British Heart Journal, I974, 36, i-i8.

Fine structure of the bundle-branches'

Thomas N. James, Libi Sherf, and Ferdinand UrthalerFrom the Cardiovascular Research and Training Center, University ofAlabama School of Medicine,Birmingham, Alabama, U.S.A.

Fine structure of the normal left and right bundle-branches was studied with the electron microscope in onehuman and two canine hearts and correlated with light microscopical observations from Io human and 1Ocanine hearts. There was no significant species difference. Though the left bundle-branch was comprised oftypical Purkinje cells, there were numerous interspersed cells with the appearance of ordinary working myo-cardium. Geometric arrangement of the cells in the proximal portion of the left bundle-branch was in one thinsheet divided by numerous longitudinally oriented collagen partitions, resembling a direct continuation of thehistological geometry of the His bundle. Intercellular junctions within the left bundle-branch were throughintercalated discs which contained many long profiles ofgap junction, in contrast with working myocardium,where gap junctions are much smaller. The right bundle-branch was a thin cylinder rather than a sheet anddid not contain any apparent partitioning pattern. Typical Purkinje cells are comparatively few in the rightbundle-branch and cells with numerous myofibrils (appearing as working myocardium in light micrographs)predominated. Junctions between these cells contained fewer gap junctions than those in the left bundle andvery long profiles were less numerous. Widened Z bands were conspicuous in the right bundle-branch cells ofone dog. Some of the physiological implications of these fine structural features are discussed relative toelectrical properties of the two bundle-branches.

For optimal understanding of any biological activityit is essential to appreciate and correlate structuralappearance with functional behaviour. Electricallyspecialized cells of the heart are a special challengefor such correlation. It would be ideal to know thecomplete fine structure of one cell for which allelectrical properties had been accurately defined,but there are formidable problems which have sofar prevented anyorne satisfactorily attaining thatgoal. As a currently suitable compromise, electronmicroscopical studies have been made of cells takenfrom specific regions of the heart with generalknowledge of the electrophysiological behaviour ofthose regions. Examples include the sinus node(Kawamura, Ig6Ib; James et al., I966; Kawamuraand James, I97i), AV (atrioventricular) node (Kaw-amura, Ig6Ib; James and Sherf, I968; Kawamuraand James, I97I), His bundle (James and Sherf,I97i), and Purkinje cells of false tendon in theventricle (Kawamura, Ig6Ia; Kawamura and James,I97I).Received ii June 1973.

1 This work was supported in part by Program Project Grantand MIRU Contract from the National Heart and LungInstitute, and by the Buchholz Arrhythmia Fund.

This study was done to examine the fine structureof normal cells in the left and right bundle-branchesand to compare their appearance in the human andcanine heart. Goals included an assessment of therelative structural homogeneity or heterogeneity ofindividual cells in the two bundle-branches, thenature of their intercellular junctions, and theirhistological geometry. Since electron microscopydoes not readily permit suitable assessment of largesamples of tissue, for studies of fine structure weconcentrated our attention on two regions whereone could with confidence obtain cells representa-tive of the left and right bundle-branches: theproximal few millimetres of the left bundle-branchjust beneath the membranous septum, and themoderator band of the right ventricle. These obser-vations were supplemented with certain lightmicroscopical examiations.

Subjects and methodsTissue for electron microscopy was obtained from twonormal dog hearts and one normal human heart. Thatfrom the dogs was excised and immediately placed incold phosphate-buffered 6 5 per cent glutaraldehydewithin less than two minutes after the hearts were

2 James, Sherf, and Urthaler

removed during general anaesthesia with sodium pento-barbitone (30 mg/kg intravenously). That from thenormal human heart was excised at necropsy about 3hours after death from a gunshot wound ofthe abdomen.Changes caused by this time interval after death arerecognized and have been the subject of specific pre-vious electron microscopical studies (Hibbs and Black,I963; James et al., I966).The general region of the left bundle-branch is readily

identifiable with gross dissection, and removal of smalltissue samples from the mid-portion just beneath themembranous septum in the left ventricle is feasible,though in our experience the precise definition of theanterior and posterior margins of the left bundle-branchis not possible with gross dissection. To assure that thesample for electron microscopy actually represented theleft bundle-branch, the area from which the sample wasremoved was embedded en bloc and histological sectionswere prepared for light microscopical examination. Inboth canine and human hearts the right bundle-branchoften lies deep within the ventricular septum for muchof its course after it leaves the His bundle, emerging onlyas it courses into the moderator band (Truex and Copen-haver, I947). For this reason, samples of right bundle-branch were obtained from that portion ofthe moderatorband facing the direction of the His bundle, since muchof the remainder of the moderator band is comprised ofordinary working myocardium.

