Download Developmental Changes in the Myocardial Architecture of the Chick

THE ANATOMICAL RECORD 248:421–432 (1997)
Developmental Changes in the Myocardial Architecture of the Chick
DAVID SEDMERA,1* TOMAS PEXIEDER,1 NORMAN HU,2 AND EDWARD B. CLARK2
1University of Lausanne, Institute of Histology and Embryology, Lausanne, Switzerland
2National Institutes of Health, Specialized Center of Research in Pediatric Cardiovascular
Diseases, Strong Children’s Research Center, Department of Pediatrics, University of
Rochester School of Medicine & Dentistry, Rochester, New York
ABSTRACT
Background: Numerous studies describing myocardial architecture have been performed on the adult heart but considerably fewer
have been made during embryonic or fetal development. To serve as a
basis for interspecies comparison of ventricular morphology, and as a
reference for studying the effects of experimental perturbations, we examined
the development of chick throughout the entire incubation period.
Methods: Chick hearts from stage 14 (day 2) to stage 46 (day 21) were
perfusion-fixed, and sectioned in transverse, frontal and sagittal planes.
The ventricular myocardial architecture was examined and photographed in the scanning electron microscope.
Results: At embryonic stage 16 and earlier, the smooth-walled heart loop
had an outer myocardial mantle, cardiac jelly, and endocardium. From
stage 18, there was an outer compact and inner trabeculated myocardium.
Trabeculated myocardium could be subdivided into the outer (basal)
portion adjacent to the compact layer and the central (luminal) part. The
outer basal layer could be distinguished from the inner luminal by shorter
and finer trabeculae with small, round intertrabecular spaces. From stage
24, the patterns of trabeculae and intertrabecular spaces were ventriclespecific. Between stages 24 to 31, abundant trabeculations were present
throughout both ventricular cavities. The trabeculae were initially radially arranged, but later adopted a spiral course, which persisted in a
simplified form into adulthood.
Conclusions: The ventricular myocardium undergoes distinctive morphogenesis, characterized by changes in trabecular patterning and orientation. We speculate that the embryonic trabecular architecture reflects the
directions of the main stresses. Unlike fetal and adult hearts, which rely
mostly on the compact myocardial layer, the trabeculae play a crucial role
in the contractile function of the embryonic heart. Anat. Rec. 248:421–432,
1997. r 1997 Wiley-Liss, Inc.
Key words: chick embryonic heart; trabecular pattern; perfusion-fixation; SEM; contractility
The developmental processes that transform the
primitive tubular heart, with its peristaltoid contractions, into the mature four-chambered heart of higher
vertebrates, have long since attracted the attention of
investigators (Vesling, 1664). Events during the embryonic period, when the ventricular myocardium has a
sponge-like appearance, thus resembling that of lower
vertebrates, have often been studied (Ben-Shachar et
al., 1985; Icardo and Fernandez-Teran, 1987). However,
substantially less is known about its transformation
into the mature form and no systematic study throughout prenatal development has been made.
The early phases of development of ventricular trabeculation in the chick embryo have been described by
Icardo and Fernandez-Teran (1987). They proposed
that the mechanism of trabecular formation involves
r 1997 WILEY-LISS, INC.
endocardial invasion disaggregating the initially compact myocardial mantle. However, this study neither
focused on the changes in trabecular pattern nor described the stages beyond day 5 (HH stage 27; Hamburger and Hamilton, 1951), after which many of these
changes occurred. Ben-Shachar et al. (1985) studied
chick hearts between HH stages 16–39 and described
the initial trabecular arrangement as radial. They
emphasized the importance of trabecular coalescence in
Contract grant sponsor: the Swiss National Science Foundation;
contract grant number: 31-38889.92; contract grant sponsor: NIH;
contract grant numbers: P50-HL51498 and HL-42151.
*Correspondence to: David Sedmera, Institute of Physiology, University of Lausanne, Rue du Bugnon 7, CH-1005 Lausanne, Switzerland.
E-mail: [email protected]
Received 9 October 1996; accepted 4 February 1997.
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D. SEDMERA ET AL.
ventricular septation and did not consider in detail the
fate or possible functions of the remaining trabeculae.
