I

UNIVERSITY OF OKLAHOMA MEDICAL CENTER

PRESERVATION OF MYOCARDIAL FUNCTION DVRIN(-

CROSS-CI1LUMATION IN TERMINAL 1E•NqXIN fI(T~K

Lazar J. Greenfield, James R. McCurdyLerner B. Hinshaw, and Ronald C. Elkins

Technical Report No. 55University of Oklahoa Medical Center T1Mv4IS Contract.

This document has been approved for public releaseand sale; its distribution is unlirnited

Reproduction in whole or in part is permitted forany purpose of the United States Government 0 D C •\

S•!AUG "7 tg72

MEDICAL CENTER FES AND DEVELOPMEN OFFICE .OF THE UNIF'ERSITY OF OKhLAHOA FOUNDATION, INC. B

80U Northeast Thirteenth StreetOklahoma City, Oklahcma 73104

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DOCUMENT CONTROL DATA R & Da, ._.t ,,tt d h. ,, ,,,. .UIv * . •a. " l,'lr • It , , f rll, hInt"€l h t•I O ~l,*pCl d (.''do.t.,J ,rntbvlltllun ill ..' nailill 'l,1', rt .ini n'l *l{sit .

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MIDICAL CENTER RESEARCH AND DEVELOPMENT OFFICE -NC_.SSIF_]ED-L-.

(of 1IE UNfVERSUIY OF OKLAHOMA FOUNDATION, INC. uNcLAssIFIED

PRESERVATION OF MYOCARDIAC FUNCTION DURING CROSS-CIRCULATION IN TERMINALENDOTOXIN SHOCK

4 . ,, I , ,A No , S (7vp,, o rtport onld.iflclo nve dt/lem)

Technical Report' AU T HOýI" I an ',t I ,smov, mIddle It, l•o I, Int tiame)

L. J. Greenfield, J. R. McCurdy, L. B. Hinshaw, R. C. Elkins

6 •F•ONT Dl• A IE 74. TOTAL. NO. Or P'AGEa lb, NO F. R IF S

June 16, 1972 19 208'i C ON TRAC " OR HANT NO. 98. OMIGINO,'tDN*5 REPORT NUMBERI )

N00014-68-A-0496 55

NR 105-5169h. OTHER REPO.R T NO(SI (Any ofher nout•iera thht mey be onsigned

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Cross-circulation between normal isolated hearts and dogs in terminal shock18-21 hours after administration of endotoxin was performed for a period of 3hours. Of 22 dogs injected with endotoxin, only 9 survived long enough to bestudied and 2 died during the study. The results were compared to 4 normalcontr'ol dogs. Isometric cardiac performance measured by intraventricular balloondistention was not impaired in the endotoxin group which showed consistentlybetter length-tension curves and pressure work than control dogs. No alterationin force-velocity curves was noted in either group. Increases in both oxygenuptake and pressure work in the endotoxin group resulted in no change in calculatedmyocardial efficiency, both effects presumably a result of increased circulatirngcat-cholamines. Results fail to show any deleterious effect on a normal heartperfused with blood from a dog in terminal shock and do not substantiate a primaryrole for the reported myocardial depressant factor.

FORM 547 (PAGE 1

3 ul -e07-58 I I Security Classification A-31400

mPSrVATTOYNL ori~ mA1r)IA F'U1.PVI~oN UURfl'Y

I ~CM)SS-CI!VCULr.[J %Ic IN TE'RMINAL END(Irn)Mcf N S11(0%

[,azar J. Greenifield, Jjuiios P. P~cturdv

I tkornrno B3. Ilinshav, ancil Porialc C. '1J-1k

Technicail Rero~rt No. 55University of Oklahare Medical Center 'nIEMIS Contract

June 1.6, 1972

Riesearch sponsored by the, Off ice of Naval ResearchContract N0OO-14-68--A-0496

Project NTR 1.05-516

Reproduction in whnle or in part is pecrmitted forany purpose of the United Sta)tes;Cvrr~i

Th1is docuc~n rt has been anr~roved for public releaseand sale; its dist~ribution is unlirrited

MEDICAL CINTER RESfARUHT AND DLfVET)M1IThT OFFICEor "IIF UNIW.RSITY OF OKI.AJIOMA FOVNDAT TON, Nw..

