MI and Atrial Arrhytmia

Myocardial Infarction and Atrial ArrhythmiasBy THOMAS N. JAMES, M.D.

ATRIAL ARRHYTHMIAS occur in about10 per cent of acute myocardial infare-

tions and the commonest of these arrhythmiasis atrial fibrillation.' When atrial fibrillationis sustained after beginning during myocar-dial infarction, it has been reported to beassociated with an 89 per cent mortality.2Although there have been a number of stud-ies on the clinical aspects of the associationof such rhythm disturbances with myocardialinfarction,3-9 little is known regarding theirpathogenesis.

This is a report of findings from 11 selectedcases of patients with myocardial infarctionwho developed atrial arrhythmias. All werenecropsied. Each heart was carefully dis-sected to determine the manner of blood sup-ply to the atria as well as the ventricles, andspecial attention was given to the blood sup-ply to the sinus node and AV (atrioven-tricular) node.10 11 Note was made whetherocclusions in the main coronary artery wereproximal or distal to the origin of the nodalarteries. For histologic study the sinus andAV nodes were cut serially at 2 mm. intervalsin all 11 cases.

Because atrial fibrillation both clinicallyand experimentally is so closely related toother atrial arrhythmias (atrial flutter, atrialtachycardia, etc.), the terms "atrial fibrilla-tion" and "atrial arrhythmias" in generalare used interchangeably.

From the Division of Cardiovascular Diseases,Henry Ford Hospital, Detroit, Michigan.Supported in part by grants from the U. S. Public

Health Service (H-5197) and the Michigan HeartAssociation.

Partially presented at the Scientific Sessions of theAmerican Heart Association, St. Louis, Missouri,Ostober 21, 1960.

Case ReportsCase 1

R.C., a 53-year-old man, died of subacutebacterial endocarditis with rupture of the aorticvalve, and lamellar myoeardial infarction of bothventricles. His final illness was associated withmultiple atrial arrhythmias (fig. 1). At necropsythere was marked compromise of the lumen of theleft circumflex artery by old sclerosis, and thisartery crossed the crux to supply the AV node;in addition there was a recent occlusion of thesmall right coronary artery proximal to the originof the sinus node artery (fig. 2). Ecehymoses werepresent in the epicardium of the sulcus terminalisover the sinus node, and these corresponded toinfarction of the node seen microscopically (figs.3 and 4). No pathology was found in the AV node.Case 2

M.K., a 68-year-old woman, died during anacute anterolateral myocardial infarction withatrial fibrillation. At necropsy most of the leftventricle was infareted and a fresh thrombusoccluded the main left coronary artery; the sinusnode artery arose from the left circumflex branch.There was an old occlusion of the right coronaryartery just beyond the margo acutus and proximalto the AV node, which it supplied. There wasinfarction of the sinus node (fig. 5), but nopathology was found in the AV node.Case 3

J.D.H., a 78-year-old man, died of an acutemyocardial infarction of the left ventricular freewall and septum. His final illness included theonset of atrial fibrillation. At necropsy there wasa recent occlusion of the main left coronary artery,plus an old occlusion of the right coronary arteryproximal to the origins of the arteries supplyingboth the sinus node and AV node. In the sulcusterminalis there were gross epicardial henor-rhages over the sinus node (fig. 6), which corre-sponded to a hemorrhagic infarction seen histo-logically (fig. 7). There was no infarction in theAV node.Case 4

H.L., a 72-year-old man, died of an acute pos-terior myocardial infarction. Initially his electro-cardiogram showed incomplete AV block but later

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Figure 1Electrocardiogram of case 1, showing intermittent simis node activ ity.

he developed atrial fibrillation (fig. 8). At nec-ropsy there were two recent occlusions, one inthe right coronary artery at the Iaar-o acutus andthe other at the origin of the left anterior descend-ing. artery, eomiipIromising the lumen of the mainleft coronary artery also. The sinus node arterya.riose from the left circumflex branch, adjaentto the main left coronary artery, and was partiallyinvolved by the recent occlusion. The right coro-nary arterv crossed the crux of the heart andsupplied the AV node. Histologically, old andnew infaretion involved most of the sinus nodeexit junctions (fig. 9); in the AV node there waslesser damage.Case 5

T.S., a 64-year-old man, died of congestivefailure due to intractable atrial fibrillation withralpid ventricular response. At necropsy therewas old occlusion of the left anterior descending,the left circumflex, and right coronary arteries.The right coronary occlusion was proximal to theorigin of both nodal arteries (fig. 10). Exceptfor some small new foci the ventricular infarctionin most of the left ventricle was old. In the epicar-diuma of the sulcus termninalis there were ecehy-moses over the sinus node (fig. 11), correspondingto infarction present microscopically (figs. 12 and13). No pathology was found in the AV node.

