeni a problem with thesecatheters. They were siliconiizedi after each useprior to auitoclavincg in ani eclort to r-educe clotting.Sm-iall fibrinl deposits hatve beeni nioted in 24 peicent of uises, buit n-ever sufficienit to caiuse erro-lleoous readings. These deposits xere on the imetalparts, never on the fiberoptic buLndles. The dep-ositioni of the fibrin seems to bear little correlationito the timne in the blood, as catheters have re-maiined in for 1'2 hours without any fibrin depos-its. On the other hand, fibrin has been picked upby the same catheters in as little as 4 minuLites.A wir-e from the metal parts at the catheter

tip, passing thlrough the catheter to a proximnalterminial, pernmits milonitorinig of the isntracar-diacelectrocardiogram and thlius providles ani additionaliln(licatioi] of the positioni of the tip of the catlhe-ter. 1" At presenit, these catheters do niot permitthe meaisuiremnenit of pressiire. A prelinmiinaryv mo-del tinder studv (fig. 2(C) includ(les a Ilumenileiandhas perimitted the simuiltaneous n easurem-nent ofpressure.

CalibrationSterilized inilk of magniesia, obtainel froin

a single commercial lot, provides a reflectionstandard and is uised in place of blood tostanidardlize the instrumenct (for a givein cathe-ter). This sublstance has a fixed apparenit"saturation," which wx ill, hoxvever, differ bc-tweeu inidividiual catheters diue to small differ-ences in their optical properties. With thecatheter tip in. the milk of magnesia, adjust-meat of the optical xvedge setting regilatesthe otitptut of the ratioiing device to give thisa proper predetermined "saturation." A l)1uefilter may be inserted in the liglht path toclanige the ratio of thb 805 to 660 rnic lighlt,thereby clhaniging the apparent "saturation" bya stanidard amiouniit. This permlits a check on

the gain of the svstem. Prior to inisertioni in thli

tThie catheters were soaked 2 miInutes in a 1:20dilution of Siliclad (Clay Adams, Inc.).

Crcrulatzon, Volume XXXI, Mat-ch 196-5

C

Figure 2Protcctivcd(cices ont thci catheter-setnsioLg elementets.A. C.II.M.C. type wvith distail flexible tip). B. Tripodvariety. C. Cotncenttric pressure-sensing type. A sniallerno.-41L, catheter containiing the fiberoptics is containedlwitlhin a no.-8 catheter zeltich carries the protectivedc ice. The pressntce is trainsmitted titroitgit the S)aCCeIbetteccn1 tUe tivo catheters.

vcinl or arterv the tip of the cathcter imulst bethoroughlly rinsed.

During, these stuidies, the followxing parame-tecrs x crc alxays ai]d con:tinutiou.sly recordedo)n a Sanhorlln 8-chanmi c Polyvi so recorder:satt ration ( or- C"ardiogr en (lye' concentra-tionl ) fr-omii the otitpuit of the ratioing dcvice;inte(rnal (cleetrocardiograam; 805-mIt light in-te.nsity (to rule ouit possible artifacts due tocontact xvith tlhe chamber walls or stasis of1)lood about the catlheter tip. The formiier w as

never secn, anid tlhei latter was founid onily afterthe catheter xxwas wedge(d) In addition, thefollowving Nxxe're' recorded in m-iost instanices:ext(crnal electrocardiogram; initracardiac pres-suires, (at timess, simultaneously from differ-cut sites); a thermistor siginal recordinig respi-ratory phiases 17; external phoniocardiogram.The data obtained by the fiberoptic hemo-

refection. system wvere conmpared wvith thoseof spectrophotomectric analysis of simiiiltanie-ouislv obtained blood samples. The mleasuire-men ts of fib eroptic satuirationis were madex itlhouit prior kinoxwledge of spectrophotomet-ic resuilts. A total of 38 simultltaneouis read-

Iiit)cyaninie gi(ree'11, Ilviisloi, Wcstcott and DuII-miliig, Iinc., Baltimore, \Iaryland.

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ings and samples were obtained with the low-speed instrument and 48 such comparisonswere made with the high-speed instrument.A second type of analysis concerned the

consistency of multiple readings obtainedwithin the same cardiovascular compartment.A total of 537 readings were obtained withthe low-speed instrument and 235 readingswith the high-speed instrument. The durationof time over which these readings were madevaried between 4 seconds and 3 minutes.Heart rates were determined as an index ofthe patient's "stability" at the time of meas-urement. Fiberoptic readings for these twotypes of analyses were taken as the mean read-ing obtained during the period of sampling.This mean was obtained either by an elec-trical averaging circuit or by fitting a meanline to the phasic tracing by hand. When boththe "electrical mean" and a "hand mean" wereobtained in rapid sequence they seldomdiffered by more than 2 per cent saturation,and never by more than 232 per cent. A thirdtype of analysis concerned phasic changes insaturation throughout the cardiac cycle.

