Paper - The first contractions of the heart in rat embryos

From Embryology
Revision as of 13:33, 1 May 2018 by Z8600021 (talk | contribs)
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)
Embryology - 13 Apr 2024    Facebook link Pinterest link Twitter link  Expand to Translate  
Google Translate - select your language from the list shown below (this will open a new external page)

العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)

Goss CM. The first contractions of the heart in rat embryos. (1938) Anat. Rec. 70: 505.

Online Editor  
Mark Hill.jpg
This historic 1938 paper by Goss describes early development of heart contraction in the rat embryo.

Modern Notes: heart | rat

Cardiovascular Links: cardiovascular | Heart Tutorial | Lecture - Early Vascular | Lecture - Heart | Movies | 2016 Cardiac Review | heart | coronary circulation | heart valve | heart rate | Circulation | blood | blood vessel | blood vessel histology | heart histology | Lymphatic | ductus venosus | spleen | Stage 22 | cardiovascular abnormalities | OMIM | 2012 ECHO Meeting | Category:Cardiovascular
Historic Embryology - Cardiovascular 
1902 Vena cava inferior | 1905 Brain Blood Vessels | 1909 Cervical Veins | 1909 Dorsal aorta and umbilical veins | 1912 Heart | 1912 Human Heart | 1914 Earliest Blood-Vessels | 1915 Congenital Cardiac Disease | 1915 Dura Venous Sinuses | 1916 Blood cell origin | 1916 Pars Membranacea Septi | 1919 Lower Limb Arteries | 1921 Human Brain Vascular | 1921 Spleen | 1922 Aortic-Arch System | 1922 Pig Forelimb Arteries | 1922 Chicken Pulmonary | 1923 Head Subcutaneous Plexus | 1923 Ductus Venosus | 1925 Venous Development | 1927 Stage 11 Heart | 1928 Heart Blood Flow | 1935 Aorta | 1935 Venous valves | 1938 Pars Membranacea Septi | 1938 Foramen Ovale | 1939 Atrio-Ventricular Valves | 1940 Vena cava inferior | 1940 Early Hematopoiesis | 1941 Blood Formation | 1942 Truncus and Conus Partitioning | Ziegler Heart Models | 1951 Heart Movie | 1954 Week 9 Heart | 1957 Cranial venous system | 1959 Brain Arterial Anastomoses | Historic Embryology Papers | 2012 ECHO Meeting | 2016 Cardiac Review | Historic Disclaimer

Rat Links: rat | Rat Stages | Rat Timeline | Category:Rat
Historic Embryology - Rat 
1915 Normal Albino Rat | 1915 Abnormal Albino Rat | 1915 Albino Rat Development | 1921 Somitogenesis | 1925 Neural Folds and Cranial Ganglia | 1933 Vaginal smear | 1938 Heart
Historic Disclaimer - information about historic embryology pages 
Mark Hill.jpg
Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

The First Contractions of the Heart in Rat Embryos

C. M. GOSS 1')€per'tmen.t of A.-nrnfomy, College of Pk-jj8fC’t-(.!»'nS and S-irrgeoi-i..s, (,.‘o.iI-2.;-mhic {.2-‘=3-i.—1E1,-'e9'.s'*'i‘£3;



The earliest contractions of the embryonic hearts which will be described in this communication, were obseiyed in hanging drop cultures of Whole rat embryos.

The initiation of contraction has been observed in two other forms, namely, in the chick by Patton and Kramer (’33), Sabin. (’20) and Johnstone (’2i' ) and in Amhlystoma by lopesnhaver ’3T ). According to these authors, the first portion of the heart which becomes active is the ventricle, and the myocardium contracts vigorously for some tim-e before circulation of the blood is established. The development of function in the rat will be seen to follow the same general pla11. Certain differences, however, correlated with differences in the morphological development will be described. A comparison of the structure of the rat heart with that of other mammals at the same stage of development suggests that the type of functional activity observed in the rat may be characteristic of mammalian embryos. In order to facilitate the study of the morphology of the heart and associated structures at the stage of beginning contraction, a Wax plate reconstruction Was prepared of a rat embryo of corresponding age fixed in the uterus.

