Massive Pulmonary Embolism: *

III. Immediate Electrocardiographic Changes

JORGE 0. JUST-VIERA, M.D., Luis F. GONZALEZ, M.D., GEORGE H. YEAGER, M.D.

From the Department of Slurgery, Uniiversity of Maryland School of Medicine, Baltimore, Alaryland

"The clinical evidence of the acute cor pul-monale resulting from pulmonary embolism de-serves consideration because of the frequency andimportance of the condition and of the commondifficulty in diagnosis. The growing readiness ofsurgeons to undertake the operative procedure forthe removal of the embolus from the pulmonaryartery further emphasizes the importance of estab-lishing the correct diagnosis- . ." S. MIcGinn andP. D. White, 1935.;

The experimental study of massive em-bolism regained prominence after the in-troduction of cardiopulmonary bypass tech-nics resulted in sufficient successful em-bolectomies to nearly equal the totalnumber obtained with the Trendelenbergoperation in this century. The developmentof a reliable standardized technic usinglarge clots which produce varying degreesof embolization has led to growing aware-ness that, in dogs, the severity of signs andsymptoms depends on the size of the em-bolus injected and the degree of obstruc-tion produced in the pulmonary artery andits branches.

This report describes: 1) the immediateelectrocardiographic changes following mas-sive pulmonary embolization, 2) the intra-cardiac serum sodium and potassium levelsassociated with lethality and 3) the altera-tion in cardiac size as demonstrated byangiography.

Material and Methods

Unselected mongrel dogs were embolizedwith large radiopaque (barium-blood mix-ture) and nonradiopaque clots prepared bythe method described previously in de-tail.2' The dose of clot given can be ex-pressed in ml. of clot/Kg. of dog weight.Embolization was performed under Nem-butal anesthesia given in a dose of 30 mg./Kg. or less intravenously. Surgical manipu-lation was minimized and consisted of pe-ripheral venous exposures for insertion ofemboli or catheters. Baseline 12-lead elec-trocardiograms (ECG) were obtained withthe dog lying on its back. During and afterembolization Lead 2 was recorded continu-ously. The final site of lodgement of theclots was confirmed in all animals by roent-genographs or by immediate autopsy. Twodogs were eliminated from this study be-cause a significant amount of clot waspresent in the heart chambers. Figure 1summarizes the survival with this method.Group 1. The electrocardiograms of 10

dogs embolized with lethal doses of radio-paque clots amounting to 1.0 ml./Kg. ormore and the electrocardiograms of 6 dogsdying after doses of 2.0 ml./Kg. or more ofnonradiopaque clots were examined andcorrelated with changes in blood pressure,respiration and pupillary size. These havebeen described in detail previously 3 andconsist of the following: 1) a persistentsevere arterial hypotension develops within5 to 10 seconds after embolization, reaches

201

* Submitted February 17, 1964.Supported by U. S. Public Health Service

Grant HE-07171-02 and the Pangborn FoundationFund.

JUST-VIERA, GONZALEZ AND YEAGER

NON RADIOPAQUE

0.1T 0.5 0610.8 09 J11 1.2ML5 0.5 1.0 1.5 2.02.5

DOSE OF CIOT IN ml/Kg

FIG. 1. Survival observed in dogs embolizedwith radiopaque and nonradiopaque clots. TheLD-50 for radiopaque clots amounts to 0.8 ml./Kg.and for nonradiopaque clots to 1.5 ml./Kg. Differ-ence probably results from greater density of radio-paque clots but similar changes occur after injec-tion of lethal doses of each type of clot.

a non-oscillating value of approximately 10mm. Hg within an average of 185 secondsand becomes imperceptible within an aver-

age of 319 seconds; 2) cessation of respira-tion within 85 seconds; 3) pupillary dilationwithin 132 seconds. Arterial desaturationbelow 70 per cent, CO2 retention andacidosis occur within 1 to 3 minutes afterlethal embolization. Survivors compensaterapidly. The blood pressure rises towardsnormotensive or hypertensive levels within60 to 90 seconds after embolization.

