How does the tubular embryonic heart work? Looking for the physical mechanism generating unidirectional blood flow in the valveless embryonic heart tube.

The heart is the first organ to function in vertebrate embryos. The human heart, for example, starts beating around the 21st embryonic day. During the initial phase of its pumping action, the embryonic heart is seen as a pulsating blood vessel that is built up by (1) an inner endothelial tube lacking valves, (2) a middle layer of extracellular matrix, and (3) an outer myocardial tube. Despite the absence of valves, this tubular heart generates unidirectional blood flow. This fact poses the question how it works. Visual examination of the pulsating embryonic heart tube shows that its pumping action is characterized by traveling mechanical waves sweeping from its venous to its arterial end. These traveling waves were traditionally described as myocardial peristaltic waves. It has, therefore, been speculated that the tubular embryonic heart works as a technical peristaltic pump. Recent hemodynamic data from living embryos, however, have shown that the pumping function of the embryonic heart tube differs in several respects from that of a technical peristaltic pump. Some of these data suggest that embryonic heart tubes work as valveless "Liebau pumps." In the present study, a review is given on the evolution of the two above-mentioned theories of early cardiac pumping mechanics. We discuss pros and cons for both of these theories. We show that the tubular embryonic heart works neither as a technical peristaltic pump nor as a classic Liebau pump. The question regarding how the embryonic heart tube works still awaits an answer.

In vivo imaging of the cyclic changes in cross-sectional shape of the ventricular segment of pulsating embryonic chick hearts at stages 14 to 17: a contribution to the understanding of the ontogenesis of cardiac pumping function.

The cardiac cycle-related deformations of tubular embryonic hearts were traditionally described as concentric narrowing and widening of a tube of circular cross-section. Using optical coherence tomography (OCT), we have recently shown that, during the cardiac cycle, only the myocardial tube undergoes concentric narrowing and widening while the endocardial tube undergoes eccentric narrowing and widening, having an elliptic cross-section at end-diastole and a slit-shaped cross-section at end-systole. Due to technical limitations, these analyses were confined to early stages of ventricular development (chick embryos, stages 10-13). Using a modified OCT-system, we now document, for the first time, the cyclic changes in cross-sectional shape of beating embryonic ventricles at stages 14 to 17. We show that during these stages (1) a large area of diminished cardiac jelly appears at the outer curvature of the ventricular region associated with formation of endocardial pouches; (2) the ventricular endocardial lumen acquires a bell-shaped cross-section at end-diastole and becomes compressed like a fireplace bellows during systole; (3) the contracting portions of the embryonic ventricles display stretching along its baso-apical axis at end-systole. The functional significance of our data is discussed with respect to early cardiac pumping function.

Optical coherence tomography: a new high-resolution imaging technology to study cardiac development in chick embryos.

BACKGROUND: Optical coherence tomography (OCT) is a depth-resolved, noninvasive, non-destructive imaging modality, the use of which has yet to be fully realized in developmental biology. METHODS AND RESULTS: We visualized embryonic chick hearts at looping stages using an OCT system with a 22 micro m axial and 27 micro m lateral resolution and an acquisition rate of 4000 A-scans per second. Normal chick embryos from stages 14 to 22 and sham-operated and cardiac neural crest-ablated embryos from stages 15 and 18 were scanned by OCT. Three-dimensional data sets were acquired and processed to create volumetric reconstructions and short video clips. The OCT-scanned embryos (2 in each group) were photographed after histological sectioning in comparable planes to those visualized by OCT. The optical and histological results showing cardiovascular microstructures such as myocardium, the cardiac jelly, and endocardium are presented. CONCLUSIONS: OCT is a powerful imaging modality which can provide new insight in assessing and understanding normal and abnormal cardiac development in a variety of animal models.

Shortened outflow tract leads to altered cardiac looping after neural crest ablation.