Wenink (1992) analyzed quantitatively the trabecular
patterns of early human hearts, and reported differences between the left and right ventricle, which change
during development. The role of trabeculation in propagation of excitation was demonstrated by de Jong et al.
(1992) who showed that they are responsible for rapid
propagation from central septal structures to the ventricular apexes, which is important for proper coordination of ventricular contraction. The later development
of right ventricular trabeculation (between incubation
days 6–14) was studied by Rychterova (1971). She
described the process of fusion of the basal portions of
the trabeculae in the right ventricle and demonstrated
their important contribution to the thickening of the
compact myocardium. The differences in trabecular
pattern between left and right avian ventricle are well
documented in both embryonic (Rychter and Rychterova, 1981; Ben-Shachar et al., 1985; Manasek et al.,
1986; Icardo and Fernandez-Teran, 1987) and adult
chick (Komarek et al., 1982; King and McLelland,
1984). The geometrical difference between the left and
right ventricle is one of the factors responsible for
cardiac failure in transposition of great arteries (Parrish et al., 1983; Castaneda et al., 1994). Important
differences between different heart regions also exist at
the molecular level (Zimmer, 1994; Barton et al., 1995).
The pattern of trabeculation is influenced by genetic
and epigenetic factors. Myocardial architecture has
been altered in RXR alpha knockout transgenic mice
(Sucov et al., 1994; Kastner et al., 1994). Abnormalities
of the ventricular myocardium in the retinoic acidtreated mouse embryos are an example of chemical
teratogenesis (Pexieder et al., 1992). Broekhuizen et al.
(1995) reported abnormal function of hearts in retinoic
acid-treated chick embryos, which might be related to
abnormalities in the myoarchitecture, such as thinning
of the compact myocardium (our unpublished observations). Haemodynamic forces affect heart morphogenesis, and abnormal myocardial architecture is produced
in the perturbated flow patterns (Rychter et al., 1979;
Rychter and Rychterova, 1981). These and other similar studies prompted us to reexamine in detail the
Abbreviations
Ao
AL
At
AV
Co
Ct
DL
En
IS
LA
LV
LVP
Mi
mp
My
Pu
RA
RV
RVP
RVS
SV
Tr
aorta
ascending loop
atrium
atrioventricular junction
compact layer of the ventricular wall
conotruncus
descending loop
endocardium
interventricular septum
left atrium
left ventricle
left ventricle, parietal view
mitral valve
papillary muscle
myocardium
pulmonary artery
right atrium
right ventricle
right ventricle, parietal view
right ventricle, septal view
sinus venosus
trabecula
Fig. 1. HH stage 14. a: Frontal view of looped tubular heart indicating level of section and face viewed (arrowheads) in the next figure.
b: Cross section shows the smooth inner relief and three-layered
structure of the wall (outside to inside): myocardial mantle (My),
cardiac jelly (star), and endocardium (En). Scale bar 5 100 µm.
normal development of myocardial architecture. The
aim of this study is to describe the course of normal
development of ventricular myocardial architecture in
the chick heart. These results will serve as a standard
(norm) for future experimental studies. They will also
provide a background for quantitative evaluation of
biomechanical parameters, necessary to be able to
develop a mathematical model of trabeculated heart.
MATERIALS AND METHODS
Fertilized White Leghorn chicken eggs were incubated in a forced-draft 37.5°C incubator with four
rotations per day from stage 14 (2 days) to stage 46 (21
days, hatching; Hamburger and Hamilton, 1951). We
studied stages 14 to 24 at an interval of 12 hours, stages
27 to 36 at an interval of 24 hours, and stages 39 to 46 at
an interval of 3 days. At least three hearts per stage
were examined.
CHICK VENTRICULAR TRABECULATION
423
Fig. 2. HH stage 18. a: In a frontal view, primitive atrium (At),
ventricle (V), and conotruncus (Ct) can be distinguished. b: Primary
trabeculae (Tr) in the apex are arranged as dorso-ventral ridges. The
compact layer (Co) is thin and remnants of cardiac jelly (star) are
present in the area of atrioventricular junction. c: The caudo-cranial
view of the successive slice shows the smooth inner wall of the atrium,
sinus venosus (SV), and conotruncus. Scale bar 5 100 µm.
