Download The Morphogenesis of Transposition of the Great Vessels

The Morphogenesis of Transposition of the
Great Vessels
By ROBERT P. GRANT, M.D.
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mechanical effects of the spiraling flow of
blood through the bent primitive cardiac
tube. Transposition could be due, then, to an
abnormality in the spiral course of blood
flow, and this, in turn, perhaps a result of
a disturbanee in the bendinlg of the cardiac
tube. The hemodynamic theory has received
considerable impetus in recent years as a
result of the experiments of Goerttler2 and
the observations of deVries anid Saunders.'
However, while hemodynamic factors may be
the energy source responsible for the anomaly, such a theory does not identify the
growth abnormality that takes place. Furthermore, as we shall see, the architectural
changes in transposition are much more constant and systematic from case to case than
one would expect from the vagaries of blood
flow alone. Goerttler realized this and pointed
out that hemodynamic forces may be only a
participating factor and that other growthgoverning mechanisms must also play a part.
A quite different approach was taken bv
Spitzer in 19234 in developing a phylogenetic
theory of transposition. Following the lead
of Keith, Hochstetter and others, he recapitulated normal heart development in terms of
heart forms to be found earlier in the animal
kingdom, and from such phylogenetic data
developed a system of segmental rotations in
the heart tube, alternate paths of septation,
and changing hemodynamic requirements to
explain normal heart development. WShile his
work can be only briefly described here* he
noted certain resemblances between the heart
with transposition and the reptile heart. In
the reptile (notably the crocodile) three great
vessels arise from the ventricles, two from
the right ventricle (a right aorta and a pulmonarv artery), and one from the left ven-
IN THE COURSE of a study of the embryology of the flow pathways in the human
heart,1 it became apparent that there might be
a simpler way of looking at the morphogenesis
of transposition of the great vessels thani the
current torsion-detorsioni theory. To evaluate
the validity of the new explanation a comparison was made between the architectural
changes found in hearts with proved transposition and the changes to be predicted
from this and other theories of its morphogenesis. While there ha-ve been numerous
descriptive accounts of the heart in transposition, none has approached it in a systemiatic, semi-quantitative way, with use of
objective criteria for case selection. The
results are described in the presenit paper.
While they agree in all regards with the
proposed theory, cardiac development is subtle and many aspects of even normal heart
development are poorly understood. It would
perhaps be wiser to consider the proposed
theory as a "way of looking at transposition"
rather than being itself an adequate explanation of its morphogenesis.
Previous Theories
In effect, transposition is a reversal of the
coiling of the venous and arterial flow paths
responsible for the double circulation. Therefore it is not surprising that notions of the
mechanism of development of transposition
would be derived from theories of how the
normal crossover of the two circulations is
brought about. One of the oldest theories suggests that the normal coilinig in the bulbar
and truneal regions is a response to the
Work done at the Pathologisches Institut of the
Ulniveirsity of Goettiingen, Western Germany (Prof.
J. Linizbach), during the tenure of a Fellowsship
frXom The Commoniwealth Funid.
For more comprehensive review of this and other
theories of transposition see references 5, 6, and 7.
Present address: Office for International Research,
National Institutes of Health, Bethesda 14, Maryland.
Circulation, Volume XXVI, November
1962
819
820)
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triele (a left aorta). He postulated that in
transposition there is a torsion of the bulboventricular septum, abnlormal in man but a
r:ecapitulationi of an earlier animal fornm. As
a result, the left aorta bgecomes obliterated,
the reptilian right aorta regains pateney, and
the puilnmonary artery is brought into alignuiei:t with the left ventriele. In this way
transposition (aand several other anomalies)
were explained by Spitzer in terms of homuoloogies with normal architectural findings in
itiore primitive aniilmal foris. In Spitzer 's
day the idea that congenital anomalies were
instanees of species-reversal (the ''throwvback ') was still popular in the lay miind,
although biologists had discredited it. Today
the ilotioi is in even less repute, and it is
niot thought to play a significant role in
teratology or mutation.8 Furthermore, Spitzer
leaned heavily upon teleology in his explanationis, as if one part of the heart might
somuehow "'know," what the funetional re(Juiremients of another part of the heart might
be at sonme later day or in some later evolutionary state. Finally, while phylogeny provides fascinating glimnpses into the intricate
m1etwork o-f evolutioni (the notion that evolutioIn is a "'chain'' of interlocking links is no
lonoger tenable) it can shed light onlv iiidirectly, if at all, on problemns in teratology.
But Spitzer's notion that there was a series
of inidependeint torsiolnal events at different
parts of the primuitive heart tube stimulated
further w-ork along this line. Rokitansky had
long before suggested that imisplacement of
the two truncal ridges was alone an inade(uilate explanation for the nmorphogeinesis of
transposition and he felt that there imust be
torsion of some other part of the ventricular
septal systenm as well. In 1935 Pernkopf and
Wirtinger9 carefully studied the torsional
events that appear to take place in the heart
durinog niormal developmnent and postulated a
torsional abnormality for transposition. They
(coieluded that torsions of as much as 180
degrees might take place at eacli of three
levels and at different phases of growth ini
the heart tube and developed an exceedingly
GRANT
complex system of torsions and detorsions at
different levels at different times which, they
believed, brought the simple heart tube into
its complex adult form. Such a formulation
offered a ready explanation for transposition
and other syndromes with iniversion or apparent misplacement of cardiac components.
Pernkopf and Wirtinger developed their
data from the study of wax models of humna-ln
fetal hearts at different ages, usinog the various bulbar and truncal ridges as landmarks
for the recognizing of torsions. They believed
there were four truncal and two bulbar ridges
in man. Abnormal torsions could bring about
various alignments of the ridges prior to
their fusion, resuitinig in deformities such as
transposition.
Subsequent work on the morphogenesis of
transposition has been mainly to mnodify the
schema of Pernkopf and Wirtinger. lev and
Saphirt° and De la Cruz and co-workers'-1
thought that there must also be faulty absorption of the bulbo-ventricular flange (a
myoblastic mass between the bulbus cordis
and the left ventricular base) in transposition. It has since been showni, however, that
bulbar resorption is more apparent than real
in normal cardiac development. Shaner12 and
Barthel6 have combimmed certain of Pernkopf
and Wirtinger's torsions with hemnodynamiec
considerations to explain transposition.
Doerr13 and Goerttlerl4 have restudied the
torsions and brought more precision and
simnplifieation to the timinig amid location of
these events.
In the final analysis, cardiac development
is mainly a product of differenees in rate
anid direction of cellular multiplication, as
modified by hemodynamic and other factors.
iTorsions" and "detorsions" are but seeondary manifestations of growth anid always
raise the question " what is twisting what ?
For example, ani apparent torsion in one
segment might be due to a hemodynamic
surge in that segment or in an adjacent segmnent; it nmight be due to asymetrieally increased growth rate in the segment alid not
truly a torsioni at all, or to a displacememut
Crculation, Volunte XXVI,
Nov'ember
1962
821
TRANSPOSITION OF GREAT VESSELS
of the segment resulting from growth in
some other segment. In short, a schema of
"torsions" and " detorsions" does not identify the sites of growth abnormality and
hence can never provide a definitive theory of
morphogenesis. Goerttler14' 15 has attempted
to identify the sites of growth potency at
different regions and different stages of development of the cardiac tube by doing differential mitotic figoure counts, and has
recently extended this work to experimnentally produced congenital cardiac anoma.lies.
It is in approaches such as this that the most
useful and valid explanation of normal and
abnormal heart development will be found.
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The Embryogenesis of the Ventricular Outflow
Regions of the Heart in Man
In a general sense two principles of cardiac
tissue growth account for the evolution of
the human heart from a single, gently coiled,
peristaltic tube at the end of the third week
of fetal life into the complex, four-chambered,
multi-valved, trabeculated organ at the end
of the fifth fetal week: (1) the tendency for
inward, lumen-invading growth of the tissue
at certain regions of the primitive cardiac
tube, and (2) the dramatically different
growth rate and growth history of the tissue
at different parts of the tube. These two principles underlie normal cardiac development
and they also account for many cardiac
anomalies. Tha.t disturbances of the invasive
growth capacity of cardiac tissue result in
congenital anomalies is well recognized. Examples of arrest of this process are seen in
persistent truncus arteriosus and in A-V
communis; and perhaps mitral, tricuspid,
aortic, and pulmonary atresias are examples
of excess or displacement of this mechanism.
On the other hand, the role of disturbances
of differential growth in the genesis of cardiac anomalies is less easily visualized. To
understand this factor one must have a elear
picture of the spatial relationships of the
adult heart, the product of the differential
growth, and this is particularly true for an
understanding of transposition.
Circulation, Volume XXVI, November 1962
Figure 1
Diagram illustrating that flow is unidirectional in
the right ventricle, bidirectiona,l in the left ventricle.
The two ventricles are often regarded simply as two more or less similar pumps acting
in parallel and in physical apposition to one
another. This is of course an oversimplification. The two ventricles are quite different
both in st-ructure and the dynamics of function. For example, while in the right ventricle
flow is unidirectional, in the left ventricle it
is bidirectional. That is, while in the right
ventricle blood enters at one orifice and leaves
at another, in the left ventricle blood enters
and leaves from the same orifice (fig. 1). That
the left ventricle has but a single orifice is
shown in figure 2. Functionally, there is a
thin fibrous membrane stretched across the
orifice of the left ventricle. Blood flows in on
one side of this membrane and out on the
other side. The membrane is, of course, the
anterior leaflet of the mitral valve, attached
to the left ventricular wall at the two tubercles that indent the orifice.
This difference between the two veentrieles
822
822
rignre 2
hut
i/it
I't
lt
tl
r etticile,
shlto
r
structures', th
ttricle, the attici. end thgfr
right
the
httre
Weit
u
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foi',
inl anothier
at
cirnbryolog-ie
gpreat
tlic'
hevart ill trans'pos'ition:
of
r'ight
the
tissuie.
bulbms
the
prrimitive
anITd
r-ide
Vent
otfiter
hand,
fibrous,
two orifices of
the~ le,ft
leaflet
mitral
tlie
the
of
t'irshioiis
A-V
aiso
issue(
-valve)
('anIIal
itito
a1
Th'lins,
while
the
amidl
1rait r1al
a,
iniflowl
ue1t
:ii1d
regard
iin
Since
teinii
oni
lidis
beenl
sept:il
oi'igin11311 intro0
r-ighit ventri'iiulair
was
of
the
blll vlr
shown
to
lIe
'r-taiii
m
surface
of
the
(l
igi('
imitended
useful,
is
ini
the
1i(
utscle
e
r-i
ando
pr-esenit pa,,per-
ut
tile
usa,,ge
glt
this,
t
lti
Hle,
mist,aken.
the
wvithio
still.
is
\Virtiniger. Years
te,rcnlI
and
e
iiului1o naur
d
cu il-s,
'Plus-
deffinitiont is used 11)v ian'n Br-itish
11Fll p1l'cse'It author, bllei(vcs t
hitfilnition,
an"
and
Europe,
pdo11
AAV
tire
Outflowv parts ofr
coinpl)onieuts.