ResultsCorrelationThe simultaneous readings taken with the

fiberoptic hemoreflection instruments showclose correlation with the samples analyzed

A

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by the conventional spectrophotometric meth-od. For the high-speed instrument a correla-tion coefficient of 0.966 was obtained for the48 comparisons (fig. 3A). The regressionequation reflecting this correlation (deter-mined by the least-squares method)18 is asfollows:

Y = 0.952x + 2.60Where y represents the fiberoptic reading andx the spectrophotometric reading. The stand-ard error of estimate about the line is 1.99-per cent saturation.For the lower speed instrument the corre-

lation coefficient for the 38 samples is 0.992,and the best equation as above is

Y = 0.852 x + 10.51The standard error of estimate is 1.13-per centsaturation (fig. 3B).The second type of analysis showed a good

consistency of results obtained in the variousconventional sampling sites. This occurred de-spite moderate changes in heart rate andstatus of the patients. For each samplingsite, the standard deviations at 143 sites (atotal of 719 observations) was 2.05-per centsaturation. If only those chambers receivingblood from one orifice are considered, theaverage of these standard deviations is 0.88-per cent saturation (221 observations in 47sites). On the other hand, if only those sitesreceiving blood from two or more orifices,

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Figure 3Correlation between the oxygen saturation determined by means of the fiberoptic hemoreflec-tion system and simultaneously drawn samples analyzed by spectrophotometry. A. Data ob-tained with the high-speed instrument (response time 0.07 second). B. Data obtained withthe low-speed instrument (response time 1.5 second).


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PULL BACK TRACINGRPA~-SVC_AIENT WITH ASD

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Figure 4Thle left-hldlaKl panel shtows a 25-second contintno-nIs trlacing obtaiinedC as the catheter waswtithl-drawn from the righit pnltnonary artery to the stuperior venla cava. The arrotws indicate thetitunes at wthich the catheter wtas milovedI frtom on-e site to the nCext. The8 oxygen satnration inIstrn-ment lhafd a tinme contstanit of 1.0 second for thlis tracing. IThle r'ighlt-lhand(I panel showtvs the with-rirawal tracing throtgh a patent foiataern oviale which tcas funictionally choc(d. The timcle constanltof thze instrtmlent of th1is tracing w5as 0.07 secondl.

such as the superior vena cava, right atrium,right ventricle in the presence of a ventricu-lar septal defect. and pulmonary artery inthe presence of patent duicttus or Blalock shunt,are conisidered, the average of the standarddeviations wvas 2.62 per cent (498 observa-tioins in 96 sites ).The continutiouis recording of oxygen satura-

tion vith the fiberoptic technic allows thedetermination of oxygein saturation in manysites in rapid succession. This is shown in theleft-hand panel of figure 4. The duration ofthe entire tracinig is 25 seconds. In addition,the immediate indication of oxygen saturationwas frequiently of great valuie in aiding theoperator to manipulate the catheter and es-tablish its locationi. The tripod tip (fig. 2B)permitted on-e to follow a highly saturatedstream of blood to its origin and often to pene-trate a small defect. Further, it was notedfrequently that entry into the left atrium xvasheralded by a change in the oxygen saturation

Circulation, Volume YXXI MSarch 1965

before the operator realized this by the posi-tion of the catheter. Figure 4 on tlle left showsa withdrawal from such a positioni.The rapid response of the"ihigh-speed" in-

strument permits study of the changes ofoxygen saturation sxithin the variouis portionsof the cardliac cycle. Figure 5 shlows the re-cordin-gs obtained with the fast inistrumentfrom a 42-year-old boy vith a patent duictuisarteriosus, proved later at surgery. His cal-eulated puilmonic/!systemic flow ratio was1.3/1. In the main pulmoiary artcry the satu-ration is noted to decrease sharply with theonset of systole, from over 70 per cent to 65per cent by the end of systole. The satura-tion increases during diastole uintil the nextsystolic ejection occurs. In the right ventricle,on the other hand, the saturation is noted tohover around 65 per cent. A similar findingwas found in a patient with a Blalock shunt(extreme left-hand side of figure 14).

In patients with ventricular septal defects

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anld norimial piilimimoary vasetlar resistance, thesaturation wvas also noted to decrease xwith theoinset of systole. Figuire 6 Shoxi()N7s a withdrawaltracing obtained from an1 1-year-old l)oyxho had a ventricu-lar septal defect. His L)ul-monic/systemic flow ratio was 1.2/1. Herethe pulImonary artery satutration is ilote(1 tocdecrease at al)out the time of ventricuilardepolarization. Hovever, withini the maini puil-monoiary artery the sattiration is noted to be-gini to riise xvell )efore the, cind of systole. Asthe flictiuationi in sattiration becomes noremarked diuring withdirawal through the rightventricle, it is noted that the sharp rise insatuiration occuirs earlier xvithini the cardiaccycle, s0 that wheni it is maximal it com-mences as early as 0.09 secondl after the onsetof the QRS complex. lRecordinigs from theright vetricle oftenidid niot show as markeda flictuationi, presumahly because the cathc-ter-senising element dlid not pass as close tothe defect as during the tracing shovxi infigrure 6. Figure 7 shoxvs tracings oltainecl in