I The pathcqcgnes~is of cardiovauscular inSLIF-1ieic'nc:.V in shock remii)F; ron-

I tr~~o\erqil al. ud recent attent-Ion Ims1 iXOfl (m':~ f a pnstj.ihl T.o l / re 1,of the heart.. Ihe cruostiori of a ý'h'oc1 to':in iidi . i ti ng Circula tx.'rV iIn

has beenm debated -7incc! die reports of' (J.-incnon ZD, arICI~h Lucmiot~oxithor

was revived by t-he repoxrts of solis and Docvn iinu -,an Lfmradc~ru 14 15

I who (h scribed Acirculating rnyocardiai or nln f.actý or. lcywuvor, rimh-l

from t~his .lahorator-y7 '9 110 and othIicrs6 vo 11M ;h own normln:I myocarli al pe-Lrfir--

mnanc in the early phaso of endatoxiii shock and no? advorscŽ offects on crmrCii aO

work or nretabolism during aross-circulation wit1h oninm1s i~n intermediato sta'ies

of endotoxin shock. Ther-e is igr(-x--,mnt on thC L1I.Lin~ite depression o4- mvoc.ar-

I dial function which has been dexmnrstrated in oxperbrenfal animals following

Iprolonged heimorrhagic:1 or endotoxin18 shock. S:inilar observations hm-ve be-en

reported in patients whio show signs, of left ventricular fai lure in the later

stages of clinical septic shockl 7 . These e.Y.:ý-rinx-nts werc, desi.6nc-d to rieasure.

card iac orxfornkmioe i n A normal. heart porfusce1 wit~h .1odfro-nl a cloq. in the

I~l~ater or terminal !stages of ernJotox3.n Shock ,;ince thie concont-ration of~ the

do-prr~rswnt factor: is bIx,2vcm] to increase withn 1.1irm-ý

Twe.nty-two healthy adult irongrel. dccq-s we-re adinini stered 7ui LD( of

I purifiod F. coli ondotoxin (lDifco, 1Y-,troit) the afternoon of the (lay prior

to study and returned to their cages with tcesio water )hut without

I - further treatnr-nit. The nine anirm1s alive t1~c- following rurni.ncq (18-21 hou~r!s

later) were anestheti zed with -muall aincurts of' rxn)troh-arbita.L (1.0-",q mmo'kcr).

An endotracheal. tube w&-, inserted and cannulac ir-- 'poresi tionod- .in t~he lorta

I ~ ~~and inferior vena cava through thec femoral artor, and vein..Rh r~~a~r

was maintained by circulating blankets and mniintenance fluicis we•re administor.d itintravenously. Four noinwal untreated dcxis wer," s i milarIv preparc&l 1nr) s-;crvr

as control animals.

Thirte'en nornmll dogs weighing 19-28 k< were anosthet i zeNI wilth pinrAnhar-

Sbital (30 rm./kg) and ventilated with a vo.luxv-'v.cVCIx resp.iracor. The rYreal-

vessels in the mrdiastinum were isolated through a mediran sternotonrl and the

Sazygous vein W left subclavian artery ligatEd. Each animal wa r i

(300u/kg), the vagi. were divided .in the neck, and the braehio-c.phalic artery

Swas canmulated for retrograde perfusion of the aorta (Pig. 1). The right

I ventricle was cannulated through the right atrimi and blood was collected to

prine the perfusion circuit. Cross-circulation was conmrmenced after 1.Acrat-ion

of the pulrnary artery, distal aorta, and both superior and inferior vona

cavae. ";ie isolated heart was perfused throughi the brachio-cephalic canni-l and

;, • coronary perfusion pressure was maintained at moam levels of ]20-130 Mn-!g by use

I• of an atraurnatic occlusive roller pump. With evidence of goCd cross-ci ro•lation

without pressure drop in either ihe host: dog or the isolated heart aorta, the

thoracic contents were removed en bloc and suspended on an external frame bx'

the tracheal cannula. The lungs of the .X].uteod propn9mration wore not vcfnti-

I lated and the host dog was allowed to breatho, :--'ontaneously.