Pernikopf
Keithi gave
describe
to
the
im,,ss
of
Arithutr
Sir-
d eiet itio nt
has
miuscle
and
the.
and
thie
frour
fihwohlas"ti
-Nlli(l1
continental
Spitzir
algo
Jiiust
-its
to
uisage,
of
ig
(the aniterior'
derived
tlie trieu sp id
aortai
the
lj
t
nuiigs
for.
label
sep)arati11gr
flicUsPid
'The cristan supo axveutriculi'iis
s
tile
the
dividing
for'
i'ighrt
Oni
is
is
which
the
of
arteriosus.
tissue
ventricle
r-esponsible
dlerived
the
between_
the truneus
the
i'alleil
is
r-egioni
the
t-uLbe
by
luetweell
is
t
cordis,
cardiac
outflow
ventAricle
)Tvn
i'r'ista
friont
aird(
separated
a-re,
munscula-ture
The
twvo orifices of the right
thii
outflow
arce separ-ated
inflowN
t-ire
t-he
of
a11(1
of
basi,c
is
a-relite('ture
the inflow
of the left ventricle
('011irect ive
tin'
vessels
tt
an-d
veiit-i'icie
wihile
muisculature
Orifices
e
al of
whichl is
war.
significanice
11r1(lcrstalldirlg'
or'ifhi'os
fi
or
rmoved.
looke-d
can
tiss
singl
t
itt
tissue
-111
(iuuiPMo
t
thte
seil
i(
ls
v entricicl,
and
ait.
iss
a""d
\Aii'ica,mu
the
o
the
r-iginal
uisage
(4RAN'I ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~l~
1hIe rigitd ventricle din (dop) frorii (0 se'tv
regions of the J)riitiitie hiear-t tube, the. inflow anid outflow parts of thfe ci vctIclc1
Ie
dilevelop from twlo wvidely- sellara.,ted reg)-ions,
o f the primitive cardiac tube.. AnL1d fiere is11
one of tile baffling problemts ini limrititii i'ar'diac.
dlevNelopi-nent ho-w does. the aortca, whIiehi airise,S
f'romn so dlistal. a. part of the tube, eontire to
c('I1( mij ini exclusive anid intimrate ati a-cirwinn
wvithi the left ven-tric.le, whichl develop)s fr-ont'
the mnost proximal fpart of tire tiile ? Tire
anlswer lies in the remarkable differ-ence M.i
grwhhistorr of fib roplastice cardi,ac tis,~siwi
as compa red withi Irlyol)la-st ie ('8 rd ia t issii1e.
Thte tissuie that invafdes anlid divides the
irun-eus arter-iosuis inito aorta ahl(l jnrhrnoiiira i
airtery, and the tissue. that in-vades an-d divides
the A V canial into the miitral 11(1. ii,trsicusid
orifices are both l)alrt of a conitinulouls fibroplastic tra('t that -inies tile inner concave sin
face of the Pr1initfive cardiac- lube. It ha(,s
been shownri hr careful measuremnentf at (01(11
stagye of fetal growthi that whien this- ti~'4ssue
hias completed its Iinluen-in-vadingo g-rowtih il
the, truncus anid the A-V canial, di-vidinig ewaii
otito twvo chiannels,7 it ceases fuirthier' (xi)ailsive g-rowth.' Clessation ta.kes place. in tlhu
fifthl Week, of fetal life, When. t-Ire hen,it is
onlyr a few nirillbniieters ini size. Growth of
tire hleart after- this date is almost enttirely
due to in-creases ini the niroblastie tissut'. As,
shown iii the dliawiirg a-t thie t-o1) of figuire 3,
the lie of the coile.d hcar't tube. ini the thioralx
is suchli that the fibroplast ic tra-itlies betwi.eeni the aortie l)art of th-e trunctis 811(1 thec
miitral part of the A-V canial. Trhis mieanis
that in. the niormal heart the ao-rtie, anid
miitral rings are separated by tissue, thaif
(e(~ases expansive growth early in fetal life,
whien. the, distancie between thei two parts of
the hieart tube is Ibit a. fract-4ion of a. Itlillinictrr. While otfl(cr parts of the hecart go
tr-emen(~douisl.y tlloutsai.ds.fol(d-in tirie cilsuiit
iomithis anid years, this (listaiwerld'1'l11111s et,,,sir
tiallv the sarit' as it. vas ini the fifthi fe~ilI
wee(.k. '[it the dlitlr'IIeil'( iil growlV0 I hst Or
of various iparts ot tIre hearti i'xrlairis -why,
the(, aorta, derived frionti one end( of tIre heart
Circulation, Volume XXVI, Nortmbcr 196C2
823
TRANSPOSITION OF GREAT VESSELS
I/
Truncu
VI
A-V COM I
A- NORMAL
//ll- 1T
A
1
N
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8- TRANSPOSIrION
4_X
o~~
1,
71
\\
I/
Figure 3
Schematization of the role of the fibroplastic continuum in the development of the
heart. Top, the fibroplastic continuum at its earliest stage, when the heart is a single
coiled tube. Center, norrmal sequences; bottom, suggested sequences in transposition.
Shaded area represents the fibroplastic tract, and, at later stages, the fibrous ventricular
skeleton. The last schema in each row shows the relationship of the four orifices to
the ventricular skeleton in the fully developed heart, as viewed from the ventricular base.
tube, ends up in intimate continuity with
the mitral ring, derived from the other enid
of the heart tube.
While fibroplastic tissue separates the
aortic and mitral rings, myoblastic tissue
separates the tricuspid and pulmonic rings.
Myoblastic tissue continues expansive growth
throughout the growth history of the heart,
long after fibroplastic regions have ceased
divisive growth. This explains why the two
orifices of the right ventricle are separated.
by a wide span of tissue (the crista supraventricularis), while the two orifices of the left
venitriele are separated by barely a millimeter of tissue (the width of the anterior
mitral leaflet).
AWith regard to other relationships among
the ventricular orifices, as can be seen from
the "normal" schemata in figure 3, fibroplastic tissue lies between the tricuspid and
Circulation, Volume XXVI, November 1962
aortic and mitral rings in early fetal stages.
Because of the short growth history of fibroplastic tissue, the three orifices end up in
immediate fibrous continuity with one another, no farther apart at their points of
junction in the adult heart than they were
in the fifth fetal week. By the same token,
the aortic and pulmonary rings are also
separated by fibroplastic tissue (the fused
truncal ridges), and, as a result, in the adult
heart the two rings are in direct fibrous continuity with one another.
The difference between the two ventricles
in their outflow architecture is important for
an understanding of transposition. For example, it leads to a very simple, but axiomatic and virtually infallible principle for
the recognition of this anomaly: if the vessel
having the characteristics of the pulmonary
artery is in direct fibrous continuity with the
~824
GRANT
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anterior leaflet of the mitral valve while the
aorta is not, transpositioii is present, regardless of whatever other deformities are seen.
On the other hand, if this condition is not
fulfilled, no matter what characteristics the
great vessels have, inecluding which chamuber
they seem to be facing (or from whieh. thev
are proved on catheterization to be mainlv
draininig), transposition is not present.
For another example, various degrees of
partial'" and ''in-comolplete'' transposition
have been deseribed in the past. If bv these
termns is meant the condition where each
great vessel is partially arising from each
ventricle, fronm the above diseussioni it should
be evident that there is no conceivable way
in which septationi of the truncus caln be
complete, each great vessel in fibrous continuity with the anterior mitral leaflet, yet
both ridged by bulbar mnusculature. More
commonlv the ternms are meant to describe
a condition where complete reversal of the
great vessels has taken place, but some lesser
degree of torsioln of this part of the heart
is present. Such intermediate deforrnities
would result in various degrees of tors.ional
abnormality of the vemitricular base, and, as
will be shown shortly, there is no evidence
that intermediate degrees of torsion take
place. Therefore there appears to be neither
an embryologic nor an anatomic basis for
'partial'" or ''inconiplete'" transposition
as
currently defined.
The Morphogenesis of Transposition of the
Great Vessels
As shown in the lower drawings of figure
3, if the fibroplastic tract on the eon.cave surface of the primitive cardiac tube were
shifted slightly leftward, so that it lay between the pulmonary part of the truneus
and the mitral part of the A-V canal, transposition would result. The early cessation of
fibroplastic growth would cause the pulnionary ring to end up in fibrous continuity
with the anterior mitral leaflet. The aortic
ring would have as its only fibrous attachment a tendon tol the pulmoniarv artery (vestige of the fusion of the trune al ridges).
Elsewhere it would be surrounided by bulbar
niyoblastic tissue and therefore would end
up as the outflow orifice of the right ventriele, riding amiteriorly to and parallel with
the pulmonary arterv the classic features of
transpositioni. In figure 3, the last drawing
of each series shows the spatial relationships
aimong the four orifices of the lnormual heart
(above) and of the heart with transpositioin
(below) as determinied by actual dissections
to be described shortlv. When this relationship is compared with that shown in the
next to last drawing of each series, it caan
be seen that the orifices have essentially the
relationships predicted for them in this
theory.
The appearance of the fibroplastic. tract
w-hen viewed from the interior of the heart
is showln in figure 4, adapted from muore detailed drawings published previously.' Froni
this view, the fibroplastic tract is the ridge
of tissue froni the two A-V cushionis to the
truncal ridges. The portion of the tract between the ventral. cushion and the truncus
has been called the "'right bulbar ridge," and
considered one of a pair of bulbar ridges,
anialogous to the two truncal ridges. Suchl a
designation is misleading, however, because
the so-called "left bulbar ridge"' is meyoblastic tissue, whereas the ridge lnow under
consideration is fibroplastie. The two types
of tissue have quite different emubryologie
destinies and susceptibilities. Furthermore, in
giving the bulbar portion a "inamne" sight
may be lost of the fact that it is but a part
of a fibroplastie con-itinLuum that in.cludes the
A-V cushions an-d the truncal ridges.*
The conitinuity is important because the
*Kramer" has preseuted evidenee that there is
i1o cointiniuity betweeni the bulbar ridges auid the
truineal ridges. This is certainly true of the left
bulhar ridge, for it is miiyoblastie tissue while the
truneal ridges are fibroplastic. It may also be
true that there is nio continiuity between the right
bulbar ridge (the oine we are concerned with here)
and the truncal ridge in the literal senee of the
word "ridge"' as an elevation- of tissue, hut there
is no question of their continuity as fibroplastic
tissues. It is in this cytologic senise that the wxord
'ccontinului-?'? is used here.
