The first contractions of the heart in rat embryos

Goss, Charles Mayo

doi:10.1002/ar.1090700502

Cited by 84 publications

(37 citation statements)

References 7 publications

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“…Furthermore, early mammalian cardiac development is rapid compared with early chicken cardiac development. For example, in rats the first contractions are already observed before the paired primordia have fused (108); the myocardial cells are poorly coupled, which would suggest that also in the early mammalian heart tube the propagation of the impulse is slow (94,115,310).…”

Section: A Development Of Polaritymentioning

confidence: 99%

Cardiac Chamber Formation: Development, Genes, and Evolution

Moorman

Christoffels

2003

Physiological Reviews

639

526

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Moorman, Antoon F. M., and Vincent M. Christoffels. Cardiac Chamber Formation: Development, Genes, and Evolution. Physiol Rev 83: 1223-1267, 2003; 10.1152/physrev.00006.2003.—Concepts of cardiac development have greatly influenced the description of the formation of the four-chambered vertebrate heart. Traditionally, the embryonic tubular heart is considered to be a composite of serially arranged segments representing adult cardiac compartments. Conversion of such a serial arrangement into the parallel arrangement of the mammalian heart is difficult to understand. Logical integration of the development of the cardiac conduction system into the serial concept has remained puzzling as well. Therefore, the current description needed reconsideration, and we decided to evaluate the essentialities of cardiac design, its evolutionary and embryonic development, and the molecular pathways recruited to make the four-chambered mammalian heart. The three principal notions taken into consideration are as follows. 1) Both the ancestor chordate heart and the embryonic tubular heart of higher vertebrates consist of poorly developed and poorly coupled “pacemaker-like” cardiac muscle cells with the highest pacemaker activity at the venous pole, causing unidirectional peristaltic contraction waves. 2) From this heart tube, ventricular chambers differentiate ventrally and atrial chambers dorsally. The developing chambers display high proliferative activity and consist of structurally well-developed and well-coupled muscle cells with low pacemaker activity, which permits fast conduction of the impulse and efficacious contraction. The forming chambers remain flanked by slowly proliferating pacemaker-like myocardium that is temporally prevented from differentiating into chamber myocardium. 3) The trabecular myocardium proliferates slowly, consists of structurally poorly developed, but well-coupled, cells and contributes to the ventricular conduction system. The atrial and ventricular chambers of the formed heart are activated and interconnected by derivatives of embryonic myocardium. The topographical arrangement of the distinct cardiac muscle cells in the forming heart explains the embryonic electrocardiogram (ECG), does not require the invention of nodes, and allows a logical transition from a peristaltic tubular heart to a synchronously contracting four-chambered heart. This view on the development of cardiac design unfolds fascinating possibilities for future research.

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Section: A Development Of Polaritymentioning

confidence: 99%

Cardiac Chamber Formation: Development, Genes, and Evolution

Moorman

Christoffels

2003

Physiological Reviews

639

526

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“…1,2,7,10,11 In the mouse, a patent endocardial tube is formed at Ϸ6 S, the primitive heart is linked to the intact dorsal aortas by 5 S to 7 S, and the heart appears "capable of maintaining some circulation of the blood" (page 44) 10 at 13 S to 20 S. 10,12 Other investigators have noted weak, irregular cardiac contractions at 3 S to 4 S, with "fairly regular" (page 78) 2 contractions by 5 S to 6 S, but circulation was not assessed. 2 Although undoubtedly we are not observing the very first contractions of cardiomyocytes, which likely involve only a few cells, we are observing very early whole-organ contraction with UBM.…”

Section: Initiation Of the Heartbeatmentioning

confidence: 99%

“…However, little is known about the fundamental questions of when cardiac function and blood flow are first established. Data have come largely from invasive methods 1,2 that disrupt the normal physiological milieu, and scant data exist in the mouse, the primary model of mammalian development. 2,3 Functional circulation is composed of the beating heart, vascular bed, and blood cells.…”

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confidence: 99%

Onset of Cardiac Function During Early Mouse Embryogenesis Coincides With Entry of Primitive Erythroblasts Into the Embryo Proper

