Biomedical subjects

Maria Reckova

Publications and source records attributed to Maria Reckova.

7 recordsLinked to original sources

PubMed2005

Optical mapping of electrical activation in the developing heart.

Specialized conduction tissues mediate coordinated propagation of electrical activity through the adult vertebrate heart. Following activation of the atria, the activation wave is slowed down in the atrioventricular canal or node, after which it spreads rapidly into the left and right ventricles via the His-Purkinje system (HPS). This results in the ventricles being activated from the apex toward the base, which is a hallmark of HPS function. The development of mature HPS function follows significant phases of cardiac morphogenesis. Initially, the cardiac impulse propagates in a slow, linear, and isotropic fashion from the sinus venosus at the most caudal portion of the tubular heart. Although the speed of impulse propagation gradually increases as it travels toward the anterior regions of the heart tube, the actual sequence of ventricular activation in the looped heart proceeds in the same direction as blood flow. Eventually, the immature base-to-apex sequence of ventricular activation undergoes an apparent reversal, changing to the mature apex-to-base pattern. Using an optical mapping approach, we demonstrate that the timing of this last transition shows striking dependence on hemodynamic loading of the ventricle, being accelerated by pressure overload and delayed in left ventricular hypoplasia. Comparison of chick and mammalian hearts revealed some striking similarities as well as key differences in the timing of such events during cardiac organogenesis.

Action Potentials↗

PubMed2004

Hemodynamic-dependent patterning of endothelin converting enzyme 1 expression and differentiation of impulse-conducting Purkinje fibers in the embryonic heart.

Impulse-conducting Purkinje fibers differentiate from myocytes during embryogenesis. The conversion of contractile myocytes into conduction cells is induced by the stretch/pressure-induced factor, endothelin (ET). Active ET is produced via proteolytic processing from its precursor by ET-converting enzyme 1 (ECE1) and triggers signaling by binding to its receptors. In the embryonic chick heart, ET receptors are expressed by all myocytes, but ECE1 is predominantly expressed in endothelial cells of coronary arteries and endocardium along which Purkinje fiber recruitment from myocytes takes place. Furthermore, co-expression of exogenous ECE1 and ET-precursor in the embryonic heart is sufficient to ectopically convert cardiomyocytes into Purkinje fibers. Thus, localized expression of ECE1 defines the site of Purkinje fiber recruitment in embryonic myocardium. However, it is not known how ECE1 expression is regulated in the embryonic heart. The unique expression pattern of ECE1 in the embryonic heart suggests that blood flow-induced stress/stretch may play a role in patterning ECE1 expression and subsequent induction of Purkinje fiber differentiation. We show that gadolinium, an antagonist for stretch-activated cation channels, downregulates the expression of ECE1 and a conduction cell marker, Cx40, in ventricular chambers, concurrently with delayed maturation of a ventricular conduction pathway. Conversely, pressure-overload in the ventricle by conotruncal banding results in a significant expansion of endocardial ECE1 expression and Cx40-positive putative Purkinje fibers. Coincident with this, an excitation pattern typical of the mature heart is precociously established. These in vivo data suggest that biomechanical forces acting on, and created by, the cardiovascular system during embryogenesis play a crucial role in Purkinje fiber induction and patterning.

Animals↗

PubMed2004

Developmental transitions in electrical activation patterns in chick embryonic heart.