Circulation, Volumne XXVI, November 1962
825
TRANSPOSITION OF GREAT VESSELS
A - NORMAL
8- TRANSPOSITION
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Figure 4
Internal view; of heart developmtent, schenmati, ed. Above, the normal heart; below
transposition. Left, before closure of the I-V canal. TVhereas normally bulbar closure
takes place in a plane perpendicuzlar to the plane of the septum, in transposition closure
takes place in a plane parallel wvith the sep,tum. The fibroplastic continuum extends from
the two cushions into the truncal septum. Middle, after closure of the I-V canal and
development of the fibrous skeleton. The crista supraventricularis is indicated by1i the
dot-dash line. The hea,rt is drawn wvith exactly the same flow relationships as on the
left, but as if all ventricular musculature were transparent in order to showu the lie
of the four rings. The fibrous continuum has become the aortic-pulmonary ligament;
it only partially encircles the left ventricular outlet in transposition. The cushions are
shown unfused to assist in orientaton but should, at this stage, be fused. Right, the
septal surface of the right ventricle. The shaded area is the region where the free wall
of the right ventricle attaches. The parietal and septal components of the bulbar
musculature, the septal (Lancisi's) papillary muscle, and the trabecutla septomarginalis
are shown. m.s.-nmembranaceous septum, showing its atrial and ventricular parts.
entire tract will later consolidate to become
the aortic-pulmonary ligament, a fibrous
structure extending from the membranaceous
septum (vestige of A-V cushion fusion) to
the tendon joining the aortic and pulmonic
rings (vestige of truncal ridge fusion). In
the adult heart, the aortic-pulmonary ligament forms the aortic anniulus and provides
a major insertion for both bulbar and left
ventricular musculature.19 Abnormalities in its
lie or development will be aecompanied by
significant abnormalities of right and left
ventricular musculature. This will be reCirculation, Volume XXVI, November 1962
turned to later, for it helps to explain some
of the ventricular abnormalities often associated with transposition.
In view of the abnormial location of the
orifices postulated by this theory and diagrammed in figures 3 and 4, a number of
deformities of ventricular architecture can
be expected to occur in transposition, if the
theory is correct. The remainder of the present conmiunication will be mostly devoted to
studying the extent to which these deformities
are actually present in hearts with transposition, and the implications thereof.
826RRANTI
826
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What growth or mnolding process could be
responsible for a shift in the effective lie of
the fibroplastic tract? The present study
sheds no light on this question. Ildeed, it is
altogether possible that the abnormal alignment is secondary to growth or structural
changes elsewhere in the heart. It might also
be asked if the shift in fibroplastie alignment
is not just another way of looking at the
torsion of the bulbo-ventricular septum postullated by Pernkopf and Wirtinger, bringing
the right bulbar ridge into alignment with a
different truncal ridge. However, this is not
the ease. In the proposed theory, the aorta
and the pulmonary artery are normally elaborated from the truneus, and the aorta is
simply, in effect, pushed anteriorly bv the
strong fibrous atachment between the mitral
and pulmonary rings. The "torsion" theorv
would have the truncus divided in an abnormal plane. As a result the coronary ostia
should have different locations in the two
theories. As will be shown, in the vast majority of eases of transposition the coronary
ostia have precisely the locations postulated
for them in the proposed theory, while their
location has been difficult to explain in the
classical theory. Also, there is no explanation
in the classica-l theory for the narrowing of
the crista supraventricularis found in all
eases of transposition. whereas it is readilv
explained in the proposed theory. Other differenees between the torsion-detorsion theory
and the proposed theory will be pointed out
later.
But perhaps a more important difference
between the classical and the proposed theory
has to do with the question, which theory better provides tools for further progress in the
field? The classical theory does not recognize
the fibrous continuity between the pulmonary
artery and the mitral valve as an inxvariable
embryologic consequence of tranisposition, aiid
it provides no criteria for recognizing at
autopsy or experimentally the emibryologic
defect upon whieh the theory is based. As ai
result. a host of differenit types of ventricular
septal defects with varying degrees of apparent '"overridingo" by one or the other great
vessel becomes "transposition. On the other
hand, while it may in time be shown that the
proposed theory is not a major factor in the
norphogenesis of transposition, the criterionl
for recognizing transposition whieh is derivedI
from this theory (the fibrous continuity 1b)e
tweeli mitral and pulhuonic rings) will conItinue to be sound, reliable, and useful for
the differentiating of transposition front other
conotruncal anomalies.
It mnust niot be overlooked that the propos.ed
tlheorv (like the classical theorv) represents
a vast generalization of complex embryologic
events. For example, the fibroplastic parts of
the primary heart tube are treated as a coiitinLumi. But truncal ridge fusion considerably precedes closure of the A-V ancd I-V
canals. And the connective tissue between the
aortic anid pulmonary rings is meature. fibroelastic tissue at a time whel, at the other
end of the continuum. the A-V eushions still
are immnnature, loosely reticulated tissue, and
the A-V valves and chordae tendineac
are seareely differentiated cytologically from
the immature myoblastic tissue of the ventricular walls. So the so-called fibroplastie
continuuim has its own differential growth.
It is a continuum perhaps onlv in a spatial
sense that all parts are destined to become
fibrous tissue, but it may not be a continuum
cytoclhemically and it certainlv is not teni-
Porally.
Material
Amongc the hearts showing congenital malformations in the Pathology Institute of the
University of Goettingen were 29 with transposition as defined above. Five of these had
some degree of situs inversus and dextroversion. Since transposition in this syndrome
poses special problems,.8 they are not ineluded in the present study. Among the
remaining 17 cases, six showed no other functioially important abnormalitv of the ventricles specifically, they had no ventricular
septal defect. The remnaininig 1I had associated ventricular septal defects; four of these
had in addition tricuspid atresia, two pulintoic atresia, onie mitral atresia, and onie the
A-V coinmunis deformity. There were no cases
of corrected transposition i:n the series. All
Circulation, Volume XXVI, November 1962
I
T1RANS'OS
10N
G'R E AT A'E SSE 1 S
8s2
-
a, )
./
I
V(3I1 (Dmar\
V
,
m
\TA
t
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m
\111,
-."
-,
Figure 5
lit
of a noli hart
'The rer trietar s(10elt0?l ox
leit) imar}ii h art w-ith h- ansjinsiiaii ( igh-t)
a iaflhate
trn li inr and, the gyreat
v ieed
(fitoti the 'entrietlar b)tisf. A )ve, tbrth
esserls trailniseetd (at their roots. Belov, cpicnrdial,Ott(at (( con ecr tive tissue hiiri been
t
the
removed doawn to the musuliatrlir aln the ftibrois rings. ihi ahimt ltrea(
mitral valqv7e hris been rem red. Yote theaft the aovitaf joins. n1ia-seiilaItarc ait thle ba(Ise of
its sinuse1(. Bl/ark threar eaii be seen tiiris1/icthe liearrs weev( siitiiredl bacl: to their
three-dinmensioalna shape.
H iearts sti. died M {ere fromii sunb'ects Awho Ilat
dlied at less thian 2 years of ag-e. Electrooardio
grams +were available for all but one case.
Architectural Changes in Transposition
Jinr its simp)lest aniatomic definitioi, traits.
pos;ition- sliouild be the condition in wihielh thi
aorta arises whlere normally tlhe pulmonar?N
arte..ry is foutnld, anxd the pulmonary artter?
alises wlhere. ntormnally the aorta is founiid
lVider these circunmstances there would be
180 -de( ree rot-ationi of the great vessels al
thleir poinlts of originl. 'Inl figu-re, 50 is sh1owvl
tlie, ventrieular base of a niormtal heart anr
ateart wvitlh tranusposition. Above, the atri;
have beeni remioved; below tlwe eonmeetive:
tissuLe structures (iitcludig tihe anlteroi
iit ral leaflet) hia-ve also been remioved. 1:
eat?. he sleen thiat in traiisposition thi.ere
itot Ca 180-de'gree c nelnoe ini the positioln o
flie great -vessels at liest onily a 9O-degre
lifferi-eitee ftrot their ioriital locations.
( irctslation0W, Volume XX VI, November 1962
For the reuttainigr eases of trallsl)oSitioll,
ani.other metlhod for stulyigt tfli lie of tltie
orifiies was used, oLe wihieh dlil niot require
s;o itrueh tlisseetion anti was imiore aeeurttce.
'Tlee niiethod was a:Ilso used for the situdy oft a
nLumber of control hearts amnoug which Were
several other types of congenital anotmaliecs.
IF me surgical wire ws carefully thre-,aded
through the circumference of each of the four
orifices, and the free enii of the wir -, approp)riately bent. to enable identifyiutig the orifi(e.
-\Viv of a (lifferennt gauge was usetd to tutlinie
mit be
otlher' vetitrie ular structureswnwhhieh
of iitterest. After wiring roe ntgcnogrcuits
were made of eachi lheart ini tw-o viewXrNs at
right gles to each otlher. The ceniter of' e'acll
orifice was establishied on eacDh filmi. miid bv
simple geometry the angles betweelle the folur
orifices were caleulated in thre-tlintcttsional
space. Figure 6 sliows a typic-al roetitoviiogratNI. A normal ltear t, a heart witl3 ti ratit-
(I~ ~ ~ ~ ~ ~ ~ ~ ~ ~'I'
~ CRAN
828
S28
NORMAL
TRANSPOSITION
1
2-
345
6
7
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Figure 7
ti/itr i fillt- otlrchitcftctft in tlifosi*1/f/jobltos oof
/
)t
iott/itof
i
tflit
or
t
1)0i/1o0. Abovet, fit fli
1t!*e)fseSl:^.7'hc auffic7 bet/ rre9v!) the)XJ{^)( o!' the
oufloulx iJhiq (z1, Me mcdM9eIe I.r is *.1, the eutrij
rlvi
c'tot iisiiit ctu)i t,
mlittit
Figure 6
i t t(I
for
' isi 1ioifj the lie of tfe ev fm
tie
fle f nwo filu?is {f-Ifobn
fr/'Cidil' trifi(icts. Otliyi
oif ?'it;lft aoltIts to etoch otter is8 sliowin. Fine wire
onutitivues eoch o) ?ifice, wifth tItiicicr wire itlongy fli
j)tosteriior snlci. Above, ao lieort if illi
onItrtor
nor ial heiart
fromt
/roinSpotisi/ion; 11nddle,
inftif ; below,
lheort ni/fh tetralogy of Fitilot
ith "oicrriding" byj the ot<orto.