From each sample site approximately 20 small cubesno more than i mm in maximal dimension were fixedwith glutaraldehyde and osmium, embedded in Araldite,sectioned on a Porter-Blum ultratome, and examinedwith a Philips 300 electron microscope. Details of thesemethods have been published (James et al., I966; Jamesand Sherf, I968; James and Sherf, I97I; Kawamura andJames, I971).

For comparison with the electron microscopical find-ings, for orientation into intercellular geometry, and forthe question of comparative cellular homogeneity (or itslack), light microscopical examinations of human andcanine left and right bundle-branches were made inI0 canine and I0 human normal hearts. The tissue wasfixed with I0 per cent neutral formalin, embedded inparaffin, and sectioned at 6 to 8 ,u intervals. Goldnertrichrome stain was used for cell detail, and a simple VanGieson stain was employed to demonstrate the collagenframework of the region, as an indicator of cell arrange-ment (James and Sherf, 1971).

ResultsComparison of human and canine bundle-branch cellsExcept for changes attributable to the fact that thehuman tissue samples for electron microscopy wereobtained three hours after death while those from

FIG. I This light photomicrograph is from the midportion of human left bundle-branch andillustrates direct continuity of a working myocardial cell (dark arrow) with a Purkinje cell(white arrow); (Goldner trichrome stain. x 585). See Fig. 8 and I2 for comparative featuresdemonstrated in electron micrographs.

Fine structure of the bundle-branches 3

the dogs were obtained within a few minutes, therewere no apparent differences between cells of thehuman and canine bundle-branches. Changes pre-viously identified as beginning within several min-utes after death include loss ofintracellular glycogen,clumping of nuclear chromatin, variable dilatationof components of the sarcoplasmic reticulum, andvariable swelling and distortion of the mitochondria(Hibbs and Black, I963; James et al., I966). Somemitochondria appeared to be well preserved in the

human tissue in the present study; however, thisstructural integrity varied not only from cell to cellbut even within individual cells. Features that didnot seem to be significantly altered in the humantissue included the appearance of external cellmembranes (both at intercellular contacts and to-ward the extracellular space), the intracellular dis-tribution of virtually all organelles (includingmitochondria), and the distribution and appearanceof myofibrils.

FIG. 2 In this electron micrograph a cross-section of intercellular junction within the humanleft bundle-branch is shown. The three dark arrows indicate gap junctions (formerly called nexusformations or close junctions). Most of the other areas of darkened membranes in the junctionrepresent desmosomes. ( x 24508.) The area enclosed is magnified in Fig. 3.

4 James, Sherf, and Urthaler

Left bundle-branchCell types Although the principal cell seen wasone usually considered a Purkinje cell, there werenumerous cells indistinguishable from ordinaryventricular working myocardium. This was apparentboth at the light microscopical and ultrastructurallevel. Two areas where cells with the appearanceof working myocardium become increasingly pre-valent, as would be expected, are at any point wherethe left bundle-branch penetrates the septum and

where the left bundle-branch is a relatively greaterdistance from the His bundle. Though there is agradual increase in intracellular content of myo-fibrils with increasing distance from the His bundle,in many locations a Purkinje cell joined directly to aworking myocardial cell (Fig. I). In addition toPurkinje cells and working myocardial cells, therewas a third group of cells intermediate betweenthese two types and exhibiting various featurescharacteristic of either; these may be considered

FIG. 3 This excerpt from Fig. 2 illustrates the prevalence of gap junctions (white arrows)present within a cross-section of intercalated disc between two hunan left bundle-branch cells.The gap junctions vary in length. The narrow black arrows indicate desmosomes. ( x 67430.)