a patient vith a ventricuilar septal (lefect an-cdmild pulmon)ic steniosis. The pulmonic/systcemI-ic fi(oxx7 ratio equaled 1.4/1. Again the earlysystolic fall, xitlh a subsequclnt rise in satira-tuoir in systole is notedl in the imaini piullmonaryartery. Ini the riglht ventrickl (fig. 7, lower)similar tracinigs aie nioted xvith the differenicethat the systolic rise ini satuirationl occuri-s ear-lier, thoulhli niot nearly as early as in figure. 6.A 13-mointh-old patif it with a 3-to- 1)111-

mo)nic/ systemic floxx ratio shoxvedl a iImtuchlhigher saturationi ini tlhe riglht ventricIe (fig. 8),thlani seeni in the pi-rvionls patienlts. Duiniigearly diastole, the saturation lhad a teindencyto levcel off at 94 per cenlt. 1However, 0.08seconid after tlhei on.set of the P wave a sliarpdecrease ini sattur-ation-i is inotc d. This fall coni-tinni d uniitil the early part of systole wxhen ashar) rise in satuir-ation xvas secen. The contouirancol absolute saturation of the tracing is dlis-tinctly difFerrent fromn those fotunid in patitntsxx ith only a smnall left-to-r-ight sliiimit.

Figure 9 shoxxws tracinig.s fromii a 12-year-ol(1

PTENT DCUCTUS ARTERIOSUSiry Arlory ECG 444A4ghL

iry Arflrv ECO Right Ventricle 4

Figure 5Tracirns otl)itaeincvdith the high-speed instinonntt itn a )actrt citit ci patent dic tnlsacreriiosits. in the tCiainl pnldtonarlij adtt)y aid t-ight venticle, the phasic ehan',cs scc nint thle pihonarty aotetiy are not SeeCn inl thle 1rihht ventr-icle. 0.3., oXygcin satiiratioti;Int E§CG, itnternal clectrocardiogram; Erx EG, extcri-al clectrcac-lictiotc ;tt 05 mnip305 oitillitn'icr'on light 1itensityl (tlhc zce for this triacing is fai l)belot the hottoot ofthe tr-acing); RA, RV, PA, LV, BA, etc., nlets.s otherwise dcesigncitecl ictetc/)dssntetracings. 1l c oxilgen7 satitr-ation20 sectic is oni tle left, the pr-essre secile for hoth pant4soni the r,ight. Left-hliand trfacing obthinel frofnt vth nalitn ltltloltltrll ar'te lru, right-hallttreacing frouti, ucitlh-in. the righlt it'cle.

(irculaiflon Vl;,mr XVXX, Mfarch 7965

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Upper tracing

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90 r

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Figure 6Continuouis oxygen satuiration recordling obtainedl upon with1drawatil from thte rightpuloionariy artery to the riglit ventricular bod(y itn a patient witli a smnall left-to-rig/itshunt throuigh a ventricular septal clefect. Utpper tr'acing is in1tern7al electrocardiogrtam1,lower tracinig is thze oxyfgent1 satutr-ationI, showing niaxirnal flIctufation high in tlhe body(of thle right ventricle, presuina/)lb itn close proximity to the ventricldar septal cleferct.Dutration of tracing is 15 seconds.

VS L R.,.:R"* PS )patient with a ventricuilar septal defect (pul-mIonic/systemic flowx ratio 2.1/1) and pulmo-

M LV nmary vascular obstructive disease. TracingsSv Ii 40-I PC" obtained from the main pulmonary artery

indicate a small lut significant increase in8 1 1420 50 saturation xvith the onset of ejection. This carly

to25 systolic increase in saturationi was not seen in1: I C121 e I t a the puilmonary artery of aniy patient with nor-mt*q(X7rT7T R T |Tmalpilmonary vascutlar resistance. Only a

small amount of fluctuiation in the satuirationwas notcd (from 82 to 86 per cenlt). How-ever, in the right ventricle, wvhere markedvariations in satuirationi were fouind, some trac-

hK' ings shoved a diastolie as well as a systolic

150 a patient witli a ventriicullat septal clefect, i/cild I1n-25 . onic stenosis, antI left-to-rig/t s/hnt. Lotwer tracing

front the same patient shiowing bot/i left and rig/itvetrtziculair pressure tracings simnultatneon sly wit/i theoxyg,en satturtion in. the riglit ventricular bodyl. The

;IGHT 'NT CULAR 0BODY.Ww earlyl systolic frill in saturatioi in the putlmonary arteryis siniilar to that in figuire 5. Grecter flu1ctuation in

Figure 7 the satturationi t/itl ant ear/icr- riise is seen1 in the rightObtcainehd in the pdlnmonaru arterln of ventricle.

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VW, kw" i-R shunt rise in saturation (middle panel), whereas inRight Ventricle others there wx as no diastolic rise in the right

ventricular satuiration at all (right-hand pan-\ |V\ /cl). The low er satur-ations found in the right

venitricle correspoinl well with the right atrialsatturations.