Xr- o/y
one
on
a
a
w
positioi, aind a heart wvithi tetralogy of Fallot
wvith ` overridino' (lextroposition) of the
aorta arce slhownl It can be seenl that the
allngular relatioishli) among, tlhe four orifiees
in the heart withi tranisposition is identieal
withi that siowxx ini thIle phiotograplh in. figure
and1(1 the dr8awing fini figure 3, anti is (quiite
differenit from thOat ini thle norma.l lheart. On
the othier hand, in the hieartt witih teAtralogy
of Fallot witlh ''overiri(liig, the orifices ha,tve
positionis thiat (rew the Smile as in th( n1orimal
rphe simplest
wvay
to
of
onti
hieiart.
onftflot i0i9J
it ite fihet )itost cf rfliti
oti tflu otbiorniol tiitoni ce from flit
the poitif ohc.e thfi fri(unfpiti inu-i
p/ioiediit
to deseribe the
(Hif-
fer-enee ini alignmenit of thle orifiees is a1s
follows: in the heart witlh iiornoal venlitieular skeleton a str-aight linie ean be drawni
thirough thle eniters of the pulinonie, aortie,
anid triciuspid rings; ini the, heart with traitsthr'ough thle
)osition, the straightlinie
a
runs
Below, fthe tie of tfleotoflon orifice of the tight
1to1f4 rictt Tliat onylt cfoaee the pltone of tfle
ontf/toI orifice otdl flthr plne of fhe tricuspid
tilnt wa(IS ,otiistti?urd. 1, Ment iraonticrous StJ)tfulu;
,2, tricuspid ring; .3, matn tophe' seporofing ptrittot anti septot conttponents of buif)ir mvneuslttuifre;
septiti,.'6, / to'bctaa sep ft)tomi'giniiis,
t
lodtt (rtfor
enters of the ao fie, puinfiionie, aniid mitral
rillngs.
''Overriding'' l)y the aorta seih as is seen
iat tetralocy of Fallot has often been eonsid'yt> p'' of transposition. As hias been
red a 't
piointed oit prev imusly, this is niot correet.'9
The venttiieulcar skeh1't ni is fluPfltil ill these
eases, as l)roved In this roeiitgenogcrami, and(1
have' norniallv
'
thle a ortie and pulilioiii rings
loeated rigins with respect to thIe other orlifiees. Ih ''overriding,'' the aorta ''faces'' the
right ventvie Ie becautse o0f tle( particular I( (ea
tioIl of the ventricular septal defeet as w ill
be disenssed later.
WVithi biht
a
singyle exeepttion, all 17 eases
Circulation, Volume XA VI, November J962
TRANSPOSITION OF GREAT VESSELS
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of transposition showed essentially the same
degree of deformity of the ventricular base
as shown in figure 5. There was not more
than 15-degrees variation in aortic-pulmonic
angle among these eases, which is within the
range of error of the method. If there is
such an entity as "incomplete" or "partial"'
transposition due to lesser degrees of rotatioln
of the orifices, it must be rare indeed. The
single case among the 17 that did not fit into
this pattern was a case of transposition with
"single ventricle" deformity, tricuspid atresia, and incorporation of tricuspid valvular
elements into the mitral ring. Here there was
a 180-degree rotation of the aorta and pulmonary artery from their normal positions. The
reason for the greater deformity can be ascribed to the complete absence of both right
and left ventricular septal musculatures. As a
result only a thin rim of bulbar musculature
separated the transposed aortic ring from the
mitral ring, permitting it to lie beside the
pulmonary artery (but to its left) instead
of anteriorly to it.
The deformity in transposition is as if the
aortic orifice had simply been "pushed" anteriorly by the crowding of the pulmonic ring
toward the mitral ring. This is precisely the
mechanism proposed by the present theory.
It will be noted that the aorta comes to have
a position where nornmally musculature of the
crista supraventricularis lies. Interestingly
enough, this is also the location of the right
aorta in the crocodile, as Spitzer pointed out.
He was aware that there was not a 180-degree
reversal of position of the orifices of the two
great vessels in transposition. Pernkopf and
Wirtinger postulated a 180-degree rotation,
although many of their figures show no more
than 90 degrees. Subsequent authors have
often recognized that the rotation is less than
180 degrees.
Such an abnormality in the ventricular
skeleton should be accompanied by predictable changes in ventricular architecture. In
all cases studied this has proved to be the
case. For example, the plane occupied by the
outflow orifice of the right ventricle should be
Circulation, Volume XXVI, November 1962
82'3
more nearly in the samne plane as that occupied by the tricuspid ring than in the normal
heart. By the same token, the plane occupied
by the outflow orifice of the left ventricle
should be more nearly perpendicular to the
long axis of the left ventricle than in the
normal heart. These two alterations are diagrammed in figure 7, and were present in all
cases.
Another predictable deformity, presenit in
all cases, was the narrowing of the crista
supraventricularis. In the normal heart, the
shape of the septal surface of the right ventriele is roughly triangular, with the posterior cusp of the pulmonic valve at the apex
of the triangle (lower left drawing of fig. 7).
Normally, the distance from the diaphragmatic border of this triangle to the membranaceous septum (spanning the tricuspi(d
orifice) is relatively equal to the distance
from the membranaceous septumn to the pulmonic valve (spanning the width of the crista
supraventricularis). The ratio between the
two distances is roughly one. In the infant
heart and the heart with right ventricular
failure (and consequent dilatation of the tricuspid ring) the tricuspid measurement is
greater than the crista supraventricularis
measurement, and the ratio is increased. Interestingly enough the ratio is also increased
in marked left ventricular hypertrophy.* But
*There are perhaps sound enmbryologic reasons
for this. The two ventricles are in physical continuity with each other in both their inflow anid
outflow regions along the initerventricular septum.
The inflow part of the septum (the width of the
tricuspid orifice is a measurement of the inflowv
region of the right ventricle) is developed by the
downward growth of the two ventricles, so there
is a rich anastomotic m-iuscular syncytium between
the two ventricles in this region. On the other hand,
the outflow part of the septum (the width of the
crista supraventricularis is a nmeasurement of the
outflow region of the right ventricle) develops later
and is due to the bulbus cordis f olding over the
base of the left ventricle. The anastomotic muscular syncytium is much less abundant in this
region. Therefore hypertrophy of left ventricular
muscle is less readily communicated to tbis regioni
of the right ventricle than to its inflowsr musculature.
S30
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in these coniditionis the ratio is rarely miore
than 2 :1, and they are easily recognized on
other grounds. Among the eases of tranispositioIn studied, the crista supraventricularis
measuremenlt was never more thaii a third
of the tricuspid measurement. This narrowing
of the crista can be seen fromn the drawings
in figure 7 anld the photographs of hearts in
other figures.
The narrowing of the crista supraveintricularis was studied in greater detail in the six
h-tearts with transposition with no ventricular
septal defect in order to determin-ie whether
any specific bulbar muscular components were
absent to account for the narrowinig. While
the hearts were too small for extensive disseetioln, all niormal hulbar comlponenits (as described in referenee 19) were present in these
lhearts but they were thinner than normial anid
there was marked overlapping of the more
proximial coinponents by the more distal components. Indeed, the trabecula septomarginalis was often nearly hidden from view bv
the overlapping bulbar musculature.
The right ventricular septal surface was
altered in still other ways bv the narrowinrg
of the crista supraventricularis. Normally.
the posterior cusp of the pulhoniie valve is
plumb with the right ventricular septal surface. The imiedian raphe at the base of this
cusp (a landmark between the parietal antd
septal bundles) is in the midline of the septal
surface. In transposition., with the right ventricular outflow orifice drawin nearer the trieuspid ring, the right ventricular septal surface is, in effect, rolled anteriorly. The median
raphe is nio longer median and comes to lie
along the left side of the septal surface, with
the so-called septal bundle ofteni becominig
part of the free wall of the right ventricle, as
showni in the upper drawing of figure 7. Incidentally, the shift in the position of the
median raphe is fuirther evidence that it is
not a line of closure of the bulbar part of
the I-V canal, as lhas sometimes been suggested in the past.
Any theory of transpositionl must explain
the lie of the coroimary ostia. According to
G3RA(\RANT
the present theory the two ostia should be
found in the two aortic sinuses which lie on:
each side of the tendon connlectinog the aorta
and pulnmonary artery, as diagraimned in figuire 3. It is necessary to define their location-s
in teriis of the tendon joininig the twvo great
vessels because this tendonl identifies the
plane of fusioin of the two trunieal ridges dividing the truncus arteriosus. In the presen-t
theory it is assuimed that truncal septationi
proceeds normially? in which case the ostia
should have the same relationiship to the tenidon as they have in the niormal lheart (also
shown in figure 3). On the other hand, in
the torsion-detorsion theory, muost authors
have postulated that two otheu truineal ridges
f use to divide the truncus; therefore the coronary ostia should have an altered relationiship to the tendon. In all but one of the 17
cases in this series, the coronary ostia were
as predicted by the present theory. In the
one case, both ostia arose fromn a single aortic
sinius, the one that is adjacent and posterior
to the tendon.
But, it muay be protested, if we accept this
interpretation for the lie of the coronary ostia, they will have exchanged with each other
the region of the heart they each irrigate.
To meake this clear, let the reader imagine
himself at the center of the aortic orifice, facinig the aortic wall where the tendon to the
pulmonary artery attaches. By this theory of
transpositioni th e ostium to his left, which
iii the normal heart leads into the left eoroniary artery, now is mainly irrigating the
right ventricle. The ostium to his right, which
niornmally led iilto the right coronary artery.
im transpositioni is mainly irrigating the left
veentriele. One cami only point out that little
is kniown about the determinanits of the lie orf
the coronary arteries beyond their ostia.
Nearly certainly, genetic and other encoding
factors will play a less and less important role
the farther one moves down the corollary arteries fromn the ostia, and local factors will.
beconme more imnportant determ-inants. It mnav
well be that c-oronary arteries temid to be elaborated, as are experimental collateral arteries.