Material and Methods

The technique for removal of rat embryos and their preparation in hanging drop tissue cultures has been described by Nicholas and Rudnick C34) and a few modifications are given by Gross (’35). The medium which gave the most fayorable results was composed of 1 part chicken plasma and 4 parts extract of newborn rat hearts in a buffered salt (Tyrode) solution.

The age of the embryos at the time of initiation of contraction was estimated at approximately days. It is not possible to make an exact determination of the age in days and hours for two reasons. First, Variations in the stage of development of embryos in the same litter frequently correspond to as much as 4 to 6 hours of normal development. That is, in the same litter embryos are obtained which have no recognizable heart primordium along with embryos in which the heart has developed into a saceular organ that is contracting vigorously. Second, a similar or greatersvariation in stage of development is found between embryos of different litters although they are of the same age as calculated from the time of copulation. The most accurate designation of age that can be gsiyen as a result of these experiments is 9 days and 14 5; hours. i

The following procedure, Worked out by experience, has been found useful to obtain embryos of the desired age Without resorting to the tedious method of observing the copulation time. As a routine, the oestrous cycles of the female rats in the colony were determined by vaginal smear between the hours of 9 and 11 in the morning. "When a female was found tobe in proestrum or ‘stage one’ (of Long and Evans, ’22), she was placed in a cage with a male. If sperm was recovered in the vagin a1 smear next morning, it was assumed that copulation had taken place during the early morning hours. (According to Long; and Evans, stage one lasts 12 hours and mating takes place in the early hours of stage two). The majority of embryos in a litter removed from the uterus after noon of the tenth day were, in most cases, in the desired stage of development. Embryos obtained before noon were usually too young and those removed after 4 o’cloek, too old.

Stage of Development

The developmental age of the embryos can best be determined by a description of the embryo at the time of beginning heart activity. The embryonic vesicle or blastocyst is approximately 2 mm. in length. It corresponds in most respects to stage 16 of Nicholas. Figure 8 is a sketch of a living embryo immediately after removal from the uterus.

Fig.1 Wax plate reconstruction of cephalic portion of 9-day 15-hour rat embryo fixed in utero. Viewed from ventral surface. X 400 reduced to X" 100.

The medullary folds and the foregut. invagination are the most conspicuous structures. The cephalic portion of the neural folds forms a prominent forebrain which extends cephalad beyond all other portions of the embryo. The neural groove is deep in the cephalic region but gradually becomes shallower until there is merely a medullary plate at the caudal end of the embryo. The allantois is a. blunt projection which lies outside of the amnion, extending into the cavity of the yolk save. The number of somites varies from 2 to 4. The embryo in figure 1 had 3 somites, that in figure 8 also had 3. The number of somites was found to correspond less closely to the stage of development of the heart and nervous system than the latter did to each other. The wall of the yolk sac contains both solid primitive blood islands and those with endothelial lined cavities and free blood cells, but the latter have not yet taken on the yellow color of hemoglobin. The perieairdisal ciatvixy is shaped like the letter U. The ciirved portion lies close zigaiiiist the lip of the anterior intestinal portal. The arms extend back to the region of the somites wliere the perioardial eavi.ty is connected with the extra enibryonie coelom. The heart and its associated Si,I'11C-‘E-l1I‘CS' will require a more detailed description.

Fig.2 Same reconstruction as in figure 1 with most of entoderm removed.

Description of the Heart

The difficulty of following the delicate endothelial structures in the living embryo was so great that a wax plate reconstruction was ‘[)1"Q'f)E1.I'@d of an emlirjro fixed in the uterus. This particular embryo was selected froma number of fixed specimens because it most closely resembled the lllfillg embryos in development. Figiires 1 to 5 are d1"ELWi1]g‘S of the reconstruction.

The endoeardium consists of two parts, the lateral pi:-i~ rnordia which are endotlielial tubes and a median portion which has no lumen. Both parts are combined into a continuous network or sheet of cells (fig. 2) which €VG:1‘y'Wl].B1”'8 in Contact with splanehliic. mesoderm. In the median portion, small scattered Vesicles (fig. 2) 1’*IE_‘p1"eS€11iZ the earliest development of a lumen. In this condition the tissue is more accu—rately termed a primordium of endocardium than primitive endocardium. It is the angioblast of many authors. Except for the scattered Vesicles, the median portion is a lamina composed of a single layer of flattened cells. It is definitely separated from the entoderm througliont and from the splanchnic mesoderm except at its cephalic border. Strands of cells from the lamina pass around the foregut on both sides to become continuous with the primitive dorsal aortae. They are the primordia of the first aortic arch-es and that portion of the lamina which lies between them will be incorporatedtinto the aortic sac (figs. 2, 3 and 4). The aortae are endothelial tubes, patent from the arch primordia to the region caudal to the somites. They are continued into the cephalic mesenchyme as the primitive carotid arteries (fig. 5).