Fine structure of the bundle-branches 5

transitional cells (James et al., I966; James andSherf, I968, I97I).In this study the following definition of a Purkinje

cell is applied. It is both shorter and broader than aworking cell, measuring 20 to 40 ,u in width and20 to 6o i in its long axis. Larger Purkinje cells arefound in artiodactyla than in man or in the dog(Kawamura' and James, I97I). Two other dis-tinguishing features of Purkinje cells are the pau-city of their myofibrils and the comparative sim-plicity of their intercalated discs. The scantymyofibrils, which contain only sparse myofilaments,are generally disposed about the periphery of thecell, leaving the perinuclear region rather empty in

appearance (obvious even with light microscopy).As there were only a few wispy myofibrils, there arestill other distinguishing features of Purkinje cells:their intercalated discs contain few fasciae adher-entes, and the external membranes do not have thescalloped appearance typical of working myocar-dium. Infrequency of fasciae adherentes in the inter-calated discs of Purkinje cells fits with the smallnumber and size of myofibrils, since the myofila-ments insert into the disc through the fasciae ad-herentes. Scalloping of the sarcolemma normallyoccurs in registry with the Z band of sarcomeres, thepoint at which transverse tubules enter the cell;consequently, with a sparsity of myofibrils in

FIG. 4 The gently weaving appearance of a typical intercalated disc between Purkinje cellsis seen in this electron micrograph of canine left bundle-branch. Note the exceptionally longgap junction indicated by the three small black arrows. Gap junctions of this length were seenonly in the intercalated discs of Purkinje cells. ( x 30344.)

6 James, Sherf, and Urthaler

Purkinje cells and minimal external scalloping, thereare only rare profiles of transverse tubules to befound.

Other important features of the intercalated discof Purkinje cells include a larger number and size ofgap junctions than are seen in working myocardium,and a simpler or less interdigitated profile on cross-section than occurs in working myocardium (Fig.2-4) (Kawamura and James, 197I). Since the gapjunctions are generally considered to be the sites oflowest intercellular electrical resistance, their multi-plicity and large size fit with the general concept ofmore rapid conduction in Purkinje cells. When theintercalated disc is viewed across the entire Purkinje

cell cut in its long axis, it is seen to weave gentlyfrom one external margin of the cell to the other,often in an oblique direction (Fig. 5). By contrast,the intercalated disc of a working myocardial cellcrosses almost perpendicular to the long axis of thecell, though often making steps from the level of oneZ band to that of more proximal or distal sarco-meres. This difference in appearance of intercalateddiscs is attributable at least in part to the pro-nounced difference in myofibril content of the twotypes of cells, and the appearance of the discs ofworking cells is more in keeping with the maximalintercellular adhesive strength necessary for theirprimary contractile function.

FIG. 5 Here the entire intercalated disc is shown between two Purkinje cells within humanleft bundle-branch. Lateral margins of one Purkinje cell are indicated with the two white arrows,and three points on the intercalated disc are indicated with the black arrows. ( x 6536.)

Fine structure of the bundle-branches 7

Working myocardial cells are characteristicallypacked with longitudinally arrayed myofibrils whichhave numerous mitochondria sandwiched betweenthem (Fig. 6). Myofibrils in Purkinje cells are notonly sparse and contain few myofilaments, but theysometimes course in various directions within the

cell. While some of this appearance, as well as someother features such as the scalloping of sarcolemma,is attributable to the contractile state of the cell atthe time of fixation, the random orientation ofPurkinje myofibrils is too prevalent to be exclusivelyan artefact of preservation or preparation.

FIG. 6 The characteristic orderly array of myofibrils with mitochondria sandwiched betweenthem is illustrated in this electron micrograph of septal working myocardium adjacent to thecanine left bundle-branch. The white letterE is on one erythrocyte within a capillary. ( x I4450.)

8 James, Sherf, and Urthaler

Intercellular junctions Intercalated discs ofworking myocardial cells and Purkinje cells differas discussed above. The only cells in which rela-tively long profiles of gap junction were observedwere Purkinje cells, but not all sections of theirintercalated discs contained these; in some sectionsof Purkinje cells the discs contained no larger anumber or longer profile of gap junctions than areseen in working myocardium. Quantifying the por-tion of intercellular interface which is occupied bygap junction requires three-dimensional reconstruc-tion which was not attempted in this study. Ingeneral terms, a much larger portion of the discs ofPurkinje cells is comprised of gap junctions than istrue for working myocardium, and the only longprofiles of such junctions were seen in Purkinje cells.This was equally true whether the cells were ob-served in cross-section or longitudinal section.