Circulation, Volume XXVI, November I962
8I1S
Tl{ANSlt0SITION 01F (G REAT AVESSELS
831S
j I | 11 l 0 /, <1 -1t -0-0---5I
'I
.-.,.-.--
Figure 8
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i. 'l7e heart has a
(
1)isplacetnent oj the left venutluor rg if;ktio.i
large veitricular septal defecit. the incision. prtends front. the right ventricle, across the
septum ovller the (defect into the left ventricle, Nhowing the ri'ight ventricle commlinunicating
thr ough the defect iuto the outflow tr at a! the leftfen tricle. The inembrnanaceous septum
ties inmoediately behind the chorda extecuding from tlhe smnlall septal (Lancisi's) papillary
minuscle to thte ctiterior tricuspid leaflet. Note thle distance fronm this point to the left
rentricular outflow cusps ( punttonici. AYointltty th letuft rentri -icaur outflovw Cusps
(aortic) cross the membranaceous septtt in at tbout the stme point vithere the tricuspid
ring crosses it. 7, Aorta; 2, outflow trail of tfhe igight centriule; 3, tricuspid orifice;
4, posterior leaf of the tricuspid valve; 5. pulmoit rl arterY;: 6, rig/it att riot part of
inemb ranoceous septuin ; 7, septal papil/lo n isnciisle.
from t-he vasecular soliree thiat is niearest the
tissue to Ie irrigated. In aniy ease, this is
whiat is suggoested as taking place in transpo-
clh<aniges iii thlie mnciubranaceous seJ)tum were
inoted whliel ar-e of initerest: (1) While the
portion of the meumbranaceons septum that
sitioin.
Thie IIost intere,sting(- anid perlhaps the most
ilpl)ortalit chiangoes are those related to the
inebnranaceous septium an1d the aortic-pulmiionary Ihganmect. Tlie imembranaceous septumii
is difficult to describe aniatomically. Tt faces
a-ll fouir chamanbers; it formis part of the marg in of three orifices anid. is continuous withl
thliree valxve sv stems; and it provides insertioni
for botlh rioght anld left venitricuilar imnsenlatuire and also for both right anid left infunlilibular mnuiseulature. Thus defects almnost
anywhere in the heart will tend to hav-e somne
effTet on-i this structuire. ('uriousi>x e!noughl
th.ere hias never been (a detailed stuidy of its
norimial architecIture, and( we know little about
its enbryoloy(v l)yevonI thie faet that it-, is on1e
of tthe products of the A-V ctuslionis. I)oerr18
hlas.; emphasized its crucial, fuleral position
for cardiac ilor)hogceiesis.
In the hearts with tranisposition, two
se/-)rate's the left ventriele fromr
Circulation, Volume XXVI, November 1962
the right
atriumin tra1sllniui. atc,d well, in all but three
cases of transjposition, the por'tion separatincr
the righlt anid left ventricles transillum-linated
irreg-ularlv, if alt all. u'lie opacification proved
to be due to a layer of left ventrieular muscle
overlyhino the left suirfa(cie of the mnembrana(oluS sepAtui. One can1 only guess that perlumps this mneans thliere is a displacemnenit
M ferio rly of left ventriuenl ar musculature,
wihdich normally inserts on the aortic-pulmoniarv teindoni. This was the first evidenice that
there wvas ani albormality of left ventricular
niuiseiilature in. transposition. (2) The portioni
of the inembranaecous septumn separating the
right atrium front the left ventricle was usuallyv inecreasedl ii surface area in; the eases of
transp)osition. This is best seeni by comparingZ
wivhere on its ri(ht side the tricuspid ring
crosses it, wvith wlhere on its left side the aortie
culsps cross it. Normally, the tricuspid ring
832
GRANT
234 -
120---
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7--
Figure 9
Architecture of the right ventricular outflowu region. On the left, the left ventricular components
are shown; on1 the right, the bulbar components
that overlie and are continuous with the left
ventricular components are shown. Top, drawings
of the heart as viewed from the rentricular base.
Center, the same heart is viewed from the ap,ex.
Bottom, the right ventricular outflow tract in the
large bulbar septal defect and "overpresence of
riding." (a.o., aortic orifice; m.o., mitral orifice;
scle (the bulbospiral bundle);
I, left ventricular
2, ao rtic-pulmona ry liga m ent; 3, membrranaceous
septum; 4, lateral tubercle of the left entricle;
, pullmonic ring; 6, tendon from aorta to pulmothe part of the membranaceous
niaary artery;
septum that separates the right atrium from the
left ventricle; 8, tricuspid ring; 9, crista supra,ventricularis; 10, median rap,he separating parietal from septal bulbar muscle bundles; 11, lower
m>a}rgirn of trabecn la septoma rginalis; 12. modcvatoir band.
a
mu
7,
erosses the miiem:lbranaceous septum almost
directlv opposite the lie of the aortic cusps.
In transposition, however, the pulmonary
cusps often lie far distally from the lie of
the tricuspid ring, as shown in figure 8 (and
diagramnied in figure 7). The explanation for
this is not known, but it is as if the fibroplastic
continuu:n, which holds the pulmonaryriinog to the mitral ring in transposition, had
been strenuously opposed at some date after
the completion of these structures and stretching of the pulmonary attachmnent had taken
place.
AVith regard to the aortic-pulmonary ligamaent, normally this structure is at the line
of attachment of the aorta to the left ventricle, encircling the outflow lip of the left
ventricle from one tuberele to the other and
therefore anatoinists call it the aortic annulus. It is continuous with the membranaceous
septum and also gives rise to the tendon connecting the aortic and pulmonie rings (fig. 9).
From the enmbryologic point of view, it appears to identify the line of closure of the
bulbar part of the I-V canal and therefore is
a principal expression in the adult heart of
the fibroplastic continuum which extends
from the A-V canal to the truncus. From the
point of view of heart function, it not only
provides the main insertionl for the musculature of the left ventricular outflow tract
(principally the bulbo-spiral group) but also
for the musculature of the crista supraventricularis and for certain of the intrinsic
muscle components of the right ventricular
outflow tract.
In the presence of transposition this ligamerit is shortened (corresponding with the
narrowing of the crista supraventricularis)
and only partially encircles the outflow orifice
of the left ventriele, as shown in figure 4. The
shortening is apparently due to the fact that,
wixith the pulmnonary ring drawn closer to the
mitral ring, the plane of division of the truneus comes to lie much nearer the tricuspid
ring than in the normal heart. It is difficult
to see how this deformity could have been
predicted from the torsion-detorsion theorv
of transposition, yet it is perhaps the most
important deformity of the ventricles in this
syndrome, for it results in certain deficits
of left ventricular nmuscle in transposition.
These deficits can be seen in the external
shape of the left ventricle and may be responsible for the ventricular septal defects often
associated wvith transposition.
Circulation, Volume XXVI, November 19~2
TRANSPOSITION OF GREAT VESSELS
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The alteration in left ventricular shape is
shown in figures 3 and 5. When the heart is
viewed from its base, normally there is a
prominent "shoulder" of left ventricular
muscle immediately beneath the left margin
of the right ventricle. In transposition this
prominence is no longer seen, and the musculature of right and left ventricles forms a
smooth left border. The "shoulder" is made
up of muscle that inserts on the aortic-pulmonary ligament.
Regarding ventricular septal defects in
transposition, 11 of the 16 cases had septal
defects in the outflow tract of the right ventricle. One had, in addition, the A-V communis deformity. In all but two cases the
septal defect was distal to the trabecula septomarginalis. (In the case with the A-V communis deformity, the trabecula septomarginalis separated the bulbar from the communis
defect.) Of special interest was the fact that
in four cases, when the defect was viewed
from the right ventricular side, it appeared
narrow and slit-like, parallel with the trabecula septomarginalis. When it was viewed
from the left ventricular side, it was round
and large. On careful study of the bulbar
musculature in these cases, all normal bulbar
muscular components were present. The defect was narrow and slit-like because normal
bulbar elements overlay it. Thus, in these
cases the defect appeared to be due to a deficit of left ventricular musculature in the outflow region. The bulbar musculature was
normally elaborated but apparently could not
fuse across the deficit of left ventricular substructure.
It has been pointed out previously that iii
the ventricular septal defect of tetralogy of
Fallot and other syndromes unassociated with
transposition, the septal defect appears to be
primarily due to a failure of certain bulbar
muscular components ever to develop.19 Perhaps in the ventricular septal defect of transposition we have the opposite mechanism, a
septal defect due primarily to a failure of
certain parts of left ventricular musculature
to develop. If so, it is very likely that the left
833
ventricular muscle failure is due to an absence of adequate insertional tissue, manifested by the shortening of the aortic-pulmonary ligament. It must be pointed out that
not all hearts with transposition and a veiitricular septal defect showed this " pure "
left ventricular muscle defect. In at least
four cases certain bulbar muscular components were also absent in the region of the
septal defect.
The shortening of the aortic-pulmonary
tendon means that the main ligamentous
structure for the support of the outflow tract
of the left ventricle is defective in transposition. It is little wonder that a wide range
of different degrees of "overriding" by one
or the other great vessel niay be seen in transposition. They have been given a number of
different names on the basis of clinical findings, (Taussig, Bing, etc.). WVhich are due to
defects of the ventricular skeleton in transposition, which are simply large ventricular septal defects, and which are due to still other
embryologic defects is not known. One of the
more important problems now facing pathologists and clinicians alike is the sorting out of
these conotruncal syndromes and developing
objective anatomic criteria on a sound embryologic basis for differentiating them.
The Ventricular Electrocardiogram in
Transposition
There were 12 cases of transposition with
or without ventricular septal defects but with
no complicating inflow abnormality such as
mitral or tricuspid atresia or the A-V communis deformity. Eleven of the 12 had essentially identical QRS electrocardiograms: the
mean QRS vector was directed rightward
superiorly and more or less plumb with the
frontal plane. The QRS loop (plotted from
the conventional tracing) was narrow, with
its major magnitude in the terminal segment.
Whether the loop traveled clockwise or counterclockwise depended upon trivial differences
in spatial direction of instantaneous QRS
vectors (fig. 10). In all cases there was some
degree of QRS prolongation for the age of
the subject. Thus, the typical QRS electroCirculation, Volume XXVI, November 1962
GRANT
834
I
I
I
I1
Figure 10
spailtiatl QRS v ector and the frontal plane
Q RS loop in the typical case of transposition.0t
Mean
plotted
on
the tri-acixal reference
figure.
SI S283-to-S1S2r3 pattern.