Fig. 3 Same as figure 2 with windows cut through endocardinm and pericardial mesoderm in order to show internal structures.

Fig. 4 Same reconstruction as in figure 3. The cephalic portion of the neural folds and the pericardial mcsoderm have been removed. Viewed 3’:'ron1 the cephalic end.

The endothelial tubes of the lateral heart primordia cross the lateral plates of splanchnic mesoderm diagonally. They form a shallow are with its convexity away from the midline. At the outer edges of the lateral cardiac plates, the tubes merge with the primordia of the veins whichmay contain scattered vesicles but do not have a continuous lumen. A short distance from this junction with the veins, the lumen of each tube is constricted by an inward projection of endo cardium which resembles an imperfect valve. This constric~ tion is remarkably constant in its form and location. It marks the separation of the future atrium and ven.tr_icle, often called the atrioventricvular canal, but at this stage it is a sharp constriction rather than a canal. It is the most important landmark. for determining the area in which to observe the heart for its first contractions. The portion of the tube between the veins and the corrstriction was identified as the atrium by its activity in older embryos.

Fig.5 Pcricardial mesoderm and endocardium of same reconstruction as in figure 2 viewed from the dorsal surface. The somatic layer of mesoderm has been cut away in order to show the myocardial folds of the splanchnic layer. The arteries are cut open_ to show the extent of their lumen.

The myocardium corresponds to the endocardium inhaving a single median portion and two lateral portions. It is formed by an infolding of the splanchnic mesoderm (fig. 5).

The infolding of the median portion is scarcely distinguishable at this stage. The folds of each lateral plate form an in» complete tube which partially surrounds the endocardial tube. Figure 6 a section cut through both hearts of the embryo used for reconstruction. It illustrates the arrangement of cells and relative size of the parts. Occasional strands of protoplasm cross the space between the endocardium and myocardium, but they are much less frequently seen in the living embryo than one would expect from the appearance of fixed specimens. There is a slight thickening and constriction of the myocardium at the point where the endocardial projections mark the A-V junction.

Fig.6 Photomicrograph of section of 9-day 16-hour rat embryo, through lateral heart prin:1o1'dia.. Same embryo used for reconstruction of figures 1 to 5. X 130.

The heart is bilaterally symmetrical at this stage. The two slides are mirror images of each other, but certain slight differences may be soon, particularly in the living embryo. They foreshadow greater differences which become manifest in later development. The right endocardial tube is more sharply defined and its diameter more uniform than the left. The central portion of the left tube is slightly dilated or saccular. The lumen of the right often extends farther into the median lainina. The right side usually gives theimpression of being better developed morphologically than the left.

Preliminary experiments were performed on a number of litters in order to discover at what and in what area the first contractions occurred. All the embryos obtained from -each litter which were suitable for study (usually from four to six) were examined for short periods in rotation. A record was kept of the age, length of time in culture, and the presence and location of cardiac contractions. In the embryos wh.ich developed most normally, the portion of the heart first seen in activity was the left outer or lateral fold of the ventricular myocardium near the A—V constriction at a stage of development corresponding to figure 8. Independent activity began in the right heart approximately 2 hours later than in the left.

In some of the cultures, although the embryos appeared uninjured, the myocardium of but one side contracted. In others both sides were active, but they failed to unite subsequently into a single heart. This effect was interpreted as the result of uneven mechanical pressure, because it had been found in earlier experiments (Gross, ’35) that changes of this kind could alter the course of development of the heart. These embryos were not accepted as the primary source of data for determining the origin of contraction, but they provided valuable con~ firmatory evidence. For example, in all the cases in which the left heart contracted at any time, twenty-two in number, it was the first to be found in action. The right showed activity first in but two cases and in both of them the left heart was never seen in contraction.