The mitral valve of the isolated heart w;v: nxcisd] throuc'h n left atr'iot-

omy and a ftmestrated plug inserte.x with sevwra.l interruptec sut-ures. /' can--

nu.a was inserted in the left atrium during c losýuro and drained to the venous

;:'eservoir along with coronary return frcui the r ight ventricle. Coronary

Sblood flow was measured, wanred and returned bv o)Urp to the hort animn].. Iso-

volumetric left ventricular function was measured hy a latex balloon cannula

inserted throuqh a small incision in the anox of the left ventricle and con-.

nected to two pressure transducers for measurement of er•]-diastolic (0-40 niig

- .' Q,.

scale) and left ventricular pressu-es (0-200 n=Vv scaeo) The first deriva-

I tive of left ventricialar pressure (dp/clt) was r,,cvdrid 'irrnA] trneous usirnn

a r(sistance-CapaciL~lce differentiati.nq n:tw4ri-I. The sinno-aer:ial node wa.I

I cru.-fl.ed and heart rate controlled using a ctce,,,al, 'r at a rate of 170/min.

SI 'PTcji• rat-urc r)f the isolated heart was ny.masure!l hv a venacava] th•,nmister

probe ..uAd maintaincx] at 370 ± 1C.

I Coronary arterial and venous blood P02 , -'•M2, and pH were measured by

an Instnr-ntation Laboratories blood gas analyzer (Model 113) calibrated

' I prior to each determination with known gas mixtures. Oxygen content was

, measured directly in a Lex-O2-con analyzer with periodic confirmation hv the

Van Slyko •anometric technic. Arteriovenous oxygen and CO2 differences were

j used to determine myocardial 02 uptake (WM0 2 ) ind CO2 output based on measured

coronary flow drained from both left and riqht venwtricles while tle left von-

tri.ular balloon was distended with 5 ml of ;ilin(!. Coronaer, erfus.30n Tirs-4 surn, was maintained by pump adjusterit to nxa,-,, values aboxve 120 rvClq throu!h--

out rJ'i(- study which was consistantly higher than the intravent.ricular isom.tr-ic

I' peak pressure.

Calculations of force.-velocity and lenqth-tension curves were hsed on

I the studies of Enright et. a1 5 assuming the ventricle to be a thick-walled

sphere:

2

I = (to2 f X 1. 36 where F = force (g-wt/cm2 ), P = LV ressure (Deak

systolic) or end-diastolic), re = ondocardia] ventricular radius (cmn), ro

I epicirdial radiui (cm) and 1.36 conversion factor. Tnternal ventricular

* I radius (re) was determined from the volume of the intraventricular balloon

using the equation V 4/3 r 3 and the maximal .oltrn. used to determine

~~~~~~~~~~~~~~~~~~~~~. ..... ... :•..... •......... •........ i ...... .• . .• :. ...... .• : ..-•:,. ... I • '..... '... .... ..:< .• ... , ...... ........t.*- - -

maxirmal radius for plotting the length-tension curve as a porc ni- of tUi

maximum length. The external radius ro was• calculated from the xumi of tht./

I '! volumexs of the balloon ard left ventricular nuscle mass assumini the specific

gravity of the muscle mass to be one. Velocity of the contractile elemlentr

(VCE) wa caJ.tulatcd from the equation VC d,; Y 2 r (mid) where P

ventricnlar pressure (nrnlg).I1Assessment of myocardial "efficiency" was maide by the relationshi.

between pressure "work" (systolic pressure-diastolic pressure) and oxyqen

uptake/100gm LV miass measured directly by wet weight of the triremor left ven-

tricle at the termination of each study:

"efficiency" s - PD

I Data were analyzed statistically 1W, Student's t-test and the criterion for

significanoe based on p < 0.05.I, ~RESUTLTS

Survivors of the TD60 of purified erndotoxin showKI blocod diarrhei, rapid

respiration, and were unable to stand. Of 22 dcoqs injected, only 9 survived

- long enouqh to fe connected to the isolated hearrt preparation and 2 ,o.iO~ dur-incl

thu [period of study. Arterial blood gas and ph analysis showed a co"mxen•at:e d

metaholic acidosis with rmean pH of 7.33 ± .03, Pa C02 of 27.3±1.7 armii and

'I PaO2 75.5±2.6 rrmmig (Table I). These values did not ahange during nerfusion

of the isolated heart in animals surviving the study period but there was a

fall in PaO2 and pH in dogs which died during the study. Mean systemic erterial

pressure (KSAP) in the endotoxin group averaggcl 95 mrrIg in contrast to MSAP of

130 rnnlig in the normal donor doqs prior to cross-circulation. After 60 minutes

"I of cross-circulation, PXAP increased to 1.01 mr.}Pq but this imrovernent was notI,

sustained with ASAP falling to 85 mnqg at 120 minutes and 75 mTdl at 180

I rninutcn (Fig. 2).

Control animals showed moiderate hypoxia under pentobarbital anesthesia i

, without ventilatory assistance (Table I). No significant change in b]xo3

gases or pH occurred during the perfusion study and NAP was maintained ex-

cept for one dog where a fall from 103 nrdig to 70 mIg was noted after thr'ee

I hours.

Cardiac performance in response to stepwise distention of the intraven-

•I• tricular balloon shcwed improvement in peak systolic force in control dogs

j after" one hour of pnrfusion which then stabilized for thu rem-ainder of the

study (Table II). Peak systolic isometric force in the endotoxin gqccun 1I showed a gradual but steady irnprovenrwnt over the thiree hour perfusion Peri,-d

increasing from 61.3 ± 9.1 to 81.5 ± 21.2 g-wt/cm2 . Force-velocity curves in

I control dogs showed no significant change and coronary blood flow did not

SJ" change during the study period.

Isometric length-te~nsion curves showed consistently better rvocardial

4 function in the endotoxin group although the differences were not statistically

significant (Fig. 3). There was little deterioration with tiire and at 1.80

minutes, the endotoxin group function curves remained better than control al-

though the nmter of determinations was too low for statistical significance

(Fig. 4). Similar stability of the force-velocity curves was noted in the

I endotoxin group which did not differ from each other or fran control dogs

(Fig. 5). Measured coronary blood flow tended to increase with tijre during

Sthe study period in the hearts perfused with blood fran dogs in endotoxin

I shock but the increese was not statistically significant.

Calculated pressure work decreased slightly in controls while mnvocardial