Figure 10 show s the result obtained whenithe fiberoptic catheter wvas in the right ven-tricle. A conventional catheter was placed bythe retrograde route inito the left ventricle. Aprematuire ventricular contraction xvas delib-

r4 +Xerately stimulated by maniipulation of the lefti tg ventrictular catheter. The pressure witlhin this

ventricle indicates an ineffective contraction.The right ventricuilar saturation rose grad-

Figure 8 ually to levels significantly above those re-tion in thte right ventricle int a )atient corded xxith normal sinuts r-hythm. Of furthereft to right shunt th,rong/ a ventricular interest is the sharp rise in satturation vell he-Thlere is a significant rise (front 5 to 94 fore thb normal sinuiis lcat, xwhich followedlontinanitly dlurinig siystole. The appreci-at systemic.saturation notfoundwith premature ventricular conitraction. Thisat sy.stenic .satzzxratiorz not fotinc7l ;vit 1

Ias in figures 6 and 7) indicates a large diastolic rise in satuiration vas frequent, btitnot consistent following premature beats stim-ulated from-n ithin the left ventricle. The lov-er panel of figuire 10 shoxvs a similar situation

l*II|&ECG I CG 11CGE

PA| WOVIry Art"j Riht Ventricl Right Ventricle LV

RV

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Figure 9

Recordings obtainted front a patiernt eith a ventrictular septal defect, pulmonary tasct-lar obstruction, and left-to-right shunt. The left panel shows thle oxygen satulr'ationfront within the nmain pulmonary artery andl pressures from the pulmnonary artery andleft ventricle. Thle rise in1 saturationt is early in systole. The nidcldlc )anel slhows anoxygen saturation tracing front within the right ventricle, near the defect with adiastolic as well as stystolic rise in saturationt. Thle riglit-hand traciiig was obtainedfrom wcithin the riglit venticle, but more distant from the dcfect airl s1iotus onlly thesystolic rise in saturation. Thie oxygen satturationt tracing may be identifiedI by the60-cycle ripple. The off-set in precssures separates the similar pressure tracings in theright and left ventricles.

Cir ula/icon, Volume XXXI, Mafrch 1965

Oxygen saturoiiwith a large /

septal defect. '

per cent) preeable plateau2lesser shunts (shunt.

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UPVC from RVFigure 10

Righlt teienicIlai oxygen sattir5aitiot itncasutIements inla patient withl a ventrictnlair septal lefect, n/Id in-funudibldar piuinoan ic steao.sis, and left-to-ri-hlt sit ititf-ing. T1ie tipper tiacing shorts ci p)reinatore venItricntlarlleontractioit (PVC), iniclieated b1l thce heavj arrow atthe bIottofli, tit tailt (is stimh1late from i ithiin titcleft ventriclc. 'lhc tipper heavjy arr(owc indicates thclaite diastolic ri.s in sctu1rationi. 1Tle lotnc.t panel showsai prc niaiture cntrietilar conttactionstitulatcdfltltdtttitltiitieth ighve11Ventricle, irtdicatecl bl th(elie et l

aIrrorw at tde bottonm. iThere is'io rise in satniratioit inlate cliastol Thei iis at early stustolie rise ill b)o)t1panl)cs, grlcatci iili th c PVC frot 1/ic rIi-aht c;ntric'lc.

where a conventional catheter had been in-serted inito the] righit veintricle and a prematurecventrictilar contriactionxwas stimiulated by ma-nipulationi of this cathicter. Tlhe right ventricu-lar oxygen satiuration rose very promptly to92!. per cent, and thereafter gradually' declined.In no instance did satiurationi rise siginificantlybefore the subse(uIicnit sinutis beat if the pre-mature ventricular contraction. was produicedfro-m witlini the righit ventricle.The recordings in figures 11 aind 12 xx ee o01-

tained from a 7-year-o(ld patient xvith the (iag-

nosis of tet.1tralogy of Fallot. A left Blalockshunt hiad been successfully created, andhlersystemi ic arterial saturation xxvas 83.6 per cenit.Tlhe saturations obtained in the left ventricleshiow a miid-to-late diastolic fall. and a sxstolicrise to a plataull at 95 p(11- cen1t. InI the righitxventricle a imarked liastolic fall in satuirationwas fotiin(, lavelilf at 67 PTe cent, a satti-rationi conmparable to that fotuindl in the righitatriulm. During systole, a shlarp rise in satlua-tioni xvas foundii . Figure 12 showvs a withdraxvaltracing as tlim fiberoptic cathete vwas pulledfrom tile left pulolnllary artery l)aek throuighlthe righit ventricle to the proximity of thetricuispid valve. In the left pulmonary arterythe systolic fall in saturatition is again seenl.Whienl the catheter tilp entered the mnain puil-mnonary artery, a significant over-all fall insattiration was noted. As the sensing tip ap-proached the region of the venitrictular septaldefect, more flluctuiationi in the saturation wxxaspresent, and finially as the catheter approachedthe tricuspid valve, thei sattiration fell to alevel comparable to that found in the rightatrium. The duirationi of the puill-back from theleft pulmoniary artery to the siuperior veinacava, part of wvhich is show n in figure 12, wasonly 26 seconids.