After the correct stage of development and the first active portion of the heart had been determined, it was possible to set up a somewhat younger embryo (fig. 7) for continuous observation. The culture was left in the incubator for 2 hours to allow the plasma to clot and the embryo to become adjusted to its new environment. It was then placed on the stage of a microscope enclosed in an incubator at 3800. and observed with a 40 X objective and 15 X oculars. No motion of the myocardial cells could be detected. Cinematographs were taken of the heart region and observation with the microscope resumed.

At the end of 30 minutes of continuous observation, during which no motion could be detected, a slight twitching of one or two cells was seen in the lateral Wall of the ventricular portion of the left heart near the A—V junction. The excursion of these first contractions was so slight that it was difficult to be certain that they were all observed, but those which were recognized came with surprising regularity. In 1.0 minutes the excursion had increased so that counting was feasible. The rhythm was then regular and contractions occurred at the rate of 37 perminut-e. After records were made of the left heart, the right was examined carefully but no motion could be seen. Continuous observation was discontinued, but the right heart was examined at intervals. No activity was seen until 2 hours had elapsed. Its first contractions were regular but less frequent, by 2 or 3 contractions, than those of the left. During these 2 hours the rate of the left side had increased gradually to 43 per minute. The difference between this increasedratc and the beginning rate of the right side was sufficiently great to make the independence of rhythm on the two sides quite obvious.

Fig. 7 Living rat embryo approximately 9 days 12 hours. Photograph. X 25.

Gradually, all the ventricular myocardium of both sides became involved in the contraction. The spread of activity was first along the outer or convex wall toward the median line and then across the tube to take in the inner or concave wall. By the time all the myocardium surrounding the endocardial tube was active, a wave or peristaloid action suggested itself and was strikingly confirmed in slow-motion cinematographs. The wave began in the portion nearest the A—V constriction and travelled toward the median region. The tube on the venous side of the constriction, i.e., the atrium, remained inactive.

Morphological development accompanied the changes in activity. The pericardial cavity increased surprisingly in its extent. The lumen of the endocardial tubes extended farther toward the midline. The myocardial tubes lengthened aI1d increased in diameter. The fold in the median part of the myocardium became as distinct as the lateral folds so that it united the lateral or convex walls of the lateral myocardial. tubes into a single saccular ventricle. A similar fold connecting the inner or lesser curvatures could not be distinguished because of its proximity to the foregut portal and because of the openings of the aortic arches. The contraction gradually involved more and more of the median portion until it finally spread across the midline. The independent activity of the right side was then suppressed and the peristaltoid Wave travelled from the A-V region of the left side to the A—V region of the right. In one of the preliminary eases, the right and left hearts became synchronized before motion was observed in the median portion of the myocardium.

The early activity was observed in nine embryos. In general, all were similar to the case just described. The rates of the first contractions varied from 34 to 4.2, at 38°C. lrregularities such as intermittence and temporary cessation of contraction were observed, but a complete irregularity was only observed after the embryos had been in culture for more than 48 hours. The irregularities in fresh cultures could be explained by 0I1VlI"OIl.1’I1eI1lZal_Cl1a]f1g€S in all cases. Wlien the heart was beginni11g its activity it was extremely susceptible to changes in temperature and mechanical agitation, both of which caused temporary cessation of the beat, frequently followed by an abntormalloy high rate. A Variation in temperature of 4 or 5° sometimes changed the rate by eight or ten eontraotions per minute. Whell the cultures were undisturbed for a period of 10 minutes at a eoristant temperature, the rhythm became regular and the rates agtr-eed reasonaibly well with the rates of other embryos at the same stage of development.

Fig. 8 Living rat e-mbryonie Vesicle a.pproximate.1y 9 days 14 hours. Drawing from sketelies made im1'nodi:'1te1y after removal from uterus.

The two lateral hearts were slightly different, bothin form and activity. The left side had a more rapid rate than the right except in cases which appeared abnormal. As the left side developed it tended to become saccular and its contractions were more sudden and less sustained thanthose of the right. T.l‘.l,0 right tended to retain its tubular appearance and the wave of contraction travelled more slowly so that it gave the impression of a more powerful constriction. Of the nine embryos observed, three formed single hearts, six formed double hearts. The failure of the two hearts to join has been explained (Gross, ’35) as due to pressure against the cover glass. When the two hearts remained separated, the differences between them became exaggerated as the cultures developed.