Case 6L.V., al 61-vear-old maan, died of an acute pos-

terolateral myocardial inflrction durinig which hedeveloped atrial fibrillation. At neciopsy therewas ain old occlusion of the riglht coronary artelrvat the miiaro acutus, with that artery suupplying,aln unusually large area of the posterior and lateralleft ventricle, as well as the AY node. There wasalso a, recent occlusion of the smaller main leftcorona my artery proximal to the origin of thesinus node artery, which arose from the evensmaller left circumflex artery. There was infaretionat, the exit junctions of the sinus node, and markedsclerosis of the AY node artery (fig. 14) ; noother pathology was found in the AkV node.

Case 7C.C.B., a 66-vear-old miman, died of posterior

vllocaoIrdiall inifaretion(during. which he developedan atrial tachvcardia of 176 per minute. At mncc-ropsy there was a recent occlusion of the rightcoronari artery proximaal to the ori-in of thesinus node artery, the right coronary continuingto supply the posterior wall and AV mmode. Ecehy-moses were presemmt imm the epicardiuma over thesinus node (fig. 15) and inmfarctiomm was presentin the sinus mnod(e. No pathology-\ was found inl the

\T node.

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-MYOCARDIAL INFARCTION AND ATRIAli ARRIHYTHAIAS

Figure 2Photograph of the heart, e((se 1. -Right arrowindicates the cut edge of a receut occlusion of theright (co'0arYa1( tirteriy; left arrow) in(lic(ltes thesinus node artery, which (trose distal to the occll(-sion. Jo, is the aorta; Ap, the right (trial a))pend-age; SVC, the superior rena a(a; (lcid RV, theright rentricle.

Figure 3A loiu'-p)o ncr photonm icrograph, o'( the sinus node,c(a.se 1. In this tind subsequent photomicrographsN refesrs to the sin as nlode aud A to the rightatriulm. There is hemorrhage and in(ar(tion at the/un('tion of the n1ode a(d atrl Miu .

Case 8

V.HI. t, 62-vealr-old man, (lied at' a lhge antero-lateral llyaocardial infairction, durilng which htedeveloped atrial fibrillation. At necropsy there wasall old occlusion of the right coronary arteryplroximlal to where it crossed the crux, supplyingthe AV node. The left circumflex artery was oc-cluded by an old lesion at the origin of the sinusnode artery, and the left anterior descendingartery was oecluded by a, fresh thronibus 2 eimi.froai its origin. Infaretion was found in both thesinus node anid AV node.

Figure 5Two photomicrographs of the sinas node, ('ase 2,showing (on gestion and hemorrhage (it the junt'-tion of the ncode and (tri((n( w(nder low. po(e('r (tap)and high( power (bottom).

Case 9

V.G., a 64-year.-old mani, died of acute posteriormyocardial infarction. In his final illness he hada variety of atrial arrhythmias, including atrialfibrillation. At necropsy there was a recent oc-clusion of the left circumflex coronary artery near

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Figure 4Higher power photo micrograph of the siuus no(de,case 1, showing hems0orrhage anid degeneration (atthe junction of the node and atrium.

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Figure 7A low-power photomicrograph of the sinus nodeof case 3, showing hemorrhages in the epicardiamand at the junctions of the node and atrium.