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FIG. 7 Longitudinal partitioning of the proximalhuman left bundle-branch is demonstrated with a van

Gieson stain, in which the red collagen photographsas black. The arrow indicates the general direction ofthe intracardiac course of this left bundle-branch.(x 76.)

Both working myocardium and Purkinje cells havejunctions in a variety of directions, not only end-to-end. However, the number and extent of lateraljunctions and of multicellular junctions were greaterfor Purkinje cells than for working myocardium. Inthe left bundle-branch most Purkinje cells havemultiple lateral as well as end-to-end connexions,sometimes making the long axis of the cell an arbi-trary assessment, particularly since these cells nor-mally tend to be short and broad.

Histological geometry In the region of the leftbundle-branch sampled near the His bundle, thecellular arrangement resembles that of the Hisbundle itself in being longitudinally partitionedby collagen (Fig. 7). This pattern persists for at leastthe first centimetre of the left bundle-branch. Justas in the His bundle, however, the partitioning isnot one of complete separation, periodic crossoversbeing seen between strands. Furthermore, for eachstrand there are rows of two or more Purkinje cellswhich interconnect freely within the strand.Except for there being more working cells as one

approached the more distal distribution of the leftbundle-branch, there was no apparent pattern forthe location or distribution of the working myo-cardial cells seen in the left bundle-branch. Theysimply were interposed at what seem to be randomlocations.

Right bundle-branchCell types Typical Purkinje cells are much lessnumerous in the right bundle-branch than in theleft, and were in fact infrequently observed eitherin light or electron microscopical preparations. Thiswas equally true for human and canine hearts.Working myocardial cells were seen more fre-quently than in the left bundle-branch, though itmay be noted that the sampling site for electronmicroscopical study of the right bundle-branch wasa greater distance from the His bundle than was thesampling site for the left bundle-branch.There was a broader spectrum of cells in the right

bundle-branch having mixed features of workingmyocardium and of Purkinje cells than there was inthe left bundle-branch. For example, relativelyshort cells with more myofibrils than usual forPurkinje cells were abundant (Fig. 8). Furthermore,those cells that contained sparse myofibrils ex-hibited an even wider variety of orientation of myo-fibrillar directions than was seen in most Purkinjecells of the left branch (Fig. 9). Broad bands of Zsubstance were very numerous in the sarcomeres ofright bundle-branch cells in one dog (Fig. io andiI), less numerous in the right bundle-branch of

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the other dog, and were occasionally seen in leftbundle-branch cells of the human heart; they werenot seen in cells sampled from the right bundle-branch of the human heart nor in the left bundle-branch samples of either dog.

Intercellular junctions These were similar tothe ones described for cells ofthe left bundle-branch,except that fewer long profiles of gap junctionwere seen in the cells of the right bundle-branch(Fig. I2-14). Many cells of the right bundle-branch

FIG. 9 The dizzy array of myofibrils coursing in every direction within one cell of the canineright bundle-branch is shown in this electron micrograph. There are also some widened Z bands,seen better in Fig. IO and iI. ( x 9632.)

Fine structure of the bundle-branches ii

contained such a wide array of orientations oftheir myofibrils that the true long axis of the cellwas sometimes impossible to ascertain. Location oftheir intercalated discs was of little help, since theyjoined other cells in a variety of directions, just asdid the Purkinje cells of the left branch.

Histological geometry Based on light micro-scopical appearance, neither the proximal nor distalcomponents of the right bundle-branch contain theorderly separation into longitudinal strands whichis characteristic of the proximal portion of the leftbranch. Instead, the right branch as soon as it

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FIG. IO This cell from canine right bundle-branch illustrates many examples of widened Zbands (appearing as darkened smudges between sarcomeres), random orientation of myofibrils,many 'empty' interfibrillar spaces, and random distribution of mitochondria. Compare this cellto the working myocardial cell shown in Fig. 6. N indicates the nucleus. ( x 7000.)