Fig.9 Rat embryonic vesicle, after 16 hours in hanging drop culture. Lateral hearts were contracting independently. X 40. '

In all cases in which the single median ventricle was formed, the resulting structure was saccular, rather than tubular though a clearly tubular form, such as occurs in the chick, was not to be expected in a mammal, the saecular form in these embryos may have been exaggerated by the conditions in culture. Some distortion was always caused by fluid changes in the cultures. W'ithin 2 or 3 minutes after removal from tl1e uterus, there was as loss of fluid from all the cavities in the embryonic vesicle. It appeared shrunken and slightly more opaque. After 2 hours in culture, the volume of the vesicle was restored but the resulting form was abnormally spherical. The change in shape of the vesicle becomes clear in a comparison of figure 8 which is a drawing based upon sketches made immediately after removal from the uterus and figure 9 which is a drawing after 16 hours in culture.

The formation of a continuous endothelial lumen appeared to be a very important factor. In normal development, the lumen of the aorta extends through the first aortic arches to that of the heart shortly before the ventricle becomes as single structure. The lumen was not established in most of the cultured embryos. In the few which formed a lumen, development of the heart greatly surpassed that of the other embryos. In one case of failure of the right and left hearts to unite, each heart became connected with the aorta of its own side. Development continued until it appeared that the hearts would have forced the blood into circulation if the blood vessels had formed their proper connections.

Circulation was not observed in any of these embryos. The connections between arteries and veins were not patent. The examination of older embryos soon after removal from the uterus indicated that in normal development the circulation does not begin until the embryo has developed approximately 12 hours beyond the stage of first contraction.

No cytological changes in the cells of the n1yocaI'dium could be distinguished as a result of their earliest contraction. In the living hearts, the shape of the cells remained the same and no rearrangement of mitochondria or formation of fibrillae was observed. Since a knowledge of changes accompanying the initiation of activity in these cells is vesry important for the cyttologsicals backg*1°ound of muscular contraction, a detailed stiudly of fixed material l1as been undertal«:eI1 and will be reported later.


Our o«bservations with the rat confirm those witli the chick by Sabin*(’20), J ohnstone ( ’25) and Patten ("33) and those with Amblystoina by Copenliaver (’3T), that the lirst portion of the heart which becomes active is the primitive ventricle. Sabin states that the firstcontractions have a 1'of.;f11la1' rl1}*tl1m and J ohnstone implies the same ‘Wl'1(-}1’l. he speaks of the rhytllniic actsivity, but Patten reports that they do not appear regular when recorded by a method more precise than observation th1'o1ig*h the microscope. The author used Patten”s method of superimposing eiilargqerl cinematographs of the heart before contraction was observed, but was unable to LllSt-lI.1g‘l1lSl1 earlier movements. It possible that the 16—mm. film used by the author gave less accurate results than the larger film used by Patten. lint Arnblystoina, Copenliaver (pE¥I‘SOI1ELl'C-OII1111I11'llCZ1‘[-i011) found that the first observed contractions had a regulasr rhythm in the niajority of cases. lr1*egL1larity and intermititenee were recorded in some cases and he raises the question as to Whether these embryos were shsowing normal activity. Our observatisons with the rat, as far as they have g'rone._. asgree with those of Sabin and Copenhaver that the earliest contractions tend to have a reg*nla_r .1‘l'1}"’l3l1II1.

In a brief report of some of the earlier p1‘GllII1l.I1}1}j'}’ experiments (Gross, 137), the first contractions were giveii a rate more rapid than that contained in this eorninunieation. Our more recent observations were made on a lar,g'er number of embryos and the experimental conditions were more caref1,1llj;* controlled during“ continuous 0l”)S@1‘VEltl011. ‘We conclude, therefore, that the preliniinary rate was too l1.ig;l1, p1"oli)a.bljJ because it was based in part on E‘.Tfil.)'!"':fJOS which had passed the stage of earliest contraction.