I

..... ......

SI

1 02 uptake (MVO 2 ) remained unchanged for a slight but insiq ificant ,

Sin calculate<d ryocardial efficiency at then end of the three hour pe.riW] ()F

study (Pig. 6). In the endotoxin group, both pressure work and WO J n-

K creased during the study resulting in no significant change in mvocardial

efficiency.

DISCUSSMcN

I': Assessment of the role of the heart in irreversible shock following a

ig • lethal dose of endotoxin is ocmplicated by peripheral vascular events whichK• decrease venous return and reduce cardiac output 8 , 1 2 . These effects can be

removed by employLig an isolated heart preparation to which venous returnI from a host animal is maintained constant by purp perfusion. Using this

. Ipreparation, we demonstrated in previous studies that the heart shows no

adverse effects in response to direct administration of endotoxin7 . Simi-_

larly, Weil and others 20 found no evidence of myocardial damage after endo-

toxin, Yutner and Cohen1 3 reported no alteration of myocardial contractility

after endotoxin, and Alican ard cn-workersI found] resistance of the nvocardiur.

'< to endotoxin when arterial pressure was mainta.i ned. Even when cardiac output

and nean aortic pressure were decreased by pump adjustment to match the host

dogs' hypotension for three hours7, c-rdiac power resumed control values

after restoration of control flows and aortic pressure. These findings are

3in agreemrent with Siegel and Downing1 6 who reported myocardial damage only

I after prolonged hemorrhagic hypotension. No evidence has been obtained to

support recent observations by Lefer and co-workecrs14, 1 5 in hesor.'hagic and

endotoxin shock that a circulating myocardial depressant factor is releasedit: from the splanchnic bed which impairs cardiac function directly.

Further studies of a normal heart cross-circulatrd with] a cog in later

, ' stages of endotoxin shock (E-9 hours) similarly showed no al.teration of car-

diac performance in response to afterloading10 . The possibility that the

adrenergic response of the host dog masked a depressive effe-ct on the heart

SI was tested by beta-adrenergic blockade which also failed to reveal a deleteri-

ous effect 9 . IHowever we have observed left ventricular failure in anizals in

I endotuxin shock after a rninimum, of 4-6 hours of hypotensionll. Therefore,

. Ithis group of animals in later shock was selected in the present studiy to

"provide exposure of the isolated normal heart to the highest levels of the

I postulated myocardial depressant factor.

Instead of a decrease in cardiac performance, a trend towards improved

I cardiac performance was noted in length-tension curves and pressure work

consistent with the effects of circulating catecholamines from the host dog

"as proposed by Goodyer 6 . However there was no improvermnt in contractility

I demonstrated in the force-velocity curves and no alteration in M/ocardial

efficiency.

SI The possibility of a circulating toxic substance depressing myocardial

g function early in shock is an iqportant therapeutic consideration which would

i.•ply restriction of infusion fluids. However we find no evidence that the

heart cannot respond to a fluid load early in shock. After 4-6 hours, the

'I corbination of prolonged coronary underperfusion, neural dysfunction froma

cerebral hypoxia 2 , interference with cellular metabolism19 and coronary vas-

I cular cbstruction 4 presumably acts to overcmve cac'pensatory mechanisms and

finally results in cardiac failure.I!: I

SUMMARY •

Cross-circulation between normal isolate-d hearts and dogs in termina i

shock 18-21 hours after administration of enrlotoxin was performed for a

period of 3 hours. Of 22 dogs injected with enrdotoxin, only 9 survived

long enough to be studied and 2 died during the study. The results were

cctpared to four normal control dogs. Iscmeitric cardiac performance measurc,9a

I by intravontricula.r ballcon distention was not impaired in t]he endotoxin