A tapered glass cannula with diameter of 30 to 160
µm was inserted into the ventricle, and the hearts were
perfusion-fixed at high flow low pressure (Pexieder,
1981) with 2% glutaraldehyde-1% formaldehyde in
isotonic 0.1 M cacodylate buffer. Direct ventricular
perfusion washed out the blood and arrested the hearts
in end-diastole. The hearts were then postfixed in 1%
osmium tetroxide, and photographed in 3 standard
projections (frontal view, left and right profiles) under a
M400 photomacroscope (Wild, Heerbrugg, Switzerland). The specimens were cut transversely to the long
axis with thinned microdissection scissors into 0.15–
0.25 mm thick slices. Additional dissection in frontal
and sagittal planes was also performed. The slices were
ethanol-dehydrated, and critical point dried using freons in a CPD 030 critical point dryer (Balzers, Liechtenstein). After mounting on stubs with colloidal silver, the
specimens were coated with 300 nm of gold in a S150
sputter coater (Edwards, Zivy, Basel, Switzerland), and
photographed in a JSM 630OF scanning electron microscope (JEOL, Tokyo, Japan).
mantle of myocardium with a basal membrane, an
acellular extracellular matrix (cardiac jelly), and a
single cell layer thick endocardium (Fig. 1). Although
the inner relief was smooth, the endocardium contained
numerous fenestrations. The first signs of trabeculation could be found at stage 16 as oval pits in the inner
surface of the apical part of the cardiac loop (future left
ventricle). At stage 17, a pattern of distinct dorsoventrally aligned ridges or projections was apparent in the
ventricular apex. The ellipsoidal spaces among these
projections (lacunae) started to be enclosed at stage 18
(Fig. 2). This was the first occurrence of trabecular
branching into the lumen, and the ventricular wall
started to have a sponge-like appearance. The arrangement of the primitive trabeculation, which was the first
morphological sign of ventricular differentiation, is
schematically depicted in Figure 3. The cardiac jelly
disappeared during this process in areas other than
developing cardiac cushions. The trabeculation progressed in an apicobasal direction. The wall of conotruncus always remained smooth.
From stage 21 onwards, the trabecular pattern specific to the future right ventricle was distinguished in
the right lateral wall (Fig. 4). However, the interventricular septum was still morphologically undemar-
RESULTS
At stage 14, the heart was a smooth-walled, looped
tube composed of three layers: a thin compact outer
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D. SEDMERA ET AL.
Fig. 3. Schematic representation of primary trabeculation shows
that the process is limited to the primitive ventricle (V), while the
inner relief of the primitive atrium (At) and conotruncus (Ct) is
smooth.
cated. Trabeculation continued to increase, and by
stage 24, a fine trabecular network occupied almost
entirely both ventricular cavities. The trabeculae or
more precisely trabecular sheets by this stage were
oriented perpendicular to the outer compact layer in
the frontal plane. In transverse sections, they curved
parallel to the lateral wall or the interventricular
septum, which was well distinguishable by stage 24.
The trabeculated myocardium showed regional differences between its central and peripheral portion. The
trabeculae close to the compact layer were fine, short,
and oriented perpendicular to it. The intertrabecular
spaces were small and round, and their pattern was
similar in both right and left ventricle. The trabeculae
in the central (luminal) area were thicker, and the
intertrabecular spaces were oblong in shape and considerably larger than in the basal area. Trabeculae-free
lumina existed only in the basal parts of the ventricles.
The compact layer, relatively thin at these stages, was
bounded by the outermost extent of the endocardium.
The left and right ventricles were distinguishable by
their trabeculation patterns (Fig. 5). In the left ventricle, the central (luminal) trabeculae were thicker
than in the right ventricle, and were interconnected
only in the apical part. In the right ventricle, the
luminal trabeculae were shorter due to the high num-
ber of interconnecting segments, and radiated from the
interventricular septum in a fan-like pattern. The
intertrabecular spaces were considerably smaller than
those of the left ventricle, and their shape was less
oblong. This trabecular arrangement (Fig. 6) did not
change qualitatively until stage 29.