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
'I1his QRS finding is quite astonishing in
the liht of the anatomic findings described
above. For nmanv years electrocardiographers
have attributed the S1S2S3 pattern, when
fouind in abnormal hearts, to hypertrophy of
the crista supraventricularis,* because this is
the oimly part of the ventricular heart that is
"facing"' the right shoulder. (Electrocardiographic theory has always held that a giveni
QRS vector tends to be perpenidicular to the
veentricular wall from which it is generated;
ill the
patternl, the QRS vector poin-ts
toward the right shoulder.) Indeed, it has
oftenl bee-i called the "crista supraveintricularis pattern." Yet one of the most striking
differences between- the heart with transposition and the normal heart is the remnarkable
X aduction in mass amid surface area of the
crista supraventricularis in transposition. Nor
cloes attributing the QRS finding to right
bundle-branch block solve the paradox, for it
still remainis necessary to explain why the
terminal forces are directed rightward amid
sl1periorly instead of rightward and iniferiorly as in the usual case of right bundlebra-tich block.
There are two possible ways to solve this
dilemma. Perhaps the electrocardiographic
theorv is incorrect which postulates that a
QES v-ector is perplenldicular to the region of
515253
thla
eiista supraventricularis iii its origlual miieaniiig: for the portioi
of tissue that lies between the tricuspid and piilmaoic rings ai-d against which the aorta curls.
Eleetrocard iognplliers
have
aire
mtiore
tused the term
Circulation, Volume XXVI, November 1962
orthodox
1)odY.
A secon-d possibilitv, coinsistenlt with elec-
car:dioorami in transposition teinds to be the
p)athologists ati(l
the venitricular wall where it is generated.
It must be admitted that the postulate rests
entirely onl theoretical colnsiderations, phvsical and mathematical calculations of the distributioni of an electrical field arounid an open.
non-biological generating surface. The author
knows of no experimenits demuonistratinig thlat
this principle is true specifically of QRS
forces as recorded at the surface of the tuim8an
i
trocardiograplmie thleorv, suggests that thie
miiean QRS vector ini transposition is actually
the resultant of two other inajor vectors haying differenit direetions. For examnple, if there
were a mean: QRS vector generated froml the
left venltriele wvlhielh had the direction of
mlarked left axis deviationi, and another m-eani
QRS vector generated relatively simultaneously froin the right ventricle with markecl
rihlt axis deviation (perhaps parallel withthe lead I axis), thIe resultant of these two
v-ectors would have the S182'. (lirectioni.
There are anatomiie features of transpositioii that imiake this "resultanit" explanationi
of the QRS axis plausible. First, the left
ventricular imiuscular abnormality of tran-spositioni is precisely in the region of distributiotn
of fibers from the anterior division of the left
l)ulLdle branieh. It has beemi slowmi both cliiiically and experimentally that interruption
or danmage to these fibers results in left axis
deviation.20 F-urther indirect supportinrg evidenece is found in the three eases of transposition which had, in addition, tricuLspid atresia.
It is well recognized by electrocardiographers
that tricuspid atresia is associated with left
axis deviation. Whliether tIme left axis deviationl is due to hlypoplasia of the right veentricle
or to a left venitricular coinduetion defect will
require further study. for either is possible.
To appreciate how deformned the ventricular
lheart is in this syindroime, onie nuist studv it
th ee-dinmensionally, as shlowni in figure 11. It
canl be seen that only a sm-all part of right
veintricular inusculature is presentt only the
bulbar part. There is nio vestige of the part
of the right ventricular mnusculature that develops from the trabeeulated region of the
TIiA\SPSITIONOF (;IiEAT
J)i'l.ii'>MF l1'Ieatl t7411) (thle liec XXvall
in floXv 11811
foliilll(l. -Is
835
3
ESES
anti tfle
118e 1 ft vecoti'jell lS 818(1 deWXalI is ('0l(idSillal>v
jIO)Stlc'iOi
it
thleue is 110o ai-.~-isilliin illalal-~lie( men,i1raiiaeea)iis
s')l11181, illd tat il-g thiaI hie're is also anl ali
il0lli'iiia!,itv inl 1111 ig-lol of the1c l)athXXvay o1 tIn
Iniridle ot, IN S. Ill anyv cvxcot, it is (fuite- elear
I alIhere is no slihstanlt ml rigid. veiitricuflar
rfigtXXvarl (QR8 vee
10' HIn these eases. As a result, cveii t1loiongl
I iA IiPsl)Iitioii I s pII-s('ilt-, oiie, Wvohild eiPIlt
11)(S1 ('8515e 111 5,110W. 0111¼v Jellt 8IXI5 devicatioii
elhiareter'isl ie. of triilSJIild atresia. '['hiis pIrovedl
to1 11 51). AlIl thrcee showed the niarked' left
axis deviatioii eii'aeaeleristie, ofI tri cuspid
atrelusa XXvitliont aIX dIisceri1lille effect frmnII
iiisilai111to1
1(1
JInovXd
1
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tr'ini'Spositionl.
It, l1(011-ld(1 lIe Jilltel1 oLt' that tratisp)ositioii
1 he
nlot tileI onlV (eauise of tile SIS283 pattern.
it Iils senl. inl othier congoeniital- heart anomtalies
(althioughf i)rol)a1)ly 11(11 tts reg-ularly), aiidi
is
inl aet,(uireti right ¼'vintrieular hypertrophy
ywliere perhiaps it is dite to hyper,t.trophy of'
thle e,rista spaitrclrs ltothproof
Is, still, xvanthing). anid it is eveni seen occasiontill>v ii perfectly- normial sull)ects of any- age
grouMp.
Differentiating Transposition Anatomically
from Other Conotruncal Anomalies
There arc,
anomialies that often arc
(hiffielult t-o differentiate fromi- transpositionl.
)nie is thie larg,e bvilhar septal. lefect witli
twxo
(dextroposition) IbX
especialiX i-f thc- puhonioe, oriflce is
ii1ark~ed ''(IXverr.iding
1 lie aorta,
smllall. TPLc othier Is persisten.,t trmumnis arteriosois andi( its varia-ltls sueti as 'pseudotruncus.'
s i traiisposition.,
In-1 thlese cond(itionls, not
erista
suipravciitrioIdaris ma> lIe Tiarflie
roved, flhe aorta appears to he takiiig' OtIf fr-ont
tlle rigt Xcitricl e,nieinbranaeeoos septumt
relationshipvs are ahoornial, and tie. left yenI rien181iarmscoflatutre is, oftenl deficienlt (fig.1 21.
hO ftic'i iiidIiXv a lcarge iulhlar septal
d tIect cani resenible trallspositionl, it is nlece's
sarv- to nmiierstaiid thie aniatomny of the righit
vllitricular ouitflowv region, diag-rammied ini
C'ircuhlation, Volume XXVL, Novemrber 1.962
A,
p
/W--l<
-
..(
p
}
Ow6
(V.
-OAf
Figure 11
h1(111tSis 4o'ui
t1(ilt
('ot' cftmjIOrisof.
oil the (lt
Y'(IM0y Il ljlllth,i)lrl
ritci/ld
d
Alit
joh'
InI(st/-I (1111t r/I
p11(I1.t
li/l
Ofbiio'
00/l/
dillicit0/0/Olc iml/lf Icl Theiio'tldiii
$ 11(1
t h 'l
t1)(
11
7/ie
/)(
(tilt vcltr'
't fc 'a
2r
If t is (I siltII
fly
OC 'lrce /i
figlnee 9. \Whlill the righit veltriiuelar tIiu1seluhat ure is gro1sslv a sync>vthim. tXwo layers (If
dliieetiomiat alrays (If muiscle caim lIe ita,de out1
[ii its oOtfloXv regolio. 'Vlie m,ore smuperficial
Ia>eIT cnsists (If eoinpoiieents that ins-'ert oIii
thle ImIl(imilie ring(. Thiey pass across thfe scl)-
ald surface (If tlil righit ven~tricle, eithler to
merg-e XX itli r-igit venltricul'ar free waIl 11(118t'ulatiuri or to hecomne a part o-f thec trah)eeilca
septomoarginialis aiid thie ii()(erator Ilaild. 'j'li,
deeper, thicker layer c-onsists of coIil}oliellls
that inisert oni the aortie-hltiilotiary' lig-amneit,
xvlere left -ventri(ucular olltfl(IX ilulseulatuiir
and( erista siipravelitriclllar-is musculature
also inisert. It appears that builbar sehltal dlfeets are duie to the absciiec (If certaiiiClli111jonleits iii Ilotli lavers of bulbar musculature. il
'Phll deficiencyv in thie suplerficial lax-er determinies ivhiere iii the liuilbar region the(, defect
wvill lie whlile the deflictien in thie deeper
laxver deternijules howv large-( till defect xwili ho.
WVithi large hulbar diefects, nwarlv all of thie
deepIer layer miay he ail.seilt. Fromi the e,mh.rv>
illogic. poinit of viexv, t1fis meanis that the lateral ridg~e of inyoblastie tissue failed to) fuse
S3(;
8GRAN'I'
t/
4
3
2-
?
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Figure 12
lfe mc it
fro cii
cvit/i ptl
v
the
i
o/t
s/co
cm0/tf rI/
S
t//it
ieniocc.
is
tte t tilclctis
tic
/l
att1(1/, to
1, A tcorior m
t rcc
n
wtcf 3i
,
r1ttr1joscc.8n
in
/st.
i ste'
f/t
citrcci
(tion
uo to
f1t rn
l
cci
itccflt t;
se
iel wed
//hii
h
the
iit
ii
9,
left
ftacl b/undil/e
cci
ture;
i/i //Sci
t t ic i/i t/i ildi
titherigh
i//st Ftititn o f rig iht cetctiit //icr free ival/ l ///sculat/te
( l/(1 01/h/i. bidibitir P///scle buntdleits; 5, riIghct c ooi iorcq
c//It /7/,'I;
a; singlIc poic t of ijnls ,tion oft ecistic
t 9)tiit ci l 'icc
1 csc
I//it; 7, intsetti ni of
o n
Inclcu
i i
fn ser'tiOn o f lef t
ic-
o
1,
,
o
i
thfe fibroplastie, cointimcuuitm. Witlh n1o
Iculbar
I
nuisculature ini the ouitflow regioi], the
left venmitrie l ar mn use inl ature is inc apable of
growingr across to mieet time aorti- pulniouiary
li'ia,11nent. and the defect is- 'throuAgh and
throug-h. Withi neither righlt nlor left vemi'
tricular septal miusecilature mneeting, the aortic-pulmuconary ligamient, the only miusculature'
inse,rti omii t1e li(gament an-d mieefting the lip
of the aorta is t h-e crista sutpraventricularms.
l1int this mn-useculature belon(,s strietlyN to time
free Nxxall of thei rigiht vemitricle. As a result,
the aorta is suispemded anteriorly, solelv bv
the free wvall of tIme rigfht venitricle, aind thlis
is the reason xxhy, ii '"ox erridling, the aorta
apl)ears to origrinate fromn. the right ventlriele.