Sabin, Johnstone and Patten all found that the right side of the heart initiated contraction in the chick. Copenhaver observed the first contraetions on one side in seven out of twenty-four Anflilystoma embryos. In six of these the first motion was lirnited to the left side and in one it was tlefinitely limited to the riglit side. Appareiitly the first contractions in}7S'tOI11€t can appear on either side and very quickly exs tend over both sides. In the rat, We found that the left side became active first except in those cases in which there was reason to believe that this side had been retarded or suppressed.

Cardiacv activity is developed more precociously in the rat than in the chick and ???? In both the latter forms, the first contractions were observed after the lateral primordia had fused into a siiigle tubular heart, whereas in the rat they occurred While the lateral hearts were still separated. In the rat, moreover, the first contractions appear in the 3—so1nite stage, While in the chick tfhey a1t)pea1ds' in the 10-sornite stage and in A1nblyston1a between stagfes 33 and 34 (16 to 18 sornites). Not only does the activity begin before the ventricle is at Sillgl-G ()1'.’g&Il., but the two parts develop independenthv and each has its own power of 1:'h;vtl1micvatl contraction. It is not possible to say with c.ertaint.v that this precoeitjg occurs in normal development in utero because the 001'l(lit.iO1’1E_-_’.. in vitro may introduce abnormalities. 011 the other hand, in einliryos examined soon after rernovalt from the uterus, the independent E1.(3-t‘iVlt-If of the two sides was observed if the rniddle cardiac plate had not developed, and the whole heart was sjvnchronized if the median portion had united the lateral portions into a saccular ventricle.

Sabin and Johnstone observed a ;gfr'ad11arl spread of 30-i-iVl_J[}" over the ventricle from the localized region of initiation near the veins to the orig2;in of the arteries. It first extended aluongg; the right border or ‘greater’ curvature and then along‘ the lesser curvature. Patten also observed that the ea.rliesdt acvtivit;v was on one side, but he found that the spread was irreg“ular. In fourteen of the twenty—four embryos studied, Copenhaver found that the first observed contractions involved most of the anterior two—thirds of the heart (ventricle and bulbus). Although he observed the first contractions one one side in seven cases, they were not always on the same side and apparently spread quickly over both sides. The activity in the rat heart extended from a small localized area along the lateral border or greater curvature and then across the tube to the lesser curvature. Finally all the myocardium surrounding the endocardial lumen was involved. In general this was a spread from the region near the veins to that near the arteries.

After the entire primitive ventricle had become active in the Chick, Patten observed a ‘peristaltoid’ Wave in the contraction. It travelled from the venous to the arterial end. The same kind of Wave was observed in the rat. While the lateral hearrts were still independent, the Wave travelled from venous to arterial ends as in the chick. After the median portion of the myocardium had become active, the wave travelled from side to side, i.e., from vein to vein, rather than from posterior to anterior or from veins to arteries. This difference seems to be due to the morphology of the heart after a single saecular ventricle has been formed. There is a greater and lesser curvature, as in the chick, but they extend from the A—V junction of one side to the A—V junction of the other side. The aortae open near the lesser curvature, leaving the greater curvature as the expanded and more motile portion.

Yoshinaga (’21) in his description of the development of the guinea pig heart Writes: the cranial prolongation of the lateral myocardial tubes has not been brought about by the direct e}1’t_€Tl$i011 of the first part of the myocardial tubes, but by the continuous progres~ sive differentiation into the craniomedian limb of the pericardial cavity. Tlierefore, the confluence of the myocardial tubes into a single myocardial cavity is not accomplished by the actual fusion of the bilateral myocardial tubes, followed by absorption of the septal walls.

In the rat a similar condition was found. Instead of a fusion of the two lateral myocardial tubes, there was a more or less independent growth of the median portion which eventually united them into a saccular organ.

The stage at which the hearts of other mammals begin to contract cannot be determined from morphological studies alone. The author has found several published accounts, however, which include descriptions of a stage which is sufficiently similar to that of the rat to warrant a brief discussion of the probable time of earliest cardiac activity in other mammals. Hensen (1876) described the two lateral primordia in the rabbit and guinea pig and commented on their differences from the early chick heart. Although the rabbit embryo depicted in his figures 28 and 37 is too young for beginning contraction, it is close to this stage. He traced the formation of the endoeardial tubes from scattered cells of the ‘vessel layer’ shown in his figure 37. The myocardium he derived from the visceral layer of the primitive pericardial cavity.