Figure 6Photograph of the sinoatrial junction of the heartof case 3. Arrow points to the ecchymoses in thesulcus terminalis directly overlying the sinus node;RA is right atrium.

the niargo obtusus, with the circumflex artery con-tinuing to the crux of the heart and posterior leftventricle, supplying the AV node. There was anold occlusion of the relatively small right coronaryartery proximal to the origin of the sinus nodeartery. Gross ecchymoses were present in theepicardium of the sulcus terininalis over the sinusnode; these corresponded to an infaretion of thesinus node seen microscopically (fig. 16). Nopathology was found in the AV node.Case 10

W.S., a 48-year-old man, had a posterior myo-cardial infaretion 1 year previously and then diedduring a lateral infarction. During both of thesehe had intermittent cessation of sinus node activity(fig. 17). At necropsy there was infarction ofmost of the left ventricle, with old occlusions ofboth the left anterior descending artery and theleft circumflex artery. The latter vessel suppliedthe AV node and the entire left ventricle exceptthe anteroseptal portion, the right coronary arterybeing diminutive. There was a fresh occlusion inthe first centimeter of the left circumflex artery,the sinus node artery arising distal to this, at apoint of old occlusion near the margo obtusus.Infaretion was present in both the sinus nodeand AV node.Case 11

T.L.D., a 66-year-old man, died of myocardialinsufficiency during intractable atrial flutter andfibrillation with a rapid ventricular response; he

also had hemachromatosis. At necropsy there wasold occlusion of the left anterior descending arteryand of the right coronary artery proximal to theorigin of the sinus node artery; the right coronarycontinued to the crux of the heart to supply theposterior wall and AV node. Ventricular infaretionwas streaky and both old and new. There wereedema and hemorrhage at the exit junctions of thesinus node. Degenerative changes were present inthe AV node about iron deposits (fig. 18); despitecareful searching, no iron could be demonstratedin the sinus node.

Comment on the Eleven CasesIn all 11 cases a coronary occlusion was

present proximal to the origins of both thesinus node artery and AV node artery. Insix of the hearts gross eechymoses were foundin the sulcus terminalis directly over the sinusnode. Data relating the nodal histopathologyto the arrhythmias are presented in table 1.

Microscopically, infaretion of the sinusnode was found in all 11 cases. Lesser changeswere apparent in the AV node in five eases.These changes were acute and consisted pri-marily of hemorrhage and edema; however,collagen deposition and fatty infiltrationwere present in scattered foci of all the sinusnodes, suggesting that previous focal damagehad occurred.

The sites of damage in the sinus node werecharacteristic in every case, occurring at thejunctions of the node with the right atriumand sinus intereavarum. Hemorrhages (atthese locations involved Purkinje tracts leav-ing the node and may be presumed to be asso-

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JAMES

Figure 9Low-powver (top) and high-power (bottoni) photo-micrograpvhs of the sinns node, case 4, showingfibrosis, fatty replacenient, and recent hem orrhageait the junction of the sinus node and atrium.

(iated with impairment of normal transmnis-sioni of the sinus impulse to the rest of theheart. Pathologic(changes were less often seenin the central portion of the node or in themore distal atrial muscle, suggesting that theexit junctions of the node may be peculiarlyvulnerable to acute hypoxia.

Ilistopathology of the AV node was lesseonsistent and less striking. Presenee of anoeelusion in the main coronary artery prox-imal to the origin of the AV liode artery inall 11 eases certainly suggests that those AV'nodes must have been rendered hypoxie. Thepossible contribution of this AY nodal hy-poxia to the pathogenesis of atrial arrhyth-mias is discussed later; however, at presentthis remains a speculative probability.

DiscussionAlthough it has long been thought that

atrial arrhythmias ini acute iinyocardial in-farction probably represent concomitant

Figure 10Photograph of the heart of case ), (lemostratingthe sinus node arterql (left arrow.) a risinl fromthe rig7ht coronary artery (right (arrow'7); in thenuclue ~of right coronary artery inlica ted hq the

('crled arrow there iCaS a complete occlusioni. -1 O,the aorta; Ap, the right atrial appendage; SVC,the superior rena cara. The sinus node (1itery'icourses into the sinus node at the junctioi oJ theatrial appendage and rena cora.

Figure 11Another ciew a]f the heart in figure It (case .3),denionistra(tingl the ecchymoses in the su/l(c.s terni-nalis o e thesicnas node, bueing the arera bet eewnthe two )iii he('ads. SiT, the spelr)ior r(en(a (c0 C;and RBA, the right atrium.

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Figure 1J2ALo u'-po Iwer ph otom icrograph of the sin us nodefroin case 5. Hemeiorr)-hagic infarction is presentbetween the bodq of the ncode and the atrium.