TPhm're is nio abniormiiality of the venitricular
skeleton. 'T'ine ahbrormnalitx lies in the elahora
tioilm of bulbar muscuilatutre. Thlerefore thie,
wxav to (ditefrenltiate it fromti transposition is
to see if the ventricular skeleton is albormnal.
wvitlh
'l'llis is miost sillmply (11on ly seeing whiclh outflow orifiee is continious withi the anterior
itral leaflet, as poinltedI out earlier.
LIn the large venitricular sept)al defect tlie
mitral auid triduspld valve surfaces are often
conttiniuous wvitlh eachl otlier. Such a defect is
some(-t4imes explained as due to "absenee'" of
thie nnl.mbranaceous septuim. But if it were
truly ahsenit there would be free counnunieatlion between three, anid perhaps all. four
chalibl)ers. Tt is imiiportanit to remteibler thilai
anatomically the nieminbratnace-ous septum is
b)ut aii inisertionial tenidon foir atrial anid veiitr-icular mi-useulature. Wlhten a given region
of museulature fails to fuse wvitlh the fibroplastic con-rtinuum, it does not develol) its
tendon, and that part of the mnembranaceous
septuim will be absenit. In tle large ventrien
lar septal defect it :is usuially the musculatiure
of the trabecula septomargiincalis that failed
to mtteet the fibroplastic conitinuuim. 'The tetn(loll for this musculature is the part of the,
tciemlbranaceous septum separating tle two
ventricles aiid separating the mnitral anid tricuspid riligs valve surfaces. But other parts
of the miemiubraiaceous septum are usually
present in. suclh cases, notably the part se,par atingo the right atriumn fronti the left veciitricle.
Iii the heart withi tranispositiont. aiid a large
ventricular septal (lefect, the mitral anid tricuspi(l valve surfaces muiay at first appear to
I)e- conltinuous. Ilowvever, oni closer study of
all suelh cases in the present series, there was
founid a slenider banid of left ventricular musdc extenidinig to the pulmonie, ring and separatin, thee imiitral and tricuspi(d valve surfaces. Thlis is illustratetd in figure 13. This
is apparently the sameIleft ventricular mnuscle, described earlier, wllich oxerlies the mcemItlrwaiaceous septumi in othier hearts with
tranispositioni. ini this lheart it extended precisely to the reg-ion between the outflow cusps
wlxere normiially the interventrieular part of
the menibraniaceous septum lies. It is iriteresting, thlat the abn-iormal or (lisplaced band of
left ventricular musculature hlas sueh growtlh
primacy that it will appear even in tihe abCircutlation, Volnune XXVI,
November 1962
1
VESSS ELj S
TRANSPOSITION(O)F GIREAT
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(Iltf tof tllis part otl the neiiltrlanaceous
seeptum.
lRegar(liig "'tructies,'" it is onilv possihie
i 1as)pets that relateot
here to discussx ((tlan
the vejitrieular skeleton. Whlile. (eclassical
is rea(lily recognized at autopsy>
t ni Iies
C
soneitinies it is dfifficult to h)e sure that the
pulmionary artery is ahsent, and oecasio)lllly
thiere are oiilv three olutflow C11J)5 (resinp
bliliig an aorta) instead of fotur. Buit even ini
the classical ease one, muitist determttine if tin^
skeleton is otherwise nioormYlal. When the fibirons andcl imuseular struetures attaehiing to
the truncal ring, are stutdied, eertain of them
reflite to the aorta, others to the pulmrltoiiary
arter>-, certain are left ventricular, otliers are
r ighlt ventricular. r11ie plane h)etween the two
group)s will indieate thie planie in xx Inelh thle
dlivided if further develz
trnclcus would have,
oJ)lllt had taken place. Tph1el heart shown i n
figure 12 is a classieal cset of lersistellt truniens arteriosus,. It ('al hie seen that thehlalf
of tIew truneal ring- xvitli coronary ostia is
cointiinuous Aitlh the anterior leaflet of the
mitral valve. Since thie aortic part of the
truneus adjoins the miiitral valve, the trtncal
ring is in niormial p)ositionl in tlis ease. Faill
tire of tile truneacl ri(lges to fuse is its oni>
skeletal ahniormriality. However, nearly eelltainlv thiere will be eases of 'truncus?" withi
tle transpositiollal deformity of the velntriclar Skeletoll, tile )ullllollic part of the truniical rillo eolltinuou's with the-}aliterior- miiitral
leaflet.
of
septal defect with pul
In eases houl.bar
ittoiiarv artery atresia (often called '`pseilotrutlleus bv the ehliciian) the ventricular
skele0ton is ittore (ifieult to appraise liecause
pl)llnonary' valvular eleinents are abselit. One
mig-ht tllillk the preseciee or aibsenee of trans-
position: could h)e deterlntined in(lirectlv. That
is, if the aortie rilcr is hiot conltilluous withi
the aniterior imiitral leaflet, the pulmoniie rilig
(Ilowever vestigial) mnust he. But this is niot
neeessarilv the ease. Neufeld, Duislhane, anid
Edwards2' have deseribed a groul) of eases
that bear on this under the title 'Origin of
Bothl G reat Vessels from tle Right VYeiCirculation, Voltmec XXVI, November 1t962
Figure 13
Ainomalos it I't ientit cidt/t ttisct e in titt t's )s'itio,t, cls)e:-up2 of'( h c (sfrtsIf -h at /<lar.ty rentr ilcW(IrS
son/til0 d/iletct in itfiitt/on to finnspnosi/imn. Titv
cif s
nineinno njft/i t J / 0/ll.fches
terit( ini' tic|dt
the Jlnni' n/ 1h/i defect nf let -ncr
c
t es j,)t!
n t c(I
h , t)
fi' iJ
)trip n f i eft r. c f tficui/in*
t
On1
btecift ninocci.
fith initi'tti itnd lciiitspid 'ti/ic strf ('tic ts.
po)02tion',- a.1r, axo tliC
ottnieitit-iial
rIt/ce c itsps;
nt'.p it/tm icti' it
rmfin
t.v'.n tr ict.ispid vl ves!, ,9.p}fat
?
r'ct/e; anomtm
ni mS'cc,
t
e
sti'i nt/
(J 1
t Ic'cr
iCi'u/ctr
musole.
tricle.'' (To bie
sure. am1ong
the 11 eases
ie-
l)olted terew are three ii- which the aortie
ring was in fibrous eontiu-tity vitil the anterior nitral leaflet. ]While the A-ord 'orioill
1ny.a1, differenit mileanligs, frol ani
mtahavl maae
anatonic anId enllibtryologicj)oiit of view, (iie
imuiist collclle tlat in. these three eases the
aorta `originiated` wvith- the left venltriele
LI(l nIot wi;thl thle r'ighlt/.) Nevertheless, ill
thel reinlaillillg eases there is 110 dlount that
neither the aor}tie( iior the pulmlonie riilg) Was
il fibrous eonltiillitv w\itlh the anterior nitral
le a fle t.
'liese ecases are extremely ih portamit, fol*
they represent a rieviousl>' un1knoNvi tVp)e (f
coiigeiiit-all lalforlaiitiiLl of the veintricular
skele,ton. TI(o interpret thenti in thet light of'
the emlbryolog(ic shemiea deserihnd ahove, evilulnu is illter'
dleitlv thle fibroplasti(e coiti
ruptetI by iiuse 1ulature tlhe fihbroplastie
proeess dividing fthie truineus is 110 loniier con-
838
8",38
tttihll0tellt ot' the p11110(1
iamry art-Ierx lax lbetxweeii the ilmlie and( mi'trl.1
t
i'tilSpSitOil
4,
pa.
ant.
I
Figure 14
it/
tI00110/ lit
JI1)uscti/or scp)lotIlo/1o
)
]'oln
isoith: ou11o It otifit 1c5 ino ttatsposit ion. -Thtre -i's a
/ hot(pid
ttot
volI c1 810f ((to tII,,
Itc cittittIIl
c
o
coo t ill 1)01IS ; 01i/itIIri
of tile tOt )-
otitj.)o-itttt
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
1111118.C(H xvilp hew c(In(e5 (lenit (ugtheA
canal1. Since iio. par't (If thle trttiieus is iieldl
to theo mitral ring- hy a tiltrotus attaelniiemit,
thie left xonttriele never acquires a truliial
outlet. And(l wxhein tie, truncus ffiiilly dixvides,
it- siiiply- providles tie, b-tlbius xx-itb txxo otitt
lets xwlhere formeriy it iicad bu-t one. T1lw imrl
alle! I uhel)(s -becomne the ''douible outlet*" fo
thrgh
ellitr (I(e, a teo.ru WNithatu112 inijro_
arc of so1111i'
for
tllev
explain wliy there, are
iiiportaiiee,
outlet"
righlt veiitricle lImit
oaes(f ''double
huolbalfhy there xwiii never be described (cases
of ''double ou-tlet'' left ventriele. It is interest-Aiti thiat the genieral. shiape of the hear is,
niormiai in thiese. eases, for thiis means tiiat
eitiier tuec interruptioti of tlime fibroplastic coiitniuutmtii occurred after the. heart hiad acquired
mncost of' its shape., or thie fibrophastie eontini
uxitii is miwithier caue or(1 riesulit of the 1)cIid
In) tlue, prixutixe cardia,rc tube. -Also, tiiese
ea4seIS suggoest that thev limlite(l groxvtih capacityN
of thie fibroplastir, contin,11uum1 is iri part i.e
sl(Iishe f'or briningiito thie txwo ventricuilar-
''l'11(s(' cuibry ologile
II c
rings)ote xxeve ioliitoiar.x al resia ( sexerI
ol Neittelds5 (1s8(5 h11( Jplloiiirliiv ste1110515
lrg
1)111 iioie 1iaid pIlliioIlIarv altrlesa
i)llbatr sepilal df(let)' anld a xx'i(le 1)811(1 of 11111
ettllt
treejiaiit ingIlie toil till rin1g froiti I lie
ig tier
ouitflow reg,ionl. Neit her I le aloitie 1ii)
the Site o)f attachrlieiit ot iI lie amt r.et ie p)lMlil(
m, V.
o0/ itO
41/~ ~ ~ ~ ~NTI~ .TRA
impjlieationis
itifundihula togethier.