Six survivors were also studied: 3 were

embolized with radiopaque clots and 3with nonradiopaque emboli. The electro-cardiographic changes observed in these 22dogs form the basis of this report.Group II. Six dogs received a lethal dose

of radiopaque clot after 7F Cournand car-

diac catheters were positioned into theright and left ventricles. Serum sodium andpotassium levels were determined by rou-

tine flame photometry of heparinized bloodsamples obtained at varying intervals oftime from 5 to 270 seconds after insertionof the embolus.Group III. In 6 embolized dogs serial

Hypaque injections through a No. 12 Bardiccatheter placed in the external jugular veinallowed the study of the immediate gross

alterations in cardiac size or shape or bothand correlation with electrocardiographic

Annals of SurgeryFebruary 1965

changes. The degree of obstruction to bloodflow by the embolus was estimated fromserial radiographs. The 12 dogs in GroupsII and III received 1.0 ml./Kg. of radio-paque clot, a dose which proved lethal in92 per cent of the dogs.

Results

Electrocardiographic changes in heartrate (Fig. 2)

Immediately after embolization, the heart

rate decreased slightly, but quickly re-

turned to the pre-embolic or slightly higherlevel. In succumbing animals, bradycardiadeveloped within 90 seconds and became

I-

a

s

TINE IN SECONDS AFTER INSERTION OF CLOT

280-26240220200

w 80-

160140

4 120

1008060-

PIE-CLOT A o t ie2 lo2 s o .204

CLOT TIME IN SECONDS AFTER INSERTION OF CLOT

FIG. 2. ECG changes in average heart ratesfollowing insertion of radiopaque (Top) and non-

radiopaque (Bottom) clots are remarkably similar;this suggests that addition of barium sulfate doesnot influence the results and permits direct ob-servation of the injected embolus in the animalwith intact thorax. White circles refer to lethalembolization, black to survivors.

202% (SURVivORS) RADIOPAQUE100m90-8070605-04030-20to -

-0

MASSIVE PULMONARY EMBOLISM

marked in 150 seconds. Between 4 to 5minutes after embolization the heart rate

increased momentarily to a rate of 100 to

120 beats per minute and was followed bypersistent bradycardia. In survivors theheart rate remained near baseline levels or

lower after embolization.The onset of bradycardia correlated with

a markedly decreased arterial pressure andbecame severe when cerebral anoxia ap-

peared, as manifested by complete pupil-lary dilation.3 Subsequently the heart rate

increased momentarily, but when the ter-

minal bradycardia ensued the blood pres-

sure was unobtainable and effective pro-

pulsion of blood had disappeared.

Changes in the S-T Segment and T Wave(Fig. 3A, B)

Whereas anesthesia provoked minimalST-T changes, insertion of the clot re-

ST SEGMENT CHANGESST ELEVATED

4e T WAVE__INVERTED

6-I l , ,BASELINE CLOT 5 15 30 45 60 90 240 300 360 420 46 480+

TIME IN SECONDS AFTER INJECTION OF EMBOLUS

FIG. 3A. ECG changes in ST segment and theT wave following the injection of radiopaque clots.Vertical axis refers to number of dogs in whichthe changes occurred; values above horizontal dealwith isoelectric or positive changes, those below,with negative changes. Note initial S-T depressionand the late S-T elevation, with corresponding Twave changes.

ST SEGMENT CHANGESST ELEVATED

6-

Z* MARKED

4-

4- T WAVE CHANGESo T WAVE ELEVATED

Cr6- I I

BASELINE CLOT 5 I5 30 45 60 90 240 300 36 42046TIMIE IN SECONDS AFTER INJECTION OF EMBOLUS

FIG. 3B. ST segment and T wave changes fol-lowing the injection of nonradiopaque clots. Com-pared to Fig. 3A the remarkable similarity in theresults obtained after insertion of both types ofclots can be noted. This appears to be the mostphysiologic experimental technic for the study ofmassive thromboembolism. Such severe changeswere absent in survivors.

suited in S-T segment depression with Twave-inversion within 5 to 45 secondswhich reached maximal severity within 90seconds. At this time the blood pressurewas one-half the baseline level or lower,and cessation of respiration was imminent.The T wave showed a short-lived increasein amplitude or became diphasic during in-jection of the clot.The S-T segment returned to an isoelec-

tric level within 90 to 240 seconds in mostanimals; the T wave became upright, andmany animals had normal sinus rhythm.By this time respirations had ceased, thepupils were dilated and the blood pressurewas 10 mm. Hg or less. Terminally, afternearly 5 minutes following lethal emboliza-tion, the S-T segment became elevated andthe T wave increased noticeably in am-plitude with a sharp, peaked configuration.By contrast, relatively minor changes oc-curred in the S-T segment and the T wavein surviving animal s.