From stage 31 (day 7) onward, the trabeculae started
to change to long, thick bundles (trabeculae carneae)
that attached to the ventricular wall by their ends and
along the entire length (Fig. 7). The extent of tertiary
trabeculation was confined to the ventricular walls, and
trabeculae-free lumina were present in both ventricles.
The pattern of trabeculation was ventricle-specific. In
the left ventricle, the preferential orientation of the
trabeculae changed to longitudinal from the apex to the
mitral orifice, with some oblique connecting segments
between the main trabecular bundles (Fig. 8). In the
right ventricle, the trabeculae thickened as well, and
their radial arrangement started to spiral from HH
stage 36 (day 10). Fine trabeculations (trabeculae
tendineae) were observed in the apices of both ventricles (Figs. 8, 9, 10). Both sides of the interventricular
septum and the outflow tract of the left ventricle were
smooth. The thickness of the compact myocardium was
gradually increasing. From stage 34, subepicardial
sinusoids forming the coronary vascular bed were present.
By stage 39, the radial arrangement of the trabeculae
in the right ventricle became clearly spiral., with the
origin on the upper part of the muscular interventricular septum turning basally in a counterclockwise direction (Fig. 8). The thickness of trabeculae increased in a
basopical direction, but they were generally finer than
in the left ventricle. There were still numerous connecting segments between the main bundles. In the left
ventricle, similar spiralling of longitudinal apicobasal
ridges was also observed (Fig. 9). By stage 42, the heart
had further increased in size and the ventricles expanded considerably. However, there was no substantial change in the pattern of trabeculation, and the
spiral systems were distinctly present in both ventricles. The compact myocardium formed most of the
ventricular mass by that time. During further development, the interconnecting segments became much less
abundant, which gave the trabeculae a coarser, ropelike appearance (Fig. 10). The fine trabeculation in the
basal region of the right ventricle could be found even in
the most advanced stages studied. Both the right and
left sides of the interventricular septum adjacent to the
atrioventricular valves were smooth. By this time, the
trabecular pattern, schematically depicted in Figure
11, was essentially the same as in the adult chick.
DISCUSSION
The onset of ventricular trabeculation has been described in detail by Icardo and Fernandez-Teran (1987),
and our observations of the early trabecular pattern on
the organ level correspond well with theirs. As a
mechanism setting off trabeculation, they have suggested endocardial invasion into the cardiac jelly and
myocardium. The further development of trabeculation
is effected by apposition from the periphery, where
mitotic activity is highest (Rychterova, 1971; Tokuyasu,
1990). This was confirmed by DNA-labelling studies of
Thompson et al. (1995), who demonstrated that the
CHICK VENTRICULAR TRABECULATION
425
Fig. 4. HH stage 21. a: A frontal view shows still undivided ventricle
(V), atrium (At), and conotruncus (Ct). b: Inside, there is a fine
three-dimensional network of secondary trabeculation, which is starting to occupy the lumen. Compact (Co) and trabeculated myocardium
can be distinguished on the cross-section. Trabeculae (Tr) (arrow-
heads) do not yet fill the entire ventricular cavity. There is left to right
gradient in trabecular thickness. c: In the cranial slice, the trabeculae
of the lateral wall, which is about to belong to the right ventricle, have
predominantly radial arrangement. Stars, atrioventricular cushions.
Scale bar 5 100 µm.
myocytes in trabeculae are mitotically quiescent in
comparison with the compact layer, and by retroviral
lineage tracing studies (Mikawa et al., 1992), which
showed that the inner trabeculated layer grows at
slower rate than the outer compact myocardium in the
second half of incubation. The development of ventricular trabeculation progresses through three stages that
are similar to human or mouse embryos (Vuillemin and
Pexieder, 1989; Jouk and Pexieder, unpublished data;
Si Minh Pham, personal communication). The Type I
(primary) trabeculation is characterized as trabeculae
attached full length to the ventricular wall. BenShachar et al. (1985) described the orientation of the
primitive trabeculation as radial, which corresponds
well with our results and the initial stages of apical
trabeculation in mammalian heart (Vuillemin and Pexieder, 1989).