BACKGROUND: Congenital conotruncal malformations frequently involve dextroposed aorta. The pathogenesis of dextroposed aorta is not known but is thought to be due to abnormal looping and/or wedging of the outflow tract during early heart development. We examined the stage of cardiac looping in an experimental model of dextroposed aorta to determine the embryogenesis of this conotruncal malformation. METHODS AND RESULTS: Hearts were examined from neural crest-ablated embryos by using videocinephotography, scanning electron microscopy, and histological sections. The inflow and outflow limbs of the looped cardiac tube were malpositioned with respect to each other, the inner curvature was diminished, and the outflow limb was straighter and displaced cranially in a manner consistent with diminished length. The altered length could be explained by a significant reduction in the number of cells added to the myocardium of the distal outflow tract from the secondary heart field. CONCLUSIONS: The data are consistent with research showing that normal looping and wedging are essential for normal alignment of the aorta with the left ventricle. These processes are abnormal in neural crest-ablated embryos because of a failure of the outflow tract to lengthen by the addition of myocardial cells from the secondary heart field.

A detailed atlas of chick heart development in vivo.

Various model organisms such as mouse, xenopus, or zebrafish embryos have been studied in the past to gain insight into the complex processes driving normal and abnormal development of the vertebrate heart. Despite the fact that the chicken embryo has been a favored classic model system used by embryologists and cardiovascular scientists for centuries to illustrate the principles of basic vertebrate embryology and cardiovascular development, so far, no one has provided a thorough documentation of heart development in this model from early visual stages to the stage of a completely formed heart with (a) images and (b) video recordings of beating hearts. However, in vivo documentation of heart development stages is indispensable because the initially tubular embryonic heart not only undergoes dramatic morphological changes, but also intriguing functional changes during cardiogenesis, which, only if they follow and remain within the normal developmental pathway, lead to the establishment of the normal four-chambered heart. In this work we present the first reference catalogue of cardiac development in vivo with (1) 25 plates of high resolution colour images in different views from Hamburger-Hamilton (HH)-stage 12 (day 2, relatively straight heart tube, early myocardial contractions) through HH-stage 35 (day 9, four-chambered heart) in end-diastole and end-systole, including a plate with an overview of all these stages; (2) collection of 82 video recordings of beating hearts in different views corresponding to the stages shown in the plates.

Removal of temporary pacemaker after cardiac surgery in infants: A harmless procedure?

External pacemakers (PM) via temporary epicardial leads are routinely applied to infants and children during heart surgery, which usually, after an uneventful post surgical course, can be removed without complications. We report about two infants with complex congenital heart defects after cardiac surgery (arterial switch and Mustard operation for Transposition of the great arteries). Intraoperative these patients received temporary epicardial PM wires. Thirteen and 18 days post surgery, respectively, the PM wires were removed under electrocardiogram (ECG) monitoring. The patients showed acute ECG changes in terms of significant ST elevation during and after removing their pacing wires. Clinically, patients were stable and subsequent echocardiographic examination showed no evidence of myocardial dysfunction or pericardial effusion. In the course of time, patients showed no signs of arrhythmia or abnormal ECG changes. The decision to place temporary pacing wires during the cardiac surgery in patients with congenital heart defects should be considered carefully and their removal should occur under ECG monitoring as soon as the situation of the patient allows. It should be taken into consideration that a complication like this case may be related to delayed removal of temporary PM's leads.

Integration of an optical coherence tomography (OCT) system into an examination incubator to facilitate in vivo imaging of cardiovascular development in higher vertebrate embryos under stable physiological conditions.