Figure 13Mlediin m -powieer (top) and high-pu wer (bottom)photomicrographs o!7 the hemnorrhagfic inifar(tioni atthle juncl(tioni of the no(de (ln t (case 5).

Figure 12BLow-power pwhotonticrograph through the tail ofthe node, 10 mm. from figure 12A. Hemorrhageand old fibrosis hare virtuallib replaced the node.

atrial dliinage, evidence to support this clin-ical impression has been meager. A notableexception was the demionstration by Cushinget al.12 that the commonest elinically recog-nizable manifestation of atrial infarction was

Figure 14Photomicrograph of the two branches of the AI-ncode artery, both sclerosed for more thaw 75 percent of their laminai and surrounded 1)1/ mar-phologicalli normal AT'V ode (case 6).

the presence of an atrial arrhythmliia, hut theydid iiot specifically relate these observationsto the pacemaker of the heart. Atrial infarc-tion in experimental animals is not, however,associated with regular production of atrial

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Figure 16Photomicrograph of the sinus node of ease 9.There is hemorrhage ant the junction of the nodeand atrium, with degeneration of the node.

Figure 15Photograph of the heart from case 7, showing theecchymoses in the sulcus terminalis over the siniusnode, indicated between the two arrows. RA, theright atrium; RV, the right ventricle.

a.rrhythmlias,13' 14 and ligation of the primaryblood supply to the sinus node of the dogonly rarely disturbs the sinus rhythnm.15 Itmust be concluded that atrial arrhythmiasoccurring during acute myocardial infarctionhave a more complex pathogenesis.

There are few studies on the pathology ofthe sinus node, exceptions being the recentreports of Lev16' 1 and Hudson.18 Lev ob-served that increasing fibrosis in the sinusnode is a normal consequence of aging, mak-ing evaluation of old focal lesions there diffi-cult. Hudson has noted that various patho-logic changes in the sinus node are by nomeans uncommon.Based on a study of the 11 cases reported

here, and a review of the. published observa-tions on this subject, the following factorsmay be considered as influencing the onset ofatrial fibrillation (or other atrial arrhvth-mias) during acute myoeardia~l infarction:

1. Depressed sinus node "dominance.'"2. Impaired sinus impulse transmission.3. Vagal and vagomimetic reflexes.4. AV node injury.5. Extranodal atrial injury.

6. Atrial distention.7. Hyperealeemia.8. Increased circulating cateeholamines.9. latrogenic factors.

Usually more than one of these factors ispresent in any Riven case, but each is dis-cussed separately.Depressed Sinus Node "Dominance"

Since the cardiac pacemaker is naturally solocated that its regular stimulation of theheart is distributed with maximal efficiency,any condition producing sustained replace-ment of sinus rhythm by some other rhythmmust either destroy or weaken the sinus im-pulse, block this impulse, or be of such strongpotential itself as to supersede this impulse.Experimental application of aconitine to ca-nine atria is an example of the latter, but itis significant that atrial fibrillation so inducedis self limniting. and aconitine must be reap-plied if the arrhythmia is to be sustained;as the extranodal impulse weakens, the un-damaged sinus node resumes dominance.Whether transmission of the sinus impulse

from the node to the atria can be suppressedwithout damage to the sinus node and atriumis problematical. That the impulse can beblocked in its passage from the atria to theventricles without damaging the AV node iswell substantiated both experimentally andclinically, .and the role of such block is dis-('missed later.

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Figure 18High-power photomicrograph from the AV nodeof case 11, demonstrating iron deposits and de-generation of the nodal fibers in this patient withhemachromatosis.

Figure 17Electrocardiogram (case 10) showing intermittentcessation of sinus node activity during an acuteposterior myocardial infarction.