Type II (secondary) trabeculation can be found at
stages 21 to 31. This consists of fine trabeculae with
abundant branching, filling almost the entire ventricles. The cranial portion of the trabeculation marks
the proximal boundary of the conotruncus, which has a
smooth inner relief (Pexieder, 1978). In mammalian
heart, the trabeculae show more pronounced regional
differences in thickness between their basal and lumi-
nal parts. In mouse hearts prepared for SEM, they
appear generally coarser than in the chick. Unlike in
human or mouse embryos (Wenink and Gittenberger-De
Groot, 1982; Vuillemin and Pexieder, 1989; Jouk and
Pexieder, unpublished data, 1997; Si Minh Pham, personal communication), the arrangement of the secondary trabeculae in the chick is not uniform (isotropic),
but shows a distinct pattern of orientation. This orientation is dorsoventral in the left ventricle, but radial in
the right (Ben-Shachar et al., 1985; Icardo and Fernandez-Teran, 1987). Secondary trabeculation in the mouse
seems to be more symmetric than in the chick. This
could be due to different spatial arrangement and
geometry of the embryonic mouse heart. The ventricular chambers in mouse are two ellipsoids communicating through the interventricular foramen, rather than a
cylinder with a cone wrapped around it as seen in chick.
An ellipsoid has more planes of symmetry than a cone.
These differences are mostly marked in the embryonic
period. The fetal chick and mouse hearts are more
similar to one another. Wenink (1992) studied quantitatively the right and left trabecular patterns on histological series of CRL 4.0–42 mm human embryos. Initially,
the trabeculae were thicker in the left ventricle, but
after CRL 25 mm they became thicker in the right
426
D. SEDMERA ET AL.
Fig. 5. Dissection of HH stage 27 heart. a: All four chambers are
externally demarcated on the frontal view. b: In the apex, the number
of interconnecting segments is high, and interventricular septum
starts to form by coalescence of the trabeculae (arrows). c: Left and
right ventricle are easily distinguishable by different trabeculation
patterns. Note the fine secondary trabeculation, filling most of both
ventricles. d: Trabeculae-free lumen exists only in the basal portions of
the ventricles, separated by fine interventricular septum (IS). The
walls are still heavily trabeculated. e: Trabeculation limits the proximal extent of septating conotruncus (Ct), which is smooth. Scale bar 5
100 µm.
ventricle. The discrepancy with our data might reflect
the differences between classes, and also the importance of trabecular remodeling in the fetal period. In
this respect the human heart, being mammalian, is
more similar to that of mouse, which should be kept in
mind when attempting to model the human heart
biomechanically.
There are also important regional differences within
trabeculated myocardium. The basal trabeculae adjacent to the compact layer are finer, and their orientation is perpendicular to it in both ventricles. The
corresponding intertrabecular spaces are small and
round. During the course of development, this layer
gradually regresses in a basoapical direction, as its
putative nutritive function is taken over by developing
coronary circulation (Rychterova, 1971; Rychter and
Ostadal, 1971). The process of compaction of the basal
portions of the trabeculae contributes to the increase of
thickness of the compact myocardium (Rychterova,
1971). Coronary vascularization starts to develop at
stage 34 (day 8) and is completed at stage 40 (day 14)
(Rychter and Rychterova, 1981; Waldo et al., 1990). We
believe that the secondary trabeculation is a temporary
CHICK VENTRICULAR TRABECULATION
Fig. 6. A schematic representation of the secondary ventricular
trabeculation pattern at its maximal development (approximately HH
stage 28) on transverse and frontal sections.
compromise between the need to increase myocardial
mass so as to cope with the elevated functional requirements (Clark et al., 1986), and a lack of adequate blood
supply (Tokuyasu, 1990).
If the only function of all the intertrabecular spaces
was to provide nutrition (Minot, 1901), one would
expect them to be a spherical shape with an isotropic
arrangement. In contrast, the radial arrangement of
secondary trabeculation and the ellipsoidal shape of the
intertrabecular spaces probably reflects the direction of
stresses during contractions by analogy with the orientation of collagen fibrils in the aortic valve leaflets, i.e.,
perpendicular to the wall tangent at any point (Peskin
and McQueen, 1994). Together with Wenink et al.