Phoon

Aristizábal

et al. 2003

Circulation Research

145

128

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When cardiac function and blood flow are first established are fundamental questions in mammalian embryogenesis. The earliest erythroblasts arise in yolk sac blood islands and subsequently enter the embryo proper to initiate circulation. Embryos staged 0 to 30 somites (S) were examined in utero with 40-to 50-MHz ultrasound biomicroscopy (UBM)-Doppler, to determine onset of embryonic heartbeat and blood flow and to characterize basic physiology of the very early mouse embryonic circulation. A heartbeat was first detected at 5 S, and blood vascular flow at 7 S. Heart rate, peak arterial velocity, and velocity-time integral showed progressive increases that indicated a dramatically increasing cardiac output from even the earliest stages. In situ hybridization revealed an onset of the heartbeat coincident with the appearance of yolk sac-derived erythroblasts in the embryo proper at 5 S. Early maturation of the circulation follows a tightly coordinated program.T he heart is the first organ to develop during embryogenesis. However, little is known about the fundamental questions of when cardiac function and blood flow are first established. Data have come largely from invasive methods 1,2 that disrupt the normal physiological milieu, and scant data exist in the mouse, the primary model of mammalian development. 2,3 Functional circulation is composed of the beating heart, vascular bed, and blood cells. The yolk sac is the earliest and only source of hematopoietic progenitors in the gastrulating mouse embryo. 4 Primitive erythroid progenitors originate in the yolk sac beginning at the late primitive streak stage, before the establishment of circulation in the embryo proper. 4,5 These progenitors give rise to maturing primitive erythroblasts within yolk sac blood islands, which then enter the embryo proper to initiate circulation.We hypothesized that the timing of onset of heartbeat and erythroid cell migration are tightly coordinated. We sought therefore to characterize time points and basic physiology of the very early mouse embryonic circulation using ultrasound biomicroscopy (UBM)-Doppler, a high-frequency echocardiography system developed in our laboratory that allows in utero study of the embryonic mouse circulation. 6 -9 Materials and MethodsThe imaging and whole-mount in situ hybridization protocols have been reported elsewhere, with minor modifications to study earlystage embryos. UBM-Doppler imaging was performed using a semi-invasive in utero approach, exteriorizing the uterus but otherwise maintaining all circulatory systems intact, in close-to-physiological conditions (see the online data supplement available at http://www.circresaha.org for an expanded Materials and Methods section). Results UBM-Doppler Imaging of Early-Stage EmbryosDespite the need for maternal anesthesia, our results indicate that semi-invasive UBM-Doppler yields physiologically relevant data and is uniquely suited to study early embryonic cardiovascular function (see the online data supplement for additional Results). Initiation of Early...

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“…Nicholson (SUNY, Buffalo, N.Y.) kindly provided us with two additional rabbit antibodies. The first antibody was raised against amino acids [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] of the amino terminal domain of connexin43, and the second antibody was raised against amino acids 302-319 at the carboxyl terminal domain of connexin43. The latter antibody was affinity-purified.…”

Section: Antibodiesmentioning

confidence: 99%

Spatial distribution of connexin43, the major cardiac gap junction protein, in the developing and adult rat heart.

Kempen

Fromaget

Gros

et al. 1991

Circulation Research

175

100

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The developmental appearance and spatial distribution pattern of gap junctions were studied in prenatal and adult rat hearts. Gap junctions were visualized immunohistochemically with an antibody raised against a unique cytoplasmic epitope of connexin43, and the spatial distribution pattern was determined by three-dimensional reconstruction. The results demonstrate that from embryonic day 13 onward, connexin43 becomes detectable immunohistochemically in the myocardium of atria and ventricles. No expression is initially detectable in the myocardium of the sinus venosus, the sinoatrial node, the posterior wall of the atrium and pulmonary veins, the interatrial septum, the atrioventricular canal, including atrioventricular node and bundle, the interventricular septum, and the outflow tract. The developmental increase in the density of gap junctions in atria and ventricles of prenatal hearts correlates well with the reported developmental increase in conduction velocity. Whereas connexin43 becomes expressed in the derivatives of the sinus venosus (except for the sinoatrial node) and in the subepicardial layer of the ventricular free wall shortly before birth, it remains undetectable in the atrioventricular node and bundle and the proximal part of the ventricular conduction tissue, even in the adult heart. The apparent absence of an abundant expression of connexin43 at a location with a supposedly high conduction velocity (i.e., the atrioventricular bundle and bundle branches) is unexpected. These observations were confirmed in studies of the adult mouse heart, which showed, in addition, that connexin32 is not expressed in any part of the heart. (Circulation Research 1991;68:1638-1651 In the "primary myocardium" of early, tubular hearts the conduction of the depolarizing impulse, which initiates contraction of the myocytes, is slow and spreads uniformly, resulting in a peristaltic contraction pattern. Although the conduction velocity in the working myocardium of atria and ventricles increases during development, it remains low in the adjacent regions (sinus venosus, atrioventricular canal, and outflow tract, i.e., the remaining primary myocardium). As a result, the cardiac tube consists of a series of segments with alternatingly slow and relatively fast conduction velocities. These developmental changes in regional conduction velocity and contraction pattern are best documented for avian embryosl-5 but are believed to occur also in the embryonic mammalian heart.6 Since cardiac gap junctions are generally believed to be responsible for the direct electrical coupling between myocardial cells (for recent reviews see References 7-9), we hypothesized that the selective formation of gap junctions in working myocardium might explain the gradual appearance of a more rapid conduction of the depolarizing impulse in the developing atria and ventricles. As a first step to test this hypothesis, we have studied the spatial distribution of gap junctions in the developing rat heart. A gap junction consists of an array of cell-to-cell...

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The first contractions of the heart in rat embryos

Cited by 84 publications

References 7 publications

Cardiac Chamber Formation: Development, Genes, and Evolution

Cardiac Chamber Formation: Development, Genes, and Evolution

Onset of Cardiac Function During Early Mouse Embryogenesis Coincides With Entry of Primitive Erythroblasts Into the Embryo Proper

Spatial distribution of connexin43, the major cardiac gap junction protein, in the developing and adult rat heart.

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