The present observations suggest that ische-mia or injury of the human sinus nodeinfluences the onset of atrial fibrillation inmyoeardial infaretion. That this alone is in-adequate to produce such arrhythmia waslong ago suggested by the persistence of reg-ular rhythm following destruction of theregion of the sinus node,19' 20 and furthersuggested by the persistence of sinus rhythmfollowing ligation of the sinus node arteryof the dog.15 It must nevertheless be presumedthat ischemia or injury of the sinus node, byweakening normal sinus node dominance ofthe heart, is an important factor in this prob-lem, and particularly a factor in prolongationor sustaining of such arrhythmias.Another important factor depressing sinus

node "dominance" is vagotonia. That somevagotonia occurs in most acute myocardialinfaretions can little be doubted. It has evenbeen stated that increased vagal tone is theuniversal mechanism of sudden death in myo-eardial infaretion.21 The effect on the sinusnode of increasing vagal tone (especially the

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right vagus) is well known22' 23 and consistsof increasing bradyeardia to ultimate cessa-tion of all sinus node activity. When this oc-curs in a patient with other factors favoringthe onset of atrial fibrillation, it must be pre-sumed to contribute to the onset of the ar-rhythmia. In addition there are other effectsof vagal stimulation that favor the onset offibrillation, such as increasing the normaldisparity of repolarization speed in atrialfibers.24

Sinus arrest observed during acute myo-cardial infarction may be the result of eithervagotonia or sinus node ischemia or both, andthe clinical differentiation of the two factorsmay be difficult. Atropine counteracts vago-tonia, but its effect on sinus bradyeardia orsinus arrest due to ischemic weakening ofsinus impulse formation is unknown. In man,vagotonia encountered clinically is unlikelyto be unilateral, and bilateral vagotoniashould result not only in sinus bradyeardiabut also prolongation of AV conduction time;in myocardial infarction, however, not only isthere likely to be bilateral vagotonia, but bothsinus and AV nodes may be rendered isehemicat the same time by a coronary occlusionproximal to both their nutrient arteries. Inevery case in this study the main coronaryarteries were occluded proximal to the originof the blood supply of both nodes.

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Table 1Summary of the Arrhythmias and Nodal Pathology in 11 Cases of Myocardial Infarction

Case Sinus node AV node Atrial arrhythmias

1 Infareted No pathology found Multiple atrial arrhythmias2 Infareted No pathology found Atrial fibrillation3 Infareted No pathology found Atrial fibrillation4 Infareted Infarcted Incomplete AV block, then

atrial fibrillation5 Infarcted No pathology found Atrial fibrillation6 Infarcted Sclerotic AV node artery Atrial fibrillation7 Infarcted No pathology found Atrial tachycardia (176/minute)8 Infareted Infarcted Atrial fibrillation9 Infarcted No pathology found Multiple atrial arrhythmias

10 Infarcted Infarcted Intermittent sinus arrest11 Infareted Degeneration Atrial flutter then fibrillation

Impaired Sinus Impulse Transmission

In all 11 of the cases, infarction occurredat the junctions of the sinus node with theright atrium and sinus intercavarum, regionsthrough which the normal sinus impulse mustpass to the heart. Although hemorrhages atthese points were impressive, in none of thehearts were all the junctions damaged, so thatpotential points of exit still existed.

Since potential points of exit still werepresent, and since in experimental animalsvirtually all the connections to the sinus nodecan be severed without the occurrence ofatrial fibrillation,20 it must be concluded thatimpaired sinus impulse transmission, like sup-pressed sinus node "dominance," may be acontributing factor to the onset of atrial fi-brillation during myocardial infarction, butthat it is rarely capable of producing thiseffect by itself.

Other factors that may impair sinus im-pulse transmission during acute myocardialinfarction are atrial distention and cellularanoxia. In the presence of congestive heartfailure atrial pressure rises and the atriumdistends as the ventricle fails to empty; inaddition to the reflex effects of atrial disten-tion,25 the stretching of the atrial fiberslengthens the distance the normal impulsemust travel, as well as probably further in-creasing the normal disparity of atrial fiberrepolarization. Hypoxia of the atrial fibersduring acute myocardial infarction also con-tributes to atrial dilatation, impaired atrial

conduction, and increase in normal disparityof atrial fiber repolarization.Vagal and Vagomimetic Reflexes

The effects of these very important reflexesthat contribute to the onset of atrial fibrilla-tion during acute myocardial infarction arediscussed in detail under the other headings.Both the origin and specific pathways of thesereflexes in acute myocardial infarction arepoorly understood. For possible mechanismsand routes, considering the pathophysiologyof acute myocardial infarction, one may con-sult the comprehensive reviews of cardiovas-cular reflexes.25-29AV Node Injury

The AV node is an efficient alternate car-diac pacemaker. Persistence of an efficientregular cardiac rhythm in experiments inwhich the sinus node is destroyed is mostlikely due to assumption of pacemaking bythe AV node or juxtanodal centers. It seemsmost reasonable, therefore, to believe thatmain coronary artery occlusions that compro-mise the blood supply to both the sinus nodeand AV node are more likely to evoke a dis-organized rhythm than occlusions that com-promise the blood supply of only the sinusnode. This proved to be the case in the presentstudy.