Figuires 13 andl 14 slovo recordiings obtainiedfroim an 18-year-old girl wvith an atrial septaldefect of the secuinduimi vtariety. The rightve,ntricular sattiration ( fig. 13, top ) demon-stratcd a step-like increase in (liastole dtiringexpiration, am(l often a step-like (lecrease dur-ing in.spirationi ( not illustrated ). There xvasvery little change in satuirationi in systole duir-inig anly pairt of thel respiratory eycle. In theright atriumil ( fig. 13 bottomi ) the oxygen satui-raition lad three distiniet peaks. The majorrise, occurred during venitricuilar systole. Dtir-img ventricular (liastole, there wxas a (eclinexxith a large secondary upwxxard peak. A thirdsmnialler rise in satuirationi was noted at the enidof diastole. This last peak began uniformly0.1 second after the onset of the P wave. Theover-all effect of respirationi oni the shiiuntthrouigh the atrial septal defect, as reflectedin pulmnonary artery satuiration, is seeni in thetol) panel of figrtire 14; generally. satuiration

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RIGHT VENTRICLE

Figure 11

Tracings ol)tained from thle left and right ventricle of a patient with tetralogy ofFallot. Note the diastolic fall itn saturation. iat the left ventricle and a systolic rise insatturation in the right ventricuilar body twi7ch suiggest diastolic right-to-left andsqstolic left-to-righlt shutnts.

TETRAL-OY OF FALLOT tTN BLtLOK PULL BACK TRACING

LPA MPA RV inL. RV high RV body

Figure 12

Withdrawal toinaiig froin thte le-ft pulmonary artery to the body of the righit ventricle near thetricwispitl valve int a patient withi tetralogy of Fallot. T'o be noted are thze systolic dips inisaturation in the left puilmonary artery and thte miore marked fluictuiation in saturation high inthe right ventricle, as well as the general fall in, saturation: betwceen the left pulmonary arteryaind miain- pulmonary artery, right ventricular inifinditltihum, and rig,ht ventricuilar body.l)uration of recortling, 14 seconds.

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FIBEROPTICS FOR INTRACARDIAC OXIMETBY

fell during inspiration, anid rose duiriing cxpira-tion1.With the fiberoptic catheter, it is also pos-

silble to monitor continutously the saturationdurinig an exercise stuidy. The pulmonary ar-tery satuirationi prior to exercise wxas 78.5 percent and fell to 65 per cent within the firstminuite of exercise (fig. 14, top). Thereafterthere was nio further significant fall in satura-tion, despite 5 mirnutes of vigorous exerciseduring which the heart rate increased from136 to 170 beats per minuite. The bottom panelii figuLre 14 shows a fast tracing obtained inthe right atrium during the sixth minute ofexercise. In this tracing, the respiratory vari-ations are more marked than in the pulmonaryartery during this exercise and than in theright atrium at rest. Secondly, virtually allthe shunting occurred duiring expiration, re-

795

90

~-85

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InECG

INSPIRAIO

Figure 13Oxygen saturations obtained front a patient wit/ ant

atrial septal defect, secundurn type. The upper tracingobtained in the righ7t ventricle shows the step-likerise in saturation dturinig expiration. The lower tracingobtaiuned in thze nmid right atrium, shlows a marked risein satturationI dturing ventricuilar systole.Circulation, Volume XXXI, Alar -h 196-5

suliting in peak right atrial saturations vir-tuially identical with left atrial saturations.Durinig inspiration, by contrast, the left-to-right shunt seemed to be minimal, if presentat all. The saturations in the right atrium dur-ing inispiration (60 per cent) closely approxi-mate that in the superior vena cava (6332 percent).

DiscussionAfter their initial introduction in 1962,11, 1

the acceptance of fiberoptic technics for thedirect intracardiac measuLremen-t of oxygensaturation by the principle of reflected lightratios, has been sloxv. This has been due, inpart, to thc lack of anl accurate oximeterwhich could be used in vivo and had a fastdynamic response as well as the capability ofdirect recording of the oxygen saturation."'A still greater problem arose from spuriousreadings cauised when the tip of the cathetercame in close proximity to or in actual contactvith the cardiovascular endothelitum. Thisartifact has been shown to cause sizable andunpredictable errors, both in the average val-ue of oxygen saturation reading and in syn-chronism Nvith the cardiac cycle. In our studieswith anoxic dogs, the "wall artifact" xas foundto resuilt in an increase in the intensity of thereflected light, both 805 m/u and 660 myt, andas much as a 30 per cent change in the meansatuiration reading between the right ventricleand puilmonary artery. These changes vereoften phasie and synchronous with the heartbeat. Increased scanning rate and the alter-ations in the tip design have obviated theseproblems.The excellent correlations shoxvn 1)0th for

the slow response (r=0.992) and for thefast response (r = 0.966) instruments indicate,that over the range of oxygen saturations en-countered in cliniical practice, a linear cor-relation exists betveen oxygen saturation asobtained by spectrophotometry and as deter-mined by the fiberoptic oximeter. It should bepointed out that these correlated data vereobtained from two separate catheters, andthat in some cases, despite efforts to keep thetips closely together, they may indeed havebeen in different streams of blood.