12 James, Sherf, and Urthaler

leaves the His bundle appears to be a slender to more distal location in the septum. For most ofcylinder of a thin sheet, and within the cylinder the its course within the septum the right bundle-cells connect with each other in virtually all direc- branch is ensheathed by collagen.tions. On cross-section the cylinder is ovoid orround, the shape varying slightly from one heart to Discussionanother and also in any given heart from proximal While structure is no proof of function, it is never-

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FIG. II Many of thefeatures shown in Fig. 10 are seen at higher magnification in this electronmicrograph of canine right bundle-branch. The widenedZ substance, completely random orienta-tion of myofibrils, and the non-relation of mitochondria to myofibrils is apparent. ( x I4450.)

Fine structure of the bundle-branches 13

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FIG. I2 An intercalated disc between two cells in the canine right bundle-branch is indicatedby the three curved arrows, each of which is pointed to a gap junction. The disc shown here isidentical to the ones seen in most of the working myocardium. It may be compared to the discsshown in Fig. 13 and 14 (also from the right bundle-branch) which are characteristic of mostjunctions between Purkinje cells. The cell on the left has more myofibrils than the one on theright, the latter resembling a Purkinje cell. This is a magnified view of one portion of Fig. 8.( X 14450.)

14 James, Sherf, and Urthaler

FIG. I3 A portion of the gently weaving intercalated disc typical of Purkinje cells is shownhere from canine right bundle-branch. Short segments of gap junction are indicated with thefour black arrows. Longer gap junctions were seen more often in the left bundle-branch than inthe right. ( x 2I670.)

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FIG. I4 Desmosomes ofvarying lengthgive this intercalated disc a beaded appearance. Randomorientation of the sparse myofibrils, non-relation of the mitochondria to myofibrils, and paucity ofgap junctions (compared to left bundle-branch) characterize these Purkinje cells from canineright bundle-branch. ( x I4450.)

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x6 James, Sherf, and Urthaler

theless a useful guide. Based on this study of thefine structure of the bundle-branches, there areseveral functional implications to consider. Thesethoughts on function will be discussed under fourheadings: (i) heterogeneity of cell types in the leftbundle-branch; (2) several peculiarities of cells inthe right bundle-branch; (3) nature of intercellularjunctions of both bundle-branches; and (4) histo-logical geometry of the two bundle-branches.

Heterogeneity of cell types in left bundle-branchMethods in current use to measure conduction vel-ocity in myocardium require certain assumptionssuch as homogeneity of cell types, uniformity ofintercellular junctions, and a consistent histologicalgeometry within the segment of tissue to be studied.For example, if the cells in the left bundle-branchdiffer significantly in appearance (as shown in thepresent report) and if their functional properties areas different as their appearance, then measurementsof these functional properties may be expected tovary according to the relative prevalence of one orthe other cell type. Until it is possible to determinethe exact functional properties of individual cellsof the myocardium, the pronounced difference inappearance of various cells in the left bundle-branch may best be interpreted as strongly suggest-ing that these cells also differ in their functionalproperties (including conduction velocity). Proof ordisproof of this interpretation will require physio-logical measurements different from those in generaluse today.

Several peculiarities of cells in right bundle-branchAlthough cells of the left bundle-branch do differin their fine structural characteristics, the greatmajority ofthem are of the type generally consideredas Purkinje cells. By contrast, cells of the rightbundle-branch not only differ from each other, butthere are comparatively few typical Purkinje cells anda distinctly smaller percentage than in the left bundle.Furthermore, the myofibrils in many cells of theright bundle-branch present a virtual maze of con-tractile elements coursing in almost every direc-tion. Widened Z bands of the sarcomeres of cellsin the right bundle-branch were conspicuous insome samples; even though this feature was alsopresent in some left bundle-branch cells, its pre-valence was far greater in the samples of the rightbundle-branch. Since it is not possible to makeaccurate interpretation of sarcomere structure withlight microscopy, which would permit a muchlarger sample size, the prevalence of wide Z bandsin our electron micrographs of right bundle-branch

cells may be attributable to a sampling bias of someunrecognized sort.On the other hand, most features of Purkinje cells