group which showed consistently better length-tension curves and pressure

work than control dogs. No alteration in force-velocity curves was noted

in either group. Increases in both oxygen uptake and pressure work in the

endotoxin group resulted in no change in calculated myocardial efficiency,

ii both effects presumably a result of increased circulating catecholamines.

Results fail to show any deleterious effect on a normal heart perfused with

blood from a dog in terminal shock and do riot substantiate a primary role

for the reported ryocardial depressant factor.I.I

I

I

I..,[

1M. Alicn, ]1., Dalton, M.F., and Hardy, J.D. pi.xperfirentunl. n•c' 1to :

I.hock.. CCircu]atory changes with enjThas.iar upnri cardiac runt.:t ion,/ An. , UrLI. 103:702, 1962.

2. Brown, R. S., Mo&hr, P. A., and Shoemaker, W. C. Effoct of corebracI'- hypotension on the neural regulation of the cardiovaqcular systen.

I ~Surg. %~niec. Obstet. 131-436, 1970.

3. Cannon, W. B, Traumatic Shock. (Ch. IV) Nev York, D. Appleton andCo., 1923.

4. Cavanagh, D., Rau, R. S., Sutton, D. M. C., Bhagat, B. D., andI Bacman, F. Pathophysiology of endotoxin shock in the primate.5 I nAm. J. Obstet. Gynec. 108:705, 1970.

5. Enright, L. P., Hannah, H. III, and Reis, R. L. Effects of acuteregional nyocardial ischemia on left ventricular function in doc~s.Circ. Res. 26:307, 1970.

6. Gcxdyer, A. V. N. Left ventricular function and tissue hypoxia in

irreversibly henorrhagic and endotoxin shock. Am. J. Physiol. 212:444, 1967.

7. Hinshaw, L. B., Archer, L. T., ('reenfield, T,. J. , and uenter, C. A.Effects of endotoxin on myocardial heradynamics, performance and

:I metabolism. Am. J. Physiol. 221:504, 1971.

8. Hinshaw, L. B., Gilbert, R. P., Kuida, H., and Visscher, M.D. Pori-pheral resistance changes and blood pooling after endotoxin in evis-I i

cerated dogs. Am. J.Physiol. 195:631, 1958.

9. Hinshaw, L. B., Greenfield, L. J., Archer, L. T., and Guenter, C. A.Effects of endotoxin on myocardial hemodynamics, performance, undmetabolism, during beta adrenergic blockage. Proc. S•c. Exptl. Biol.i f" ~~Med. 137:1217, 1971. '

10. Hinshaw, L. B., Greenfield, L. J., Owen, S. F., Archer, L. T., andcGuenter, C. A. Cardiac response to circulating factors in endotoxinshock. AMi. J. Physiol. (In press).

: 11. Hinshaw, L. B., Crevnfield, L. J., Owen, S. E., Black, M. R., andGuenter, C. A. Pretipitation of cardiac failure in endotoxin shock.ISurg. Onec Obstet. (In press).

I 12. Hinshaw, L. B., Shanbour, L. L., Greenfield, L. J., and Coalson, J. J.Mechanism of decreased venous- return in subhuman primate administeredendotoxin. Arch. Surg. 100:600, 1970.

13. Kutner, F. R. nnd Cohen, J. J. Effect of elndotocin or isolate. catpapillary muscle. J. Surg. Res. 6:83, 1966.

14. Lefer, A. M., Covcill, R., Marshall, F. F., Hall, L. M., arid Brand,E. D. Ciaracterization of a myocardial depressant factor nresentI in hemorrhagic shock. Pavi. J. Physiol. 21?:492, 1967.

15. Lovett, W. L., Wangensteen, S. L., Glenn, T. M., and Lefer, A. M.Presence of a myocardial depressant factor in Datients in circulatoryshock. Surgery 70:223, 1971.

16. <iegcl, H. W. and Duwning, S. E. Reduction of left ventricular con-tractility during acute hemorrhagic shock. Am. JT. Physiol. 218:772,1970.

S17. 3iegel, J. H., Greenspan, M., and Del.uercio, L. R. Abnormal vasculartone, defective oxygen transport, and myocardial failure in nunianseptic shock. Ann. Surq. 165:504, 1967.

S18. Solis, R. T. and Downing, S. E. Effects of E. coli endotoxemia onventricular performance. Am..J. Physiol. 211:307, 1966.

19. Spitzer, J. J. and Spitzer, J. A. Myocardial metabolism in dogsduring hemorrhagic shock. A. J. Physio!. (In press).

20. Weil, M. H., Maclean, L. D., Visscher, M. B., and Spink, W. W.Studies on the circulatory changes in the dog produced by erindotoyinfrom gram-negrtive microorganisrs. J. Clin. Invest. 35:1191, 1956.

4I

I

iIII

t.IJ

i1 TABLE II C0OMAY AMTEFAL AMD VEMUS =MO CAS RD pH: D=FMWTIONS DVW

CIMS-ClICUIATICN WMt DOGS IN TFM. MMIN S¶UML