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340GAMBLE F,T AL.

Figure 14

Oxyigeit satut a/ion. iracings frormt a patient wciti ait7 aftrial septal de feet sctUmidnmt. Thlenipper pant / s/hows jmimonary aitery saituration obtainedi with the Commtuenemoenttut ofXcrcise. The eatrly dceclite itn oxygert saturatiot is wmell dcetonstrated, a.s ive/i ais the

ittrease) itt the respir'aiory fluwtuiation int saturttaotton. Note cltiage it paper speed. I'llelowett panel shows tite satnaition oi)tained dniritt the sixtit otittnte of exrcise fr[toothle Hoigltt atrinoty. Dnring inspir-ation, i/eicsatiartiott r'et:aillnei r'iativclh .stab/e (atapp)roxiitately 60 percent anidI r,ose shar-ply itith tue oitset of expiration (the rI-espinr-touii/crthcmistori itas a tite dcliaz of app-oxintatihl1 0.2.5 sc coti.d

The data o1)tained from repeated measure-mentes withlin] a sinigle cardiac chamber indi-cate that thle inistriments have great iniherenitstability an1(d conisistency. Signiificanit differ-enees iM. Oxygen satuirationis as estal)lish ed byvin vitro mnethods"' are greater tlhan the stancd-ard error of estimate within the variouis cardiacchamlers. Furthcr, the rapidity wxith wbhiclthe satuirations macly l)e obtained from nui-mnerotus sites, as shlowvn in figures 4 and 12 maxpermit a signiificant reducltioni in the duratiolof cardiac catlheterizatioin.

1n the presence of shLunts, thle iminediatesaturation measurem-nent wxill give ani index ofthe relative amounts of shunited and noin-shunted l)lood which bathe the sensing tip.The fluictuiation in satuirationi fouind in thenain pulmonary artery in the patient with apatent dtucttis arteriosuts may occur l)ecauscduiring diastole no venouis blood entered the

imaini pullmoinary artery, wlhile satuirated blo0continuied to enter throuiglh the patent diuetts.

In1 patients witlh ventricular septal d(feectsan 1(normlal pulmoniary vascular resistance, theuniform findinig of ani early systolic Jail i1saturation in the mc-ain pulmonary artery is ofinterest. This inidicates that the bloodejcltedIr-om the right ventricle at the end of the pre-ceding systole anid remaining in the maini p1l)-on-iary artery duiring dliastole lhas a higher

satutrationi than the 10loo0( forwarded from theright veintricle in early systole (figs. 6 aind 71).This is furtlher substantiated by the riglht xeni-tricuilar tracinigs in. these patients, in whliclhearly systolic increases in saturation are noted(figs. 6, 7, and 8). Con.sequently, in these pa-tienits the left-to-right shu-nt through the ven-triicular septal defect occurred predominantlyduirin-ig systole. The satuirated, shunted 1)1oodentering the right ventricle mixed xvith an

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ever-decreasing volume and therefore as-

sumed a higher proportion of the blood as

systole progressed. These findings do not,

however, exclude scmO lesser amount of dia-stolic shunting.

Tracings obtained from the right ventricle,which show the greatest fluctuation in satura-tion, are presumably those obtained closest tothe ventricular septal defect. This is supportedby the earlier rise in saturation in these than inthe tracings that have a lesser degree of fluc-tuation in saturation (fig. 6). Thus, it becomesapparent that the position of the sensing ele-ment is important in the timing of changes inoxygen saturation, since a finite period of timemust elapse before the saturated blood can

traverse and mix throughout the cardiac cham-ber. Indeed, the degree and timing of thesefluctuations may be useful to establish thepresence and location of a small ventricularseptal defect.On the other hand, the tracings obtained

from the patient with ventricular septal de-fect and pulmonary vascular obstruction (fig.9) show a small, early systolic rise in satura-tion in the main pulmonary artery. This sug-

gests that the early systolic ejectate containsa higher proportion of shunted blood than theend-systolic blood, which remains in themain pulmonary artery. Following the abovereasoning, this would suggest significant dia-stolic shunting. The middle panel of figure 9supports this by showing a diastolic rise insaturation within the right ventricle. The ma-

jority of tracings obtained from the right ven-

tricle in this patient had a contour somewhatsimilar to the last panel of figure 9. Hereone must assume that the catheter vas not ina position to sense blood shunted during dias-tole, while it did record the systolic rise insaturation. Thus, this patient had significantshunting of blood through the ventricular sep-tal defect during both systole and diastole.The rise in saturation following a premature

ventricular contraction stimulated from theleft ventricle indicates significant late dia-stolic shunting (fig. 10). Presumably this oc-