Thlere was onie heairt iiifthe present series
thlat closely resembledl tue hiearts described
1y Neufeld and ccoxvorkers amid J)crhlaps shieds
furthier Ight on this inaterestingp antomaly. Ift
is; siioxx'u In figntre 14, as vicxxed fr-oni thie
venitricula-r 11881. In adldition to resenblihig-
nlaux arlterx was evxli suggvest ivelv coiitiliiitois
xxiilte turid ring'. '['ile iiittssci]atiire sepflow
reami ltvd to
aratinig iiflox.1(
Ihe c(litirelx blhtllal. Inlseulta ire cotirsitig('I
etiiiitcreiiti.tllx armltld thle base of the( txx 0)
olutftlox '-I rite'l res'. Inl thlis ease, thenl. t.he separation oIf iittlox 81(1itt
oflow regonIMs flinl( the
of
the tiihrous cmotit 111111110-AWa
ititerritpt iou
aeemoqfc)II IIslIIe d Iv1)x hItIlhar1 iitseI II at I Ire1 . T'I I1
ilnflldibllolltllo. o)f tIhe roligt x i iem1( lotngli
JILxt.apose(1 the iii lldii(lltllmu of, the left x eti
tricele hut protrtudedl hex 01mi1 the v ciiiritular
ilase. Ihlie protrtusimll of the IIuLIIIl perhaps
cixplaitils wihy, -ill N'eufelds eae tile 1)111
and ort ie rings apjpear dooial
111.0111cMI
i(o he, .1ii the satne plcate wxitli eaeli othe.r, blitt
abno-rmtally distan-it from tile plhtte of thle inflow oritiees' a criterion xxhielhi thev found
usefi111 ill the el iiiieal reeoglnitill of, these
It is imossible that th ef(let ortit 'x ill t--ins
hear11.t is onlyv (ifferellt, ili (legree fro-ml t hat
1 l1s. s
(4in eertaitil othe(r heart-swti
N
i
notd
tioii. For example, -it xxvas piit
ouit that
(Ifften ill traiisposit 1011 the left x nuelrotittloxx orifice lies cOulisiderably i)eyoll( ~its n1or.
mia] position xxvith refer-nce to the ineiiiraiiace,ons sepItun., anid aii exampijle wxas slioxxvi in1
figure11 8. Aiid pr].otrtlsi(1 1 o the( hbUr1(011
poient heyo(111( the, hoty o)t thle left x ciii ricde
xxas inirticul:irly strikingT In t1w c'ase )f tr
i figure ii. (oIl ItI
A III
('tisp.,)I d a trecsia shown.
he that the factor a:ce.oulltilo- fo(.r this, protrIii
siin iin traiish)sfit ion wxheni more proIlullled(.
(lixvides the ti) )ilcmcoit iutitin and IlIn
righit xT c1Iit r i(de restll'ts
dotd)[le (titiet
Clearly there is iiin elit' tlo he learlied about
the iuor1Phogeiie1)(sis- (If CMiigeiiital card liai
tnomalies.
tinr,latimt,(
Vootw
tAttx xV'I
Norfttbcr
I
TRANSPOSITION OF GREAT VESSELS
Summary and Conclusions
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From earlier studies of the embryology of
the ventricular skeleton a new explanation of
the morphogenesis of transposition of the
great vessels is offered. It is simpler than
earlier torsion-detorsion theories, and provides criteria for differentiating tranlsposition
from other conotruncal anomalies, which previous theories do not. The theorv postulates
that there is, in effect, a shift in the orientation of the fibroplastic continuum which lines
the primitive heart tube, extending from the
A-V canal to the truncns arteriosus. Norinally this continuum holds the aortic part
of the truncus in fibrous continuity with the
mitral part of the A-V canal. It is suggested
that in transposition it is the pulmonic part
of the truncus that is held in continuity with
the mitral ring.
Such a morphogenetic sequence would be
accompanied by predictable abnormalities of
other parts of the ventricular architecture.
These would include (1) narrowing of the
crista supraventricularis., (2) re-orientation
of the bulbar part of the right ventricular
septal surface, (3) a particular lie of the coronarv ostia, and (4) certain deformities of
left ventricular musculature. Seventeen hearts
writh transposition and a number of control
hearts and hearts with other types of congenital conotruncal anomalies were studied.
In all iiistances the deformities predicted
were found to be present.
The abnormality of left ventricular museulature proved to be of special interest. It
is probable that the ventricular septal defect
which often accompanies transposition is, in
many instances, due primarily to an abnormalitv in the development of left ventricular
nmuscle. This is in contrast with the septal
defect seen in tetralogy of Fallot and other
conditions without transposition, where the
elaboration of bulbar nmusculature appears to
b)e primarilv at fault.
Regardinog the electrocardiogram in transposition, nearlv all cases niot coinplicated by
inflowNT tract deformities showed the 8152S3
pattern with QRS interval prolongation. This
Circulation, Volume XXVI, November
1962
839
pattern has in the past been attributed to
bypertrophy of the crista supraventricularis.
But in transposition the crista supraventricularis is always greatly reduced in mass and
surface area. To resolve this paradox withinl
present electrocardiographic theory, it is suggested that the mean QRS vector in tranisposition may be a resultant of two other simultaneously generated vectors. One is fromn the
left ventricle, showing left axis deviationi
secondary to the left ventricular musenlar
abnormality of transposition; the other is
from the hypertrophied, dilated right ventriele and shows marked right axis deviatiotn,
The resultant of two such vectors would write
the S1S2S3 pattern.
The anatomic differentiatioin of tranisposition from certain other outflow tract anomalies is discussed. In particular the ventricular
skeletal abnormalities are compared in (1)
conventional bulbar septal defect with mnarked
overriding" by the aorta, (2) persistenice
of the trunieus arteriosus, (3) "pseudotruncus," anid (4) the svndrome of the "double
outlet" right ventricle.
Acknowledgment
The author wvishes to express his great indebtedness
to Prof. Jules Linzbach, Chief of the Pathology
Institute of the University of Goettingen in Western
Germany, for generously making the material and
resources of his Institute available, for his unflagging interest in this work, for his stimulating and
challenging ideas, and for his warm hospitality
during the author 's stay in Goettingen.
References
1. GRANT, R. P.: The embryology of the ventriicalar flow pathways in man. Circulation 25:
756, 1962.
2. GOERTTLER, K.: Hemodynamische Untersuchungen
fiber die Entstehung von Missbildungen des
arteriellen Herzendes. Virchow 's Arch. 328:
391, 1956.
3. DE VRIES, P. A., AND SAUNDERS, J. D. M.:
Developmenit of the ventricles and spiral outflowv tract in the human heart. Contribution
to Embryology No. 256, Carnegie Institute
of Washington. Baltimore, 1961.
4. SPITZER, A.: tber dein Bauplan des missgebildeten Herzens. Virchow 's Arch. 243: 81, 1923.
5. HARRIS, J. S., AND FARBER, S.: Transposition
of the great vessels. Arch. Path. 28: 427, 1939.
GRANT
840
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6. BARTHEL, H.: Missbildungen des menschlichen
Herzens. Stuttgart, Georg Thieme, 1960.
7. GOuL-D. S. E.: Pathology of the Heart. Springfield, Illinois, Charles C Thomas, 1960.
8. HARDIN, G.: Nature ad(l mani's fate. Newv York,
Rhinehart, 1959.
9. PERN.KOPF, E., AND WIRTINGER, W.: Das Wesen
der Traiisposition im Gebiete des Herzens.
Virehowx 's Arch. 295: 143, 1935.
10. LEV, M'., AND SAPHIR, 0.: Transposition of the
great vessels. Arch. Path. 39: 172, 1945.
1 1. DE LA CREZ, M. V., AND DA ROCHA, J. P.:
An ontogenetie tlheory for the explanation
of congeniital aiialformations insvolvinig the
truineus and eonus. Amii. Heart J. 51: 782, 1956.
12. SHANER, R. P.: Complete anid corrected transposition of the aorta, pulmiionary artery, aind
ventricles in pig embryos. Am. J. Anat. 88:
35, 1951.
13. DOERR, MT.: Die forinale Entstehuntg der wvichtigsten Missbildungen des a rteriellen Herzens.
Beitr. path. Anat. 115: 1, 1955.
14. GOERTTLER, K.: -Normiale unid patlhologische
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15. GOERTTLER, K.: Die Stoffwechseltopographie des
embryonalen Huhnherzens und ihre Bedeutung
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Verhandl. deutsch. path. Gessellseh. 40: 181,
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16. GROHMANN, D.: Mitotische Wachstunmsintensitit
dles emhbryonalen und fetalen Hiihnehenherzens.
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17. KRAMIER, T. C.: Partitioning of the truncus and
conus in the human hjeart. Aml. J. Anat. 71:
343, 1942.
18. GRANT, R. P.: Dextroversion. Circulation 18:
25, 1958.
19. GRANT, R. P., DOWNEY, P. M., AND MAMAHON,
H.: Architecture of the right ventricular
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20. GRANT, R. P.: Spatial vector electrocardiography.
New York City, Blakiston Division of McGraw
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2-1. NEUPELD, H. N., DUSHANTE J. W., AND
EDWARDS, J. E.: Origin of both great vessels
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Difference of Opinion
I cannot fall out or contemnn a man for an errour, or conceive why a differenee in
Opinion should divide an affection; for Controversies, Disputes, and Argumentations,
both in Philosophy and in Divinity, if they meet with discreet and peaceable natures, do
not infringe the Laws of Charity. In all disputes, so much as there is of passion, so
inuch there is of nothing to the purpose; for then Reason, like a bad Hound, spends
upon a false Scent, and forsakes the question first started. And this is one reason whv
Controversies are never deteramined; for, though they be amnply proposed, they are
scarce at all handled, they do so swell with unnecessary Digressions; and the Parenthesis
on the party is often as large as the main discourse upon the subject.-SIR THOMAS
BROWNE. Religio Medici. Edited by W. A. Greenhill, M.D. London, MacMillan and Co.,
Ltd.. 1950, P. 98.
Circulation, Volume XXVI, November 1962
The Morphogenesis of Transposition of the Great Vessels
ROBERT P. GRANT
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Circulation. 1962;26:819-840
doi: 10.1161/01.CIR.26.5.819
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
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