are readily identified with light microscopy, and thepaucity of typical Purkinje cells in the right bundle-branch was a feature of all i i human and I2 caninehearts. Whether this 'non-Purkinje' appearance ofright bundle-branch cells may be interpreted in thesame way as the apparent working myocardial cellsof the left bundle-branch is uncertain, but there aretwo reasons to suspect that the predominant cellsin the right bundle-branch have different electro-physiological properties from working myocardium.First, the abundant cells with numerous myofibrilsoriented in virtually all directions were a prevalentelectron microscopical feature of the right bundle-branch but not of the left; these cells probablyappear as working myocardium on light microscopy,though their myofibrillar orientation is indistinct.Second, the conduction velocity of the right bundle-branch in toto is more rapid than one would expectfrom tissue having as many apparent working myo-cardial cells as appears to be present in the rightbundle-branch based on light microscopical studyalone. Thus, the numerous cells in the right bundle-branch which differ from the typical appearance ofPurkinje cells both in their light and electronmicroscopical appearance may nevertheless be cap-able of conducting as rapidly as typical Purkinjecells, or at least more rapidly than working myo-cardium. This simply further illustrates the com-plex cytological features which must be consideredin attempting to explain even one electrophysio-logical property, conduction velocity.What the wide Z bands of many right bundle-

branch cells may signify is puzzling. It has beensuggested that this appearance of Z bands is indica-tive of sarcomerogenesis (Legato, I970). None of thethree hearts studied with electron microscopy washypertrophied, and the right ventricles in par-ticular were not. However, the possibility of focalhypertrophy not discernible on gross examinationcannot be excluded, though if this were the casesome interesting questions about growth of bundle-branches would arise.

Nature of intercellular junctions of bothbundle-branchesSince no effort was made to quantify componentsof the intercellular junctions, results of which wouldin turn have limited significance because of theunavoidably small size of the samples, it is onlypossible to make general quantitative observationsabout the nature of these junctions. Most of theintercalated discs of both left and right bundle-branches were obliquely oriented and gently sweep-

Fine structure of the bundle-branches 17

ing across between adjacent cells. From their cross-sectional appearance, the intercalated discs seen inthe bundle-branch cells may be estimated to haveless total surface area than the complexly inter-digitated discs of working myocardium. At the sametime, the component comprised by gap junctions inobliquely oriented discs, which are characteristic ofPurkinje cells (Kawamura and James, I97I), appearsto be much larger than seen in intercalated discs ofworking myocardium.

In addition to the differences between inter-calated discs seen in working myocardium comparedto Purkinje tissue, there is a third type of myocardialcell which has still another form of intercellularjunction. This is the P cell most prevalent in thesinus node (Kawamura, Ig6Ib; James et al., I966;Kawamura and James, I97I) but also present in theAV node (Kawamura, Ig6Ib; James and Sherf,I968; Kawamura and James, I97I). P cells, whichare thought to be the site of impulse formation,have the simplest of all myocardial intercellularjunctions on electron microscopical examination,containing almost exclusively undifferentiated re-gions with sparse desmosomes, small and infrequentfasciae adherentes, and only rare small gap junctions.No P cells were found in the present study of thebundle-branches. Since conduction velocity in thesinus node and AV node has been reported to be theslowest in the heart (Hoffman and Cranefield, I960),one may deduce that the undifferentiated region ofintercalated discs is an area of slow electrical spread.In experimental studies causing dehiscence ofdesmosomes, fasciae adherentes, and undifferen-tiated regions but having no effect on gap junctions,there is no significant alteration of conductionvelocity (Dreifuss, Girardier and Forssmann, I966;Kawamura and Konishi, I967; Kawamura and James,I97I). This further supports the interpretation thatrapid conduction in the right and left bundle-branches is attributable to the prevalence of gapjunctions in those cells.