Volume 161Number 2 203

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JUST-VIERA, GONZALEZ AND YEAGER

KH H HHU

IE VIPRE-CLOT 1\ 5 15 30 45 60 90 120 O150 SO 210 240 270 300 360 420

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TIME IN SECONDS AFTER INJECTION OF EMBOLUS

FIG. 4. Onset of severe arrythmias after inser-tion of radiopaque and nonradiopaque clots is de-picted by black bars. Only severe arrhythmias,such as idioventricular rhythm, atrioventriculardissociation and ventricular fibrillation, were con-sidered. Arrythmias occur after cessation of respira-tion. Seven minutes following embolization allanimals presented severe arrythmias.

Alterations in rhythm

Figure 4 depicts the onset of severe ar-

rhythmias observed in dogs reported hereand in unpublished observations. Normalsinus rhythm prevailed immediately afterembolization. Occasional premature ven-

tricular contractions occurred in the firstfew seconds after embolization and bigemi-nal rhythm and first degree heart blockwere noted later. The irritability of thecanine heart, however, is well known.Therefore only the appearance of severe

disturbances of rhythm indicative of un-

equivocal myocardial damage was em-

phasized. Idioventricular rhythm, atrioven-tricular dissociation and, occasionally, ven-

tricular fibrillation usually appeared afterrespirations had ceased.Normal sinus rhythm usually followed ar-

rhythmias associated with embolization. Inanimals embolized with radiopaque clots,sinus rhythm reappeared within an average251 seconds; in animals receiving nonradio-paque clots, sinus rhythm reappeared inan average of 225 seconds. Usually severe

arrhythmias followed this brief attempt to

Annals of SurgeryFebruary 1965

regain normalcy. It is important to beaware of this reappearance of normal sinusrhythm if electrocardiographic changes areused to evaluate therapy for massive lethalpulmonary embolism.

Other changes (Fig. 5, 6)Severe physiologic derangements were re-

flected terminally by measurable increasesin the P-R and Q-T intervals. Prolongationof the Q-T interval was quite marked nearthe final stages. Terminal conduction de-lays occurred. Two patterns appeared re-peatedly near the end: 1) a prolonged Q-Tinterval with a peaked T wave and elevatedS-T segment and 2) intraventricular con-duction delay.

Serum sodium and potassium levels (Fig.7)The serum sodium and potassium levels

determined from right and left ventricularblood showed no significant alterations fol-lowing embolization. Potassium tissue levelswere not measured in these studies and thepossibility remains that intracellular potas-sium may be altered. However ischemiaand anoxemia occur too rapidly in massiveembolization to effect measurable serumpotassium changes, at least under the ex-perimental conditions of this study.

Pulmonary angiography after emboliza-tion

Acute dilatation of the right atrium,ventricle and the cava occurs after massiveembolization and can be observed directlybefore experimental embolectomy. Thepresent angiographic studies confirmed thisdilatation in animals with an intact thorax.The left ventricle filled poorly, and thepassage of contrast material into the aortawas delayed and decreased in quantity.

Discussion

Acute massive pulmonary embolism sig-nificantly alters normal cardiophysiology.

MASSIVE PULMONARY EMBOLISM

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FIG. 5. This dog sur-vived 1.1 ml./Kg. of ra-diopaque clot. Note ini-tial rapid decrease inarterial blood pressure.Early depression of theS-T segment did not pro-ress to S-T elevation,since return to normoten-sive blood pressure levelsprobably relieved myo-cardial ischemia.

The threatening embolus interferes seri-ously with the physiologic dynamics ofblood circulation; by preventing free pas-

sage of blood from the right to the leftside of the heart, the embolus decreasescardiac output, causes hypotension andprovokes an adverse metabolic state be-cause of inadequate perfusion of periph-eral tissues. The most important change is

a rapid sustained decrease in arterial pres-

sure. Shock precedes death from massivethrombo-embolism. The resulting suddenrise in pressure in the pulmonary arteryproximal to the embolus and the ensuingcardiac dilatation greatly increase the workload of the right ventricle. Myocardialischemia results from a combination of 1)reduced coronary blood flow resulting from

so M. 3BP

the initially decreased and terminally re-

versed pressure gradient between the aortaand the right auricle, 2) increased myo-cardial oxygen consumption due to in-creased cardiac work and 3) possible im-pingement upon the vessels within the myo-cardium by increased pressure and stretch-ing.