Since the right coronary artery suppliesthe AV node in about 90 per cent of humanhearts, and the sinus node in about 55 percent,10' 11, 30 it is occlusion proximal to the

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MYOCARDIAL INFARCTION AND ATRIAL ARRHYTHMIAS

origin of the sinus node artery in the rightcoronary artery that is most likely to be asso-ciated with atrial fibrillation.

Klainer and Altschule31, 32 observed thatpatients who developed atrial arrhythmiasduring myocardial infarction often had pro-longation of the P-R interval in their electro-cardiograms prior to the onset of the arrhyth-mia, and further that this AV block could bereduced by the administration of atropine.Although this is strong evidence that a vago-mimetic influence on the AV node was presentin their cases, the possibility that the AVblock was due to ischemia or damage to theAV node rather than to vagotonia was notdiscussed, and the histology of the node wasnot reported.

Injury to the AV node may impair AVconduction sufficiently to reduce cardiac out-put and coronary flow. The importance of re-duced coronary flow in the pathogenesis ofarrhythmias during acute myocardial infarc-tion has recently been stressed by Cordayand others.33 3Extranodal Atrial Injury

Cushing et al.'2 emphasized the clinical im-portance of atrial arrhythmias in atrial in-farction. Although damage to the sinus nodeis probably the most important atrial injury,damage to the "working" muscle of the atriamay also contribute to the onset of atrialarrhythmias during acute myocardial infarc-tion. For example, irritable atrial muscle atthe periphery of such injury may establisha competing ectopic pacemaker, eager to takeover if the sinus node should fail. Such apacemaker may remain regular, but wouldmore likely deteriorate to fibrillation, espe-cially under the influence of other factors.

Additionally extranodal atrial injury mayimpair normal sinus impulse transmission, afactor already discussed, and increase furtherthe normal disparity of repolarization speedin atrial fibers.24 A weakened area of atrialmuscle may also contribute to atrial dilatationfrom any other cause.

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might expect an occlusion proximal to its ori-gin to produce a large atrial infarct. Thisdid not prove to be the case in the 11 casesstudied, only four of the 11 having a grosslyrecognizable atrial infarct, and the largest ofthese was less than 1 cm.2 in size; all fourwere in the right atrium. Thus extranodalatrial injury does not seem to be a regularaccompaniment of sinus node infarction, butis an associated factor contributing to the on-set of atrial arrhythmias in less than half ofthe cases.Atrial Distention

Although listed separately as a contributingfactor to atrial arrhythmias during myocar-dial infarction, which it is, atrial distention'sspecific effects and causes have been discussedunder other headings.Hypercalcemia and Increased Circulating Catecho-lamines

Both these factors influence the onset ofatrial fibrillation during acute myocardialinfarction through their effect on repolariza-tion speed and are discussed together, al-though their pathogenesis differs. Theyfurther increase the normal disparity of re-polarization speed in atrial fibers,22-24 thusfavoring both onset and perpetuation of fibril-lation. They may also enhance any potentialectopic pacemaker.Kleitman has shown that in man hyper-

calcemia normally occurs within a very shorttime after assuming the supine positionsFurthermore, this increase in circulating cal-cium was in the ionizable, or biologicallyactive, form. Although it is well known thatprolonged inactivity, as in poliomyelitis, isassociated with increased calcium mobiliza-tion,36 it is unlikely that these observationsare applicable to patients placed at bed restbecause of acute myocardial infarction. Kleit-man 's observations, however, are certainlypertinent and need to be studied further.An increase in circulating catecholamines

during acute myocardial infarction has beenobserved.37 When of sufficient quantity thesewould not only have a chronotropic effect, butmight raise the arterial blood pressure and

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SINUS NODE ARTERY LIGATION

CALCIUM orEPINEPHRINE DISTENTION

or or RT. ATRIUMNOREPINEPH RINE

+VAGAL STIMULATION

ATRIAL FIBRILLATIONFigure 19

A summary of some experimental observations on atrial arrhythmias in myocairdialinfarction.