(1996) we speculate that the trabeculae are the main
contractile element at these stages. The arrangement of
secondary trabeculation supports its role in ventricular
contractility. It should also be noted that the cells in
trabeculae form most of the myocardial mass during
this period (Sedmera et al., 1995), and are more differentiated than the cells in the compact layer (Markwald,
1969; Thompson et al., 1995; Wenink et al., 1996).
The relatively high proportion of trabeculae in embryonic hearts resembles the situation found in fishes and
427
amphibians. The ventricular compartments of lower
vertebrates are extensively trabeculated, and have only
a thin compact layer (Van Mierop and Kutsche, 1984).
All these hearts generate relatively low pressures, and
are supplied by not completely oxygenated blood, so
this arrangement might be important for nutrition and
oxygenation of the working myocardium. The dorsoventrally aligned, sickle-like folds observed in chick embryonic left ventricle may serve the same purpose (blood
compartmentalization; Hogers et al., 1995) as those seen
in the non-septated hearts of lower vertebrates such as
frog. They also form the muscular part of the interventricular septum (Ben-Shachar et al., 1985). As shown by
de Jong et al. (1992), they are also an important
element of ventricular conduction at stages 23–31.
Type III (tertiary) trabeculation starts from stage 31
(day 7) onward, and these trabeculae are long, thick
bundles attached to the wall by their ends and along
their entire length. The only previous study concerning
this period was that of Rychterova (1971), who described the fate of right ventricular trabeculation between incubation days 6 (stage 29) and 14 (stage 40),
but in less detail than the current study. The extent of
tertiary trabeculation is limited mainly to the walls, so
free lumen is present in both ventricles by this time.
The pattern of tertiary trabeculation is again ventriclespecific. In the left ventricle, it is composed of longitudinal, slightly spiraled ridges (trabeculae carneae),
stretched between the apex and the mitral orifice,
where they end as papillary muscles. There are also
oblique connecting segments between them. Both sides
of the interventricular septum, together with the outflow tract of the left ventricle, are smooth. This arrangement could serve several functions. They provide support for the mitral valve leaflets and enable better
apposition of the inner wall in systole (similar to the
slits and scallops in the mitral valve: Solomon and
Nayak, 1994). They might also participate directly in
the contractile function of the left ventricle, since the
direction of trabeculae is the same as that of the muscle
fibres in the compact layer (Jouk et al., 95). The tertiary
trabeculae are also associated with the terminal
branches of the conduction system (Anderson and
Becker, 1980), thus providing the morphological substrate for coordinated contraction of the left ventricle.
Fine trabeculations (trabeculae tendineae), found in
the ventricular apexes, are composed purely of the
conduction tissue. The pattern of trabeculae in the
right ventricle is more complicated. Their contribution
to total myocardial mass is more substantial than in the
left ventricle. They are arranged in an anticlockwise
spiral, which begins at the cranial end of muscular
interventricular septum and runs first to the apex and
then towards the conotruncus. This spiral course again
resembles the arrangement of muscle fibres in adult
(Streeter, 1979) or fetal (Jouk et al., 1995) heart, and
the bellows-like pattern of trabeculae is probably important for the contractility (Castaneda et al., 1994).
Another possible function is the strengthening of the
comparatively thinner ventricular wall. Similarly, as in
the human fetuses (Jouk and Pexieder, unpublished
data), the pattern of tertiary trabeculation can be
directly matched with the adult one. On the other hand,
mouse embryos close to term show much more abundant trabeculations (Vuillemin and Pexieder, 1989; Si
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D. SEDMERA ET AL.
Fig. 7. HH stage 31. a: Frontal view showing nearly adult external
morphology, with all chambers demarcated. b: In the apical part of the
left ventricle, the trabecular arrangement is becoming apico-basal.
The apical part of the right ventricle contains small, rounded intertrabecular spaces. c: In the left ventricle, the extent of trabeculation
starts to be limited to the lateral wall. The muscular interventricular
septum, apparently belonging mostly to the left ventricle, can also be
seen. d: The area of trabeculae-free lumen increased. In the LV, the
compact layer forms most of the myocardium, and the papillary
muscles (mp) can be seen in cross section. The trabeculae still form a
significant proportion of the right ventricular (RV) wall. The muscular
interventricular septum by this stage. e: The last slice shows the
inflow and outflow tracts of both ventricles. Scale bar 5 100 µm.