Histological geometry of the two bundle-branchesIn this study the histological geometry of the left-bundle-branch was examined only for the first fewmillimetres beyond its origin from the His bundle.In that region the distinct longitudinal partitioningof the His bundle simply continued directly into theproximal portion of the left bundle-branch. How-ever, as the left branch coursed away from the Hisbundle, its partitioned sheet began to fan out, in-stead of the strands coursing parallel as in the Hisbundle. This thin and broad fan in the proximalsegment of left bundle-branch was separated fromthe underlying septal myocardium by a sheet of

collagen, and the abundance of this collagen makessectioning of left bundle-branch samples for ultra-structural studies more difficult than for tissue withless associated collagen. Neither in the His bundlenor in the proximal left bundle-branch do the col-lagen septa completely isolate adjacent cords ofmyocardial cells, since crossover connexions arepresent. Based on this fine structural appearance,one would expect predominantly partitioned con-duction (or longitudinal dissociation) within thefirst portion of the left bundle-branch as well as inthe His bundle itself. Several recent clinical andexperimental studies support this possibility (Sherfand James, I969, I972; Anderson et al., 1970;Myerburg, Nilsson and Gelband, 1972).

Organization of the proximal right bundle-branchis quite different. It also is sheathed from adjacentseptal myocardium near the His bundle, but oncross-section the right bundle-branch at that pointis round or ovoid instead of being a sheet like theleft bundle. Furthermore, the partitioning by col-lagen so striking in the His bundle and proximalleft bundle-branch is not seen in the right bundle-branch. Instead, on light microscopical examinationthe right bundle-branch cells do not appear to beorganized into longitudinally oriented cords but tointerweave rather loosely and with no clear patternexcept as one multicellular tube. One may thussuspect that the left bundle-branch carries dis-cretely partitioned signals - at least in its proximalportion - whereas the right bundle-branch actsmore as a single unpartitioned electrical conduit.However, what the exact functional significance maybe relative to the electrophysiological pattern ofactivation of the left and right ventricles, based onthe considerable difference in intrinsic appearanceof their respective bundle-branches, remains to bedetermined.

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Hibbs, R. G., and Black, W. C. (I963). Electron microscopyof post-mortem changes in the rat myocardium. Ana-tomical Record, 147, 26I.

Hoffman, B. F., and Cranefield, P. F. (I960). Electrophysiologyof the Heart. McGraw-Hill, New York.

James, T. N., and Sherf, L. (I968). Ultrastructure of thehuman atrioventricular node. Circulation, 37, I049.

James, T. N., and Sherf, L. (I97I). Fine structure of the Hisbundle. Circulation, 44, 9.

James, T. N., Sherf, L., Fine, G., and Morales, A. R. (1966).Comparative ultrastructure of the sinus node in man anddog. Circulation, 34, I39.

x8 James, Sherf, and Urthaler

Kawamura, K. (Ig6Ia). Electron microscope studies on thecardiac conduction system of the dog. I. The Purkinjefibers.Japanese Circulation Journal, 25, 594.

Kawamura, K. (i96ib). Electron microscope studies on thecardiac conduction system of the dog. II. The sinoatrial andatrioventricular nodes. Japanese Circulation Journal, 2S,973.

Kawamura, K., and James, T. N. (I97I). Comparative ultra-structure of cellular junctions in working myocardium andthe conduction system under normal and pathologic con-ditions.Journal of Molecular and Cellular Cardiology, 3, 3I.

Kawamura, K., and Konishi, T. (I967). Symposium on func-tion and structure of cardiac musde. i. Ultrastructure of thecell junction of heart muscle with special reference to itsfunctional significance in excitation conduction and to theconcept of 'disease of intercalated disc'. Japanese Circula-tionJournal, 31, I533.

Legato, M. J. (I970). Sarcomerogenesis in human myocar-dium. J7ournal of Molecular and Cellular Cardiology, I, 425.

Myerburg, R. J., Nilsson, K., and Gelband, H. (I972). Phys-iology of canine intraventricular conduction and endo-cardial excitation. Circulation Research, 30, 2I7.

Sherf, L., and James, T. N. (I969). A new electrocardio-graphic concept: synchronized sinoventricular conduction.Diseases of the Chest, 55, 127.

Sherf, L., and James, T. N. (1972). The mechanism ofaberration in late atrioventricular junctional beats. Ameri-can Journal of Cardiology, 29, 529.

Truex, R. C., and Copenhaver, W. M. (1947) Histology of themoderator band in man and other mammals with specialreference to the conduction system. American Journal ofAnatomy, So, I73.

Requests for reprints to Dr. Thomas N. James, Cardio-vascular Research and Training Center, University ofAlabama School of Medicine, Birmingham, Alabama35294, U.S.A.