The rabbit has been illustrated by Bremer (’12) and Rouviere (’()4). Bremer’s figure 3 is based on a very carefully prepared recoiistruetioii of an 8%—day rabbit with 6 to 7 somites. The COflCll';10I1 of the heart and endothelium eorresponds close]? to that which we have observed in the rat. The pericardium and heart of a 201—hour rabbit in Rouviere’s plate 17 , figure 1 also seem to be of the same stage.

The heart of the guinea pig embryo in Yoshinaga’s (’21) stage III (figs. 12 and 13) has a myocardium which is slightly better developed than that of the rat at the beginning contraction. The general development, however, is the same. The extent of the lumen in the endothelial tubes is similar, and it is Worthy of notice that the right side extends farther into the median region than the left, as We have smentioned in the rat. The endocardial primordium or angioblast, according to Yoshinaga, is much less extensive in the median region of the guinea pig embryos, at this stage.

The ferret embryo with 5 somites which Wlang (*1?) has given in graphic reconstruction in his figure 6 a corresponds in general to tl1e stiavge we have described in the rat. The continuity of endocardial lumen across the midline is difficult to understand because t.he lumen is interrupted in tlie lat-eral hearts. Vkle are inclined to disagree with Wa11g"s interpretation of the various parts of the vascular system. “That he has labelled vitelline vein seems to be the heart tube and the connection between the vitelline vein and aorta which he describes is apparently the aortic arch primordium.

The reconstruction of a cat embryo illustrated in figure 1 by Schulte (’16) has many resemblances to that of the rat which We have given. It is worthy of notice, however, that although this cat embryo had 8 somites, it had no foregut invagination. The author has examined the slides from which the reconstruction was made and has found that the cardiac primordia were further developed cytiologically than the reconstruction would indicate. 1t seems probable that development had gjsone sligl1tvly beyond the stage of begiriiiirig contraction.

Parker (’]5) g.iv»es a grapl1ic reconstruction (plate T, 3) of a Inarsupial embryo (Dasyurus viverrinus, 8.5 mm.) in which the heart probably had reached the stage of first contraction. The foregut and brain are represented, but there are no somites. The eendothelial tube of each lateral heart is continuous with that of the aorta of the same side through the first aortic arch. The lumen, hovvever, does not extend across the midline to form a eozmmunication between the lateral tubes. The condition of the heart in older marsupial embryos indicates that functional development. p1s*og‘I'esses farther before union into a sirigle ventricle than is the case in the rat.

No description of a human embryo in which the heart corresponds to the beginning of contraction, has been found. Such a stagewould be intermediate between embryo 5080 of Davis (’27) and the Ingalls (’20) embryo. In the former the pericardial cavity has formed but there are no myocardial folds. In the latter the folds have been partly united by the median myocardiurn. The Davis 5080 embryo has 1 somite fo.1°1r.ni11.g, the Ingalls has 2 somites. There is good reason to believe, however, that the development of the hunlan heart follows the same plan as that of other mammals and that the desired stage will be found as niore human material becomes


The beginning of contractile activity in the hearts of rat embryos was observed in hanging drop cultures of Whole embryonic vesicles. The age of the embryos was approximately 9 days 14 hours. The hearts were observed continuously f.['0II1.-"fl; hour before contraction until activity was well established.

The first contractions have a 1'e§:ula1* rhythm and a rate of .37 to 42 per minute. They are confined to as small area, three or four cells, in the lateral ventricular nrvoeardium of the left primitive heart tube. The area is near a constriction which marks the junction of the primitive atrium and ventricle.

The 1"lg'l'1t myocardial tube begins contracting in a similar fashion 2 hours after the left. its rh;vthm is 1°segulacr, but independent of and slower than the left. The contractile activity g‘I'aCl11E1-ll}? extends over the ventricular myocardium of each side until all 'i.l'1-E?'11)0'I'.'ti()1] s111**1°oL111Cli11g the endocardial lumen is involved.