curred because the premature ventricular con-

traction was ineffective and failed to eject its


content into the aorta.2"' With overdisten-tion of the left ventricle due to prolongedinflow, a higher diastolic gradient of pressurecould be built up across the ventricular septa]defect. On the other hand, following prema-ture ventricular contractions stimulated fromwithin the right ventricle, left ventricularpressures were only slightly reduced, whereasright ventricular pressures were markedlyreduced. Therefore, during the premature ven-tricular contraction itself a large gradient ofpressure existed across the ventricular septaldefect and one would expect rapid left-to-right shunting as is shown in the lower trac-ing of figure 10. Because the left ventricle iscapable of ejecting blood in a normal fashion,there is no tendency to become over distendedduring the following prolonged diastole.Therefore, much less late diastolic left-to-rightshunting would be expected to occur thanwith the conditions present in the upper trac-ing.

Figure 11 indicates how bidirectional shunt-ing through a ventricular septal defect maybe studied. The tracing from the left ventrieu-lar body shows a late diastolic fall in satura-tion and suggests significant diastolic right-to-left shunting into the left ventricle. With theonset of systole, this shunted blood was slowlycleared until the catheter was finally bathedin blood from the left atrium. The right ven-tricular tracing indicates that in tetralogy ofFallot significant left-to-right shunting may oc-cur during systole into the right ventricularbody. Figure 12 from this same patient con-firmed the left-to-right shunting, as the mainpulmonary artery saturation is significantlyabove that found in the region of the tricuspidvalve and, not shown on this illustration, ofthe right atrium. Further, the fluctuation inthe saturation tracing is in keeping with thepresence of a ventricular septal defect.

In atrial septal defect, intracardiac shuntinghas been variously considered to be under theinfluence of respiration,19' 22, 23 right ventricu-lar compliance,'19 23 left atrial contraction,24and the relative sizes of the atrioventricularvalves.24 It was suggested that the left-to-rightshunt occurs predominantly during ventricular

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GAMBLE ET AL.

diastole.2., 23 The tracings shown in figure 13indicate that the predominant left-to-rightshunt occurred during ventricular systole. Thisis presumably because continued pulmonaryvenous flow finds easier egress into the moredistensible right atrium, and possibly the sys-temic venous system, than to remain in theleft atrial cavity. The second hump coincidingwith the phase of rapid ventricular inflow maypossibly reflect the effect of the markedly in-creased right ventricular compliance as com-pared with the left ventricle.25 The third,much smaller increase in atrial saturation maybe ascribed to the left atrial contraction caus-ing some further left-to-right shunting. Dur-ing inspiration, saturations were lowerthan during expiration, reflecting increasedamounts of systemic venous blood enteringthe right atrium.22 The influence of respirationand chest compliance was even more dramati-cally shown during increased respiratory ef-fort, such as that seen during exercise. Thesteady low saturation during the inspiratoryphase reflects a dominant systemic venousflow into the right atrium, whereas duringforced expiration, the systemic venous returnwould appear to be relatively excluded fromthe right atrium.

SummaryIntracardiac blood oxygen saturation was

determined in 31 patients, at cardiac cathe-terization, by means of a fiberoptic in vivohemoreflection system, giving an immediatereport. When compared to in vitro spectro-photometric analysis of samples obtainedthrough a second catheter, a standard error ofestimate of only 1.99-per cent saturation(r=0.966) was found for the higher speedinstrument (response time 0.07 second) and1.13-per cent saturation (r 0.992) for theslower instrument (response time 1.5 sec-onds).The average of the standard deviations of

saturation values in cardiac chambers inwhich no primary mixing occurred, was only0.88-per cent saturation. The continuous re-cording of oxygen saturation while moving the

catheter, permits measurements at multiplesites within a brief period of time (14 to 26seconds through the right side of the heart).Oxygen saturation changes can be continuous-ly monitored under changing conditions, suchas exercise. Finally, the higher speed instru-ment permits investigation of changes inoxygen saturation in patients with congenitalheart disease within portions of the cardiaccycle.

References1. VAN SLYKE, D. D., AND NEILL, J. M.: Deter-

mination of gases in blood and other solutionslby vacuum extraction and manometric meas-urement. J. Biol. Chem. 61: 523, 1924.

2. NATELSON, S.: Routine use of ultramicro meth-ods in the clinical laboratory. Am. J. Clin.Path. 21: 1153, 1951.

3. NAHAs, G. G.: Spectrophotometric determina-tion of hemoglobin and oxyhemoglobin inwhole hemolyzed blood. Science 113: 723,1951.

4. WOOD, E. H.: The oximeter. In Glasser, O.,Ed.: Medical Physics. Ed. 2. Chicago, YearBook Publisher, Inc., 1950.

5. ZIJLSTRA, W. G.: A Manual of Reflection Ox-imetry. Netherlands, Van Corcum & Co.Assen., 1955.

6. POLANYI, M., AND HEHm, R.: A new reflectionoximeter. Rev. Scient. Inst. 31: 401, 1960.

7. CLARK, L. C., JR., WOLF, R., GRANGER, D., ANDTAYLOR, Z.: Continuous recording of bloodoxygen tensions by polarography. J. Appl.Physiol. 6: 189, 1953.