If the heart overcomes the pulmonaryblock, increased cardiac output restoresblood pressure to baseline values or higherand sufficient blood perfuses the myocar-

dium. The animal survives the life-threaten-ing episode.

The electrocardiographic changes noticedduring the immediate postembolic periodcould result from 1) acute ionic changes,especially potassium and sodium, caused

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JUST-VIERA, GONZALEZ AND YEAGER Annals of SurgeryFebruary 1965

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of 0.7 ml./Kg. this dogdeveloped persistent ar-

terial hypotension. Notereturn to sinus rhythm at195 sec. which could

til l be misinterpreted as im-211" 4 provement when therapy;11J is evaluated if arterial

blood pressure is not ob-tained. Note S-T eleva-tion which accompaniesdeath, along with peakedT wave and prolonged

m.- Q-T interval.

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by myocardial ischemia, 2) myocardial oxy-

gen deficiency originating in the dispropor-tion between oxygen supply and oxygen

consumption and 3) stretching of the myo-

cardial fibers by direct pressure.

Prinzmetal et al.5 studied the nature ofmyocardial ischemia and its correlationwith electrocardiographic changes. Twotypes of ischemia were seen: a severe formcharacterized by S-T elevation, large Rwaves, and small or absent S waves and a

mild form in which S-T depression oc-

curred, often with a decrease in the heightof the R waves and an increase in thedepth of the S waves. Thus severe andmild types of ischemia seemed to producepractically opposite electrocardiographic

changes. If ischemia increased S-T eleva-tions appeared where S-T depressions hadbeen present previously.

Apparently in severe injury the cell mem-brane loses its ability to maintain a normalionic gradient, intracellular potassium de-creases and sodium increases, hypopolariza-tion occurs, and this results in elevation ofthe S-T segment. In mild ischemia intra-cellular potassium levels probably increaseand hyperpolarization of the cell membranemanifests clinically by S-T depression.

Similarly, immediately after pulmonaryembolism mild ischemia occurs; there isS-T segment depression and T wave inver-sion. As the heart becomes severely is-chemic elevation of the S-T segment fol-

206

Pre clot

BP 100

Post clot

11s S*Cor O_

Volume 161Number 2

MASSIVE PULMONARY EMBOLISM 207

ARTERIAL K+ ARTERIAL No +-5 1804 .160i3 f: 140::: *

-2 -120:- 00

MIXED VENOUS K+ MIXED VENOUS No+5 1804 * .. -160::3 * : * 140.: *

2 -120 *

I100

I! II~j-I J I i II IIlllBASELINE 1 15 30 45 60 75 90 1 120 1 150 180 210 24 270 15 | 30 | 60 | 90 | 120 150 180 210 240 270

5 105 135 BASELINE 15 45 75 105

TIME IN SECONDS AFTER INJECTION OF EMBOLUSFIG. 7. Intracardiac Na and K levels obtained following embolization from right and left

ventricles. Alterations in serum electrolyte values could not be correlated with ECG changesobserved.

lows. Unfortunately no significant altera-tions in serum sodium and potassium levelsof ventricular blood occurred after massiveembolism which could be correlated withthe S-T changes. Whether intracellular elec-trolyte changes occur remains to be de-termined since serum potassium levels maynot reflect intracellular potassium concen-

tration.Although DeTakats et al.1 observed elec-

trocardiographic changes after experimentalpulmonary embolism which resembled a

serious interference with coronary bloodflow, they ascribed more importance toreflex vagal inhibition of the heart. Thesequence of events, closely correlated withperipheral vascular collapse however, sug-gests that arterial hypotension secondary tomechanical block in the pulmonary arteryis the central factor determining lethalityin massive experimental thrombo-embolism.