The two lateral hearts become united into a single saceular ventricle by the pI‘0g”I’€SSlV=-C differentiation of the median splanehnic mesoderm. After this median inyocardium becomes active, the independent activity of the right heart is suppressed and the left side becomes the pacemaker for the whole ventricle. The rate increases ggravclually as more myocardium becomes contractile. The atrium remains motionless during this devoelopnienti and there is no C-l]'i‘(f11l‘r1.lI-.lOI1 of the blood.

The contraction has a wave-like character. In each of the lateral heart tubes before their union, it travels from the venous region, i.e., the A—V constriction, to the arterial regioii of the aortic arch primordia. In the united ventricle, it travels from the A—V junction of the left side to that of the right.

Significant II1Ol"‘pl1Ol()§__3,"'lC-Elul and functional differences between the two primitive lateral hearts occur. The embryo at the stage of beginning contraction is described from living material and wax reconstruction and compared with other mammalian embryos.

Literature Cited

BREMER, J. L. 1912 The development of the aorta and aortic arches in rabbits. ' Am. J. Anat., vol. 13, pp. 111-128.

COPEIH-IAVER., ‘W. M. 1937 Correlation in the structural and functional development. of the heart as studied by hetcroplastic grafting. Anat. Rec., vol. 67 (Suppl. no. 3), p. 12.

DAVIS, CARL L. 1927 Development of the human heart from its first appearance to the stage found in embryos of 20 paired somites. Carnegie Inst. Pub., no. see, Contrib. to Embryol., vol. 19, pp. 245434. 1

GOSS, C’. M. 1935 Double hearts produced experimentally in rat embryos. J. Exp. Zool., vol. '72, pp. 33-49.

1937 Early development of the rat heart in vitro. Anat. Rec., V01. 67 (Suppl. no. 3), p. 20.

HENSEN, V. 1876 Beobaehtungen iiber die Befruchturig und Elltwieklung des Kaninehens u-nd Meersehwe-.incliens. Zeit. f. Anat. u. Entwie-k., Bd. 1, S. 213-273 and 353-423, Heart, S. 367-369.

INGALLS, N. W. 1920 A human embryo at the beginning of segmentation, with special reference to the vascular system. Carnegie Inst. Pub., no. 27 , Contrib. Ernbryol., vol. 11, pp. 61-90.

J01’-INS'I‘O'NE., P. N. 1925 Studies on the physiological anatomy of the embryonic heart. Johns Hopkins Hosp. Bu1l., "vol. 36, pp. 299-311.

"LONG, J. A.., AND H. M. EVANS 1922 The oestrous cycle in the rat and its associated phe-I1ome11a.. Mom. Univ. California, vol. 6, pp. 14148.

NICHOLAS, J. 8., AND D. RUDNICK 1934 The development of rat embryos in tissue cultures. Proc. Nat. Acad. Sci., vol. 20, pp. 656-658.

PARKER, K. M. 1915 The early development. of the heart and anterior vessels in Marsupials, with speeial reference to Peranieles. Proe. Zool. Soc., London, pp. 459-499.

PATTEN, B. M., AND T. C. KRAMER. 1933 The initiation of contraction in the embryonic chick heart. Am. J. Anat., V01. 53, pp. 349-375.

RoUyI'fi:RE, H. 1904 Etudes sur le développement du périearde ebez le lapin. J. de l’ana.t. et de la p.hysiol., T. 40, pp. 610—~633.

SABIN, F. R. 1920 Studies on the origin of blood—vessels and of red blood corpuseles as seen in the living blastoderm of chicks during the second day of incubation. C3-1‘11i3glE3 Inst. Pub., no. 272, Contrib. Embryo1., vol. 9. pp. 213-262.

SCHULTE, II. v.W. 1916 The fusion of the cardiac analages and the formation of the cardiac loop in the cat (Fells domest.i<3a). Am. J. Anat, vol. 20, pp. 45-72.

WANG, C. C. 1917 Earliest stages of development of the blood VC'SSClS and the heart in ferret embryos. J. Anat., vol. 52, pp. 1073-185.

Yosrrlnae-A, T. 1921 A contribution to the early develop:-nent of the heart in inammalia, with special reference to the guinea pig. Anat. H-ee., vol. 21, pp. 239-308.

Cite this page: Hill, M.A. (2024, April 13) Embryology Paper - The first contractions of the heart in rat embryos. Retrieved from

What Links Here?
© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G