thereby produce a vagomimetic reflex (Ma-rey's reflex).25 Acute hypertension does some-times occur during acute myocardial infarc-tion.38Iatrogenic Factors

A number of therapeutic measures com-monly employed in patients with acute myo-cardial infarction may contribute to the onsetof atrial arrhythmias. Prominent among theseis quinidine. Because it suppresses all myo-cardial excitability, quinidine may suppressan already weakened sinus node or AV nodestill further and thereby facilitate atrialarrhythmias. Although this possibility is nota strong contraindication to the use of quini-dine otherwise indicated, its effect on thenodal centers should be kept in mind.The effects of digitalis on the sinus node

and AV node depend on the dosage adminis-tered. In therapeutic levels it mildly sup-presses AV conduction, while in toxic dosesit completely blocks it. In therapeutic dosesits effect on the sinus node is not clinicallysignificant, but in toxic doses it sometimesproduces sinus arrest. In addition to nodaleffects, digitalis accelerates repolarization ofatrial myocardium,22' 23 thus increasing thenormal disparity of repolarization speed inatrial fibers and favoring the onset of atrialfibrillation. As with quinidine, digitalis shouldstill be employed when indicated in myocar-dial infarction, but in determining its indica-tion it is well to remember its effects on theconduction centers.

Pressor amines are being employed with

increasing frequency in the therapy of acutemyocardial infarction with hypotension, andhave undoubtedly been responsible for thesaving of many lives. However, they too maycontribute to the onset of atrial arrhythmias.The two ways in which this may occur are bya chronotropic effect on myoeardium (alreadydiscussed) and by overshooting the therapeu-tic mark and producing acute hypertension.A remarkable example of the latter problemwas recently reported by Smith and Logue ;39their emphasis on the vagomimetic reflexesbrought into play by their therapy is mostimportant.

Other therapeutic measures may also playa role in iatrogenic facilitation of the onsetof atrial arrhythmias, but the ones presentedserve to orient thought to these factors.General Comment

In a recent experimental study on the patho-genesis of atrial arrhythmias in myocardialinfarction the validity of most of these clini-cal considerations was confirmed in the labora-tory,40 and a schematic summary is presentedin figure 19. Not one of the factors listedwas capable alone of producing atrial fibrilla-tion except in rare circumstances; addition-ally, any two of the factors also usually failedto induce atrial fibrillation. When the sinusnode was made ischemic, and calcium, cate-cholamines, or atrial distention was added,then vagal stimulation regularly producedatrial fibrillation. It was concluded that thiscomplex combination, employing only factorsthat are known to occur in the course of

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MYOCARDIAL INFARCTION AND ATRIAL ARRHYTHMIAS

POSTERIOR INFARCTQ in Il1 and aVF N

but not in 1, aVL, HV3-6 A.

ATRIALFIBRILLATION

Figure 20A combination of acute posterior myocardial in-farction and atrial fibrillation indicates an occlu-sion of the first 2 cm. of the right coronary artery.

acute myocardial infarction in man, was avalid demonstration of the true complexityof pathogenesis of atrial arrhythmias in myo-cardial infarction.The consistent demonstration of morpho-

logic changes in the sinus node at necropsyof patients dying of acute myocardial infarc-tion with atrial arrhythmias requires specialstudy of the region that is somewhat moredetailed than technics conventionally em-ployed in the routine necropsy. Numerousdescriptions of the anatomy of the sinus nodeare available.4' 46 To determine whether amain coronary occlusion is proximal to theorigin of the sinus node artery only requiresknowledge of the anatomy of the latter vessel.10, 30 which may arise from the proximalportion of either the right or left circumflexcoronary artery.The frequency of serial sectioning in the

region of the sinus node need not be every5 micra. Sections obtained approximately 2mm. apart are satisfactory to assure incorpora-tion of significant focal lesions of the node.For the average node this produces about 10slides, a number that one can convenientlystudy carefully. Hudson has recently reporteda similar experience in "serial " sectioningof the sinus node.'8Using the normal anatomy of the coronary

arteries in conjunction with the behavior of

HIGH LATERAL

INFARCT

(Q inI1.aVL, HV3-6

ATR IALFI1BRI1LLATIO0N /