Recent clinical studies which have beensubstantiated experimentally suggest thatstretching of the myocardial fibers, result-ing from alterations in volume or pressure

loads of the heart, is not important in de-termining the electrocardiographic changesassociated with hemodynamic overload ex-

cept when it produces myocardial ischemia-probably because of a disproportion inthe availability of oxygen and its consump-

tion by the myocardium. Diastolic overloadincreased oxygen consumption of isolateddog hearts; this occurs in pulmonary em-

bolism since both the right ventricularsystolic and diastolic pressures rise con-

siderably.2 In addition, right atrial pressure

increases and aortic diastolic pressure de-creases markedly; oxygen availability is cur-

tailed because of decreased coronary bloodflow resulting from the altered pressure

w

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208 JUST-VIERA, GONZALEZ AND YEAGER Annals of Surgery

gradient between the aorta and the rightatrium.The electrocardiographic patterns ob-

served during this study suggest that in-itially the myocardial ischemia producedby the embolus is relatively mild andcauses S-T depression and T-wave inversionand probably results from decreased cor-onary blood flow. The initial ischemia isreversible and the S-T segment can returnto normalcy at this stage if arterial hypo-tension is corrected.

If the pulmonary artery obstruction con-tinues, however, desaturation of the ar-terial blood intensifies the myocardialanoxia. Respirations cease and bradycardiaoccurs. The initial ischemia, originally mildand probably reversible, now becomessevere. The S-T segment returns to decep-tively isoelectric levels and the electrocar-diographic heart rate and rhythm appearto improve briefly. Subsequently the S-Tsegment becomes elevated, a pattern as-sociated with severe ischemia, and brady-cardia reappears. The pupil dilates fully.Peaked T waves, severe arrhythmias, length-ening of the Q-T interval and, occasionally,giant R waves appear preterminally. Deathresults from the failure of the myocardiumto overcome the block imposed by the em-bolus which releases a chain of eventseventually resulting in severe myocardial,cerebral and peripheral anoxia due to acomplete absence of tissue perfusion.

Therapeutic measures must reverse thealtered cardiac physiology and must restorenormal hemodynamics. At present admin-istration of oxygen at increased pressure,partial cardiovascular support and bypass,and immediate embolectomy are beingstudied to determine their efficiency in re-versing changes associated with lethalityfollowing massive pulmonary embolism.

Summary

1. The immediate electrocardiographicchanges observed after experimental mas-

sive pulmonary embolism were studied.These consist of initial severe S-T depres-sion with T wave inversion followed byS-T elevation with upright, peaked Twaves as anoxemia becomes severe. Severearrhythmias appeared after cessation ofrespiration.

2. There was no difference between elec-trocardiographic changes caused by radio-paque barium sulfate clots or by nonra-diopaque clots provided the dose injectedwas lethal.

3. If recovery occurred the blood pres-sure regained its baseline value within 90seconds, and the initial electrocardiographicchanges generally reversed to a normal pat-tern. The reappearance of normal sinusrhythm in dogs without detectable bloodpressure is a possible source of error if theelectrocardiogram is used to evaluate ther-apy in massive embolism.

Acknowledgments

We are grateful to Amin Jurf, B.S., for thepotassium and sodium determinations.

The following aided in the technical aspects ofthis work: Maria P. Alonso-Lej, R.N., George E.Moore, W. Bryan Stauffer and Joaquin Lecaroz-Pomales.

References

1. DeTakats, G., W. C. Beck and G. K. Fenn:Pulmonary Embolism. An Experimental andClinical Study. Surgery, 6:339, 1939.

2. Just-Viera, J. 0. and G. H. Yeager: MassiveLethal Pulmonary Emboli. Surgery, 53:109,1963.

3. Just-Viera, J. 0. and G. H. Yeager: MassivePulmonary Embolism: II. Predictable Mor-tality and Cardiopulmonary Changes in DogsBreathing Room Air. Ann. Surg. (Acceptedfor publication.)

4. McGinn, S. and P. D. White: Acute Cor Pul-monale Resulting From Pulmonary Embolism.J.A.M.A., 104:1473, 1935.

5. Prinzmetal, M., H. Poyoshima, A. Ekmekci, Y.Mizuno and T. Nagaya: Myocardial Ischemia.Nature of Ischemic Electrocardiographic Pat-tems in the Mammalian Ventricles as Deter-mined by Extracellular Electrographic andMetabolic Changes. Amer. J. Cardiol., 8:493,1961.