8. SOMMERKAmP, H., AND OEHMIG, H.: Herzkathe-ter mit Kunststoffuiberzogener Platinelektrodezur Furtlaufenden Sauerstoffdruckmessung inStromenden Blut. Klin. Wchnschr. 40: 1112,1962.

9. KREUZER, F., HARRIs, E. D., JR., AND NESSIER,C. G., JR.: A method for continuous recordingof in vivo blood oxygen tension. J. Appl.Physiol. 15: 77, 1960.

10. RooTH, G., CHRISTENSSON, B., GUSTAFSON, A.,LINDER, E., AND VANNITAMBY, M.: Direct in-tracardiac tension measurement with a PtElectrode. Acta med. scandinav. 170: 617,1961.

1 1. POLANYI, M. L., AND HEHIR, R. M.: In ViVooximeter with fast dynamic response. Rev.Scient. Inst. 33: 1050, 1962.

12. ENSON, F., BRiscoE, W. A., POLANYI, M. L.,AIND COURNAND, A.: In vivo studies with anintravascular and intracardiac reflection ox-imeter. J. Appl. Physiol. 17: 552, 1962.

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13. ENSON, Y., JAMESON, A. G., AND COURNAND, A.:Intracardiac oximetry in congenital heart dis-ease. Circulation 29: 499, 1964.

14. HUGENHOLTZ, P. G., GAMBLE, W. J., MONROE,R. G., AND POLANYI, M. L.: The use of fiber-optics in clinical cardiac catheterization. II.In vivo dye-dilution curves. Circulation 31:344, 1965.

15. RUDOLPH, A. M., AND CAYLER, G. G.: Cardiaccatheterization in infants and children. Pediat.Clin. North America, November, 1958, p. 907.

16. WATSON, H.: Intracardiac electrography in theinvestigation of congenital heart disease ininfancy and the neonatal period. Brit. Heart J.24: 144, 1962.

17. MONROE, R. G., HAUCK, A. J., AND GAMBLE,W. J.: A simple device for the continuous re-cording of respiration during cardiac cathe-terization. Am. J. Med. Electronics 3: 281,1964.

18. SNEDECOR, G. W.: Statistical Methods. Ed. 5.

Ames, Iowa, Iowa State College Press, 1956.19. NADAS, A. S.: Pediatric cardiology. Philadelphia,

W. B. Saunders Company, 1963.20. WIGGERS, C.: The muscular reactions of the

mammalian ventricles to artificial surfacestimulus. Am. J. Physiol. 73: 346, 1925.

21. LEVY, J. M., MESEL, E., AND RUDOLPH, A. M.:Unequal right and left ventricular ejectionwith ectopic beats. Am. J. Physiol. 203: 1141,1962.

22. BRECHER, G. A., AND HUBAY, C. A.: Pulmonaryblood flow and venous return during spon-taneous respiration. Circulation Research 3:210, 1955.

23. Dow, J. W., AND DEXTER, L.: Circulatory dynam-ics in atrial septal defect. J. Clin. Invest. 29:809, 1950.

24. HULL, E.: Flow through defects of atrial septum.Am. Heart J. 38: 350, 1949.

25. DEXTER, L.: Atrial septal defect. Brit. Heart J.18: 209, 1956.

How Medicine Became a ScienceThe infiltration of medicine by science had so far been slow, but from the middle

of the nineteenth century the progress became rather geometrical than arithmeticalin rate of advance. Up till 1830 the value of microscopy had been lessened by thedifficulty in overcoming chromatic aberration, but in that year Joseph Jackson Lister,the father of the famous Lord Lister, devised a method of remedying that defect. Fromthat time onwards the scope of microscopic observation rapidly extended and the newscience of histology was born. In 1837 Schleiden and Schwann demonstrated the cellu-lar structure of both plants and animals and round about 1850 the microscope be-came the constant companion of the physiologist and pathologist. The most remarkableresult following from the advance of microscopy was the demonstration of the micro-organisms of disease. Though Bassi in 1835 had found that a fungus was the causeof a disease of silkworms, and Davaine and others had seen the bacillus of anthrax,it was due to the immeasurable genius of Pasteur that, from 1850 onwards, bacteriologybecame an established science, and acquired immunity was shown to be a practicalpossibility.-ZACHARY COPE, KT. Some Famous General Practitioners and other MedicalHistorical Essays. London, Pitman Medical Publishing Co., Ltd., 1961, p. 191.


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MICHAEL POLANYI and ALEXANDER S. NADASWALTER J. GAMBLE, PAUL G. HUGENHOLTZ, R. GRIER MONROE,

OximetryThe Use of Fiberoptics in Clinical Cardiac Catheterization: I. Intracardiac

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 1965 American Heart Association, Inc. All rights reserved.

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