i (3•'DML (N = 4)

ITIME (MIN. )

0 60 120 180

( Arterial pH 7.43 ±.08 7.41±.06 7.43±.02 7.43±.02

P0 2 55.3-4.4 51.0±4.0 53.0±4.9 52.5±11.5

PC02 28.2-7.5 28.7±7.7 25,5±6.8 28.7±4.2

I C2 18.0±0.5 17.7_+0.8 17.3±0.6 16.8±0.8

r' 31.4±3.9 3.10±3.7 30.4t4.9 32.9±2.6

I Venous pH 7.40+-07 7.39±.05 7.40±.02 7.39±.01

I P0 2 33.3±.2 32.3±3.3 30.3±5.2 32.5±4.5

p 30.3±6.3 32.0±6.1 28.3±4.2 31.5±2.5

I 213.0 4.8 12.4±1.1 11.1±1.8 11.3±0.5

C0O 36.5-2.8 35.8±3.3 36.3±3.6 37.4±2.8

ENIDDYIXIN (N 9)

Arterial pH 7.33:t.02 7.35±.04 7.38±.05 7.28±.06

IP02 75.5 -p2.6 74.5±1.6 74.0±3.3 70.3±5.4

27.3t+.7 27.0±1.7 25.3±0.6 27.0±3.9

I 17.9 tI.2 17.9±1.4 16.8±2.7 20.3±2.2

28.7±1.9 28.5±2.2 28.8i2.3 25.2±0.9

"Venows pH 7.32,.03 7.31-+.03 7 . 33.6. 03 7.26±.05: P02 36.8:t1.7 35.6+2.5 34.5±2.8 37.7±5,5

p C02 32.5 a.0 32.3±1.9 31.0±1.0 34.2±2.0

0211.7tD.9 10. 9±0. 8 9.5±1i.9 12.6±1.9

C0233.4 a.0 34.04-2.3 34.2+2.6 32.5±1.9

U I

*Values -- man -± S.D

i• I p - as tension in nrmig

i ~C q as capacitance in ml.

iii

• I•

I

Li

i

' , I !

K

ITABUE I I

i , PEAK SYSMoLIC IScmTRIc FoRCE (Fs) coATED DURXNr MAXIMraW BALWX

I! DINFTItm IN ISOLATED I-ARTS CMSS-CIrzULATED WITH DRL

OR ENDYIOXiN SHocm DOxG;s

TIME (MIN.)I Fs o/M2) 0 60 120 1o80

I Control (N- 4) 38.7±11.1 57.0+15.2 51.5±10.6 44.6+12.0Endotoxin (N 9) 61.34 9.1 64.1± 9.0 66.7+12.8 81.5+21.2

j;

S ,1.

4

IIII

4'

<WI

IAI

Ilo A< \

POAJo&/~If

Figure 1. Schenatic diagram of the isolated heart preparation peninitting

j I cross-circulation with a dog in endotoxiri shock through the

femral artery and vein. R~etrograde perxfusion of the aorta

is shown with coronary venous return from the right and left

heart returned to a reservoir and then to the host dog. Left

ventricular fun-ction is assessed by stepwise distention~ of the

intraventricular ballo on.*

JC-

;1

MAP (host Dog)I mm Hg

150-- 1/2 s.d.

100- o ................!J 0 ........ .

50 *-. Controlo-...o Endotoxin

I I

0 0' 601 120' 180'

III Figure 2. mean systemic arterial pressure in control and erdotnxin shocked

dogs during the study period. After transient iiprovernmt during

cross-circulation in the endotoxin group, there was a progressive

fall in mean pressure.

LI

Ii

I,

II

- =Fs"g-wt/cm2

1 80.

I "-- Control o120'

0 O..... oEndotoxin ." 060,,:,., ,e60'

... 20140 0..".'0400

20*

I0

p .. " p "

S0eo 70 80 90 100Percent Maximum Balloon RadiusI

SFigure 3. Length.-tension curves showing the relationship between systolic

I forces (Fs) on the ordinate and increasing balloon sLze on the

abscissa repeated at hourly intervals during cross-circulation.

Although the endotoxin group (n = 9) shows higher peak iscoetric

force than control (n = 4) the differences were not statistically

significant.

I.I|

I"I T

Fs 1801g-wt/cm

80 ...- / jI *-e Control/

o-m..-o Endotoxin

•', 7"~~60- 7 09 0

j ~~20 .

70 80 g0 100Percent Maximum Balloon Radius

Figure 4. Length tension curves showing the relationship between peak sys-

tolic force (Fs) and increasing balloon radius after 180 minutes

" Iof perfusion. The mean Fs is consistantly higher in the endotoxin

groUP than in the control dogs although the number of studies is

~ I too wall for statistical s~gnificance.

Ic rn/sec

80-

60-

0-0 0.

4,0

30-

20

;0 20 30 40 so Go 7

g-wt/crn2

Figure 5. Force-velocity curves inscribed in a typical isolated heart

~~ [ preparation perfused with blood frcmi a dog xin terminal endeotoxin

shock. No0 significant change is noted at the sam intraventricum-I Ilar vour (15cc) during the stixly period.

II

- mm Hg1 cc/mnm/gm

10II

r•I I•-•.co I o -. ... .... I •......T

L *---- Control

S......o E nd oto x in

00 60' 120, 1801

I

Figure 6. Calculated ryocardial efficiency based on the ratio between

.1 pressure work and oxygen uptake of the ventricle in control and

endotoxim perfused hearts. No significant differences were noted

between the groups or with time although a proportional increase

f in both pressure work and oxygen uptake was noted in the endotoxin

group.

rI.4I