Minh Pham, personal communication), which corresponds with their less advanced development at birth
compared to chick.
The differences of trabecular arrangement can be
attributed to different left/right ventricular geometry (a
prolate ellipsoid rather than a cone, or more precisely a
crescent), and the contraction pattern (circular rather
than bellows-like) (Hutchins et al., 1978; Castaneda et
al., 1994). The left ventricle is proportionally larger in
adult birds than in mammals probably because a
greater blood supply is needed for the powerful flight
muscles (Komarek et al., 1982; King and McLelland,
1984). The avian left ventricular compact layer is about
five times thicker than the right one, while in mammals
this ratio is about 3:1. The proportion of trabeculae in
the right ventricle is higher than in the left one, which
relies mostly on its compact layer. The maturation of
the right ventricle is characterized by the gradual
CHICK VENTRICULAR TRABECULATION
429
Fig. 8. HH stage 39. a: Frontal view indicating cuts and directions of
observation (arrowheads). b–d: Sagittal dissection of the heart. In the
parietal part of the right ventricle (RVP), the trabeculae have a spiral
course and numerous cross bridges. In the septal part (RVS), the
origin of the trabecular radiation at the end of muscular interventricular septum can be seen. Star indicates the pulmonary trunk. In the
parietal part of the left ventricle (LVP), trabeculae can be observed in
a longitudinal pattern, merging with the papillary muscles. Trabeculae tendineae, formed by conduction tissue, can be found in the apical
part (arrow in d). IS, part of the interventricular septum with a bit of
the right ventricle (RV). Scale bar 5 1 mm.
430
D. SEDMERA ET AL.
Fig. 9. HH stage 42. a: In the apex of the left ventricle can be seen the origin of major spiraled bundles of
tertiary trabeculation, which end as papillary muscles. b: The section at the midportion level shows the
limited extent of tertiary trabeculation in the left ventricle (LV) and the spiral system in the apex of the
right (RV). Scale bar 5 1 mm.
Fig. 10. HH stage 45, frontal dissection. The heart increased in size,
mainly in longitudinal axis. Both dorsal (a) and ventral (b) halves of
the heart are shown, which gives an idea about three-dimensional
organization of trabeculation, very similar to the adult pattern.
Apicobasal counterclockwise spiral systems can be recognized in both
ventricles. Arrow, interatrial septum; star, right AV valve. Scale bar 5
1 mm.
431
CHICK VENTRICULAR TRABECULATION
In this study, we have presented a qualitative morphological description of the development of the chick
ventricular trabeculation. This method and data serve
as the basis for interspecies comparisons of ventricular
morphology and as a reference for studying the effects
of experimental modifications such as conotruncal banding, drug treatment, or genetic manipulations.
ACKNOWLEDGMENTS
Our thanks are due to Mrs. Ariane Gerber for excellent technical help, Dr. Penny Thomas (National Heart
and Lung Institute, London, UK) and Dr. Bradley B.
Keller (University of Rochester, Rochester, NY) for
challenging discussions and kind revision of the manuscript. We also appreciate inspiring discussions with
Dr. Si Minh Pham, who made available to us his
unpublished data concerning normal development of
mouse ventricular trabeculation. This work was supported by Swiss National Science Foundation grant
31-38889.92 (T.P.), and NIH grants P50-HL51498 and
HL-42151 (E.B.C., N.H.).
LITERATURE CITED
Fig. 11. Schematic representation of tertiary trabecular pattern. In
the left ventricle, only two of the principal bundles are shown for
clarity. In both ventricles, the trabeculae can be followed in a
counterclockwise apicobasal spiral (when viewed from base towards
the apex), so the right-left differences can be mainly attributed to
different ventricular geometry (cone/crescent vs. cylinder/prolate ellipsoid).
thickening of existing trabeculae, the spiralling of their
courses, and the reduction in their number (Rychterova, 1971). We believe that the remaining trabeculae
serve as a support against excessive expansion since
the compact layer of the ventricular wall is quite thin.
In summary, when viewed from the base towards the
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