High-resolution in vivo imaging of higher vertebrate embryos over short or long time periods under constant physiological conditions is a technically challenging task for researchers working on cardiovascular development. In chick embryos, for example, various studies have shown that without appropriate maintenance of temperature, as one of the main environmental factors, the embryonic heart rate drops rapidly and often results in an increase in regurgitant flow. Hemodynamic parameters are critical stimuli for cardiovascular development that, for a correct evaluation of their developmental significance, should be documented under physiological conditions. However, previous studies were mostly carried out outside of an incubator or under suboptimal environmental conditions. Here we present, to the best of our knowledge, the first detailed description of an optical coherence tomography (OCT) system integrated into an examination incubator to facilitate real-time in vivo imaging of cardiovascular development under physiological environmental conditions. We demonstrate the suitability of this OCT examination incubator unit for use in cardiovascular development studies by examples of proof of principle experiments. We, furthermore, point out the need for use of examination incubators for physiological OCT examinations by documenting the effects of room climate (22°C) on the performance of the cardiovascular system of chick embryos (HH-stages 16/17). Upon exposure to room climate, chick embryos showed a fast drop in the heart rate and striking changes in the cardiac contraction behaviour and the blood flow through the vitelline circulation. We have documented these changes for the first time by M-mode OCT and Doppler M-mode OCT.

High-resolution in vivo imaging of the cross-sectional deformations of contracting embryonic heart loops using optical coherence tomography.

The embryonic heart tube consists of an outer myocardial tube, a middle layer of cardiac jelly, and an inner endocardial tube. It is said that tubular hearts pump the blood by peristaltoid contractions. The traditional concept of cardiac peristalsis sees the cyclic deformations of pulsating heart tubes as concentric narrowing and widening of tubes of circular cross-section. We have visualized the cross-sectional deformations of contracting embryonic hearts in chick embryos (HH-stages 9-17) using real-time high-resolution optical coherence tomography. Cardiac contractions are detected from HH-stage 10 onward. During the cardiac cycle, the myocardial tube undergoes concentric narrowing and widening while the endocardial tube undergoes eccentric narrowing and widening, having an elliptic cross-section at end-diastole and a slit-shaped cross-section at end-systole. The eccentric deformation of the endocardial tube is the consequence of an uneven distribution of the cardiac jelly. Our data show that the cyclic deformations of pulsating embryonic heart tubes run other than originally thought. There is evidence that heart tubes of elliptic cross-section might pump blood with a higher mechanical efficiency than those of circular-cross section. The uneven distribution of cardiac jelly seems to prefigure the future AV and cono-truncal endocardial cushions.

Construction and establishment of a new environmental chamber to study real-time cardiac development.

Heart development, especially the critical phase of cardiac looping, is a complex and intricate process that has not yet been visualized "live" over long periods of time. We have constructed and established a new environmental incubator chamber that provides stable conditions for embryonic development with regard to temperature, humidity, and oxygen levels. We have integrated a video microscope in the chamber to visualize the developing heart in real time and present the first "live" recordings of a chick embryo in shell-less culture acquired over a period of 2 days. The time-lapse images we show depict a significant time window that covers the most critical and typical morphogenetic events during normal cardiac looping. Our system is of interest to researchers in the field of embryogenesis, as it can be adapted to a variety of animal models for organogenesis studies including heart and limb development.

Lower abdominal inflammatory myofibroblastic tumor -an unusual presentation- a case report and brief literature review.

A 9-year-old girl presented with lethargy, malaise & chest pain. Her blood counts confirmed hypochromic microcytic anemia. She was prescribed iron supplements. Subsequently she was admitted to our hospital with fever and increasing chest and abdominal pain. She was treated with antibiotics, and a diagnosis of "early chest infection" was made. Over the following 2 weeks she failed to improve, and her anemia worsened. She was readmitted, and found to have a mass in her lower abdomen with pressure symptoms on her bowel and bladder. A white-cell scan showed increased uptake in right lower quadrant. An ultrasound and a CT scan confirmed a mass adjacent to her bladder. Needle biopsy showed it to be an unusual localization of an inflammatory myofibroblastic tumor (IMT) of cecum. A presentation with chest pain, fever, anemia and pressure symptoms was highly unusual of a lower abdominal IMT mass. She had a successful excision of the tumor, with resolution of her symptoms.