The specialized conduction tissue network mediates coordinated propagation of electrical activity through the adult vertebrate heart. Following activation of the atria, the activation wave is slowed down in the atrioventricular canal or node, then spreads rapidly into the left and right ventricles via the His-Purkinje system (HPS). This results in the ventricle being activated from the apex toward the base and is thought to represent HPS function. The development of mature HPS function in embryogenesis follows significant phases of cardiac morphogenesis. Initially, cardiac impulse propagates in a slow, linear, and isotropic fashion from the sinus venosus at the most caudal portion of the tubular heart. Although the speed of impulse propagation gradually increases, ventricular activation in the looped heart still follows the direction of blood flow. Eventually, the immature base-to-apex sequence of ventricular activation undergoes an apparent reversal, maturing to apex-to-base pattern. The embryonic chick heart has been studied intensively by both electrophysiological and morphological techniques, and the morphology of its conduction system (which is similar to mammals) is well characterized. One interesting but seldom studied feature is the anterior septal branch (ASB), which came sharply to focus (together with the rest of the ventricular conduction system) in our birthdating studies. Using an optical mapping approach, we show that ASB serves to activate ventricular surface between stages 16 and 25, predating the functionality of the His bundle/bundle branches. Heart morphogenesis and conduction system formation are thus linked, and studying the abnormal activation patterns could further our understanding of pathogenesis of congenital heart disease.

Action Potentials↗

PubMed2003

Hemodynamics is a key epigenetic factor in development of the cardiac conduction system.

The His-Purkinje system (HPS) is a network of conduction cells responsible for coordinating the contraction of the ventricles. Earlier studies using bipolar electrodes indicated that the functional maturation of the HPS in the chick embryo is marked by a topological shift in the sequence of activation of the ventricle. Namely, at around the completion of septation, an immature base-to-apex sequence of ventricular activation was reported to convert to the apex-to-base pattern characteristic of the mature heart. Previously, we have proposed that hemodynamics and/or mechanical conditioning may be key epigenetic factors in development of the HPS. We thus hypothesized that the timing of the topological shift marking maturation of the conduction system is sensitive to variation in hemodynamic load. Spatiotemporal patterns of ventricular activation (as revealed by high-speed imaging of fluorescent voltage-sensitive dye) were mapped in chick hearts over normal development, and following procedures previously characterized as causing increased (conotruncal banding, CTB) or reduced (left atrial ligation, LAL) hemodynamic loading of the embryonic heart. The results revealed that the timing of the shift to mature activation displays striking plasticity. CTB led to precocious emergence of mature HPS function relative to controls whereas LAL was associated with delayed conversion to apical initiation. The results from our study indicate a critical role for biophysical factors in differentiation of specialized cardiac tissues and provide the basis of a new model for studies of the molecular mechanisms involved in induction and patterning of the HPS in vivo.

Animals↗

PubMed2003

Spatiotemporal pattern of commitment to slowed proliferation in the embryonic mouse heart indicates progressive differentiation of the cardiac conduction system.

Patterns of DNA synthesis in the developing mouse heart between ED7.5-18.5 were studied by a combination of thymidine and bromodeoxyuridine labeling techniques. From earliest stages, we found zones of slow myocyte proliferation at both the venous and arterial poles of the heart, as well as in the atrioventricular region. The labeling index was distinctly higher in nonmyocardial populations (endocardium, epicardium, and cardiac cushions). Ventricular trabeculae showed lower proliferative activity than the ventricular compact layer after their appearance at ED9.5. Low labeling was observed in the pectinate muscles of the atria from ED11.5. The His bundle, bundle branches, and Purkinje fiber network likewise were distinguished by their lack of labeling. Thymidine birthdating (label dilution) showed that the cells in these emerging components of the cardiac conduction system terminally differentiated between ED8.5-13.5. These patterns of slowed proliferation correlate well with those in other species, and can serve as a useful marker for the forming conduction system.

Animals↗

PubMed2003

Functional and morphological evidence for a ventricular conduction system in zebrafish and Xenopus hearts.

Zebrafish and Xenopus have become popular model organisms for studying vertebrate development of many organ systems, including the heart. However, it is not clear whether the single ventricular hearts of these species possess any equivalent of the specialized ventricular conduction system found in higher vertebrates. Isolated hearts of adult zebrafish (Danio rerio) and African toads (Xenopus laevis) were stained with voltage-sensitive dye and optically mapped in spontaneous and paced rhythms followed by histological examination focusing on myocardial continuity between the atrium and the ventricle. Spread of the excitation wave through the atria was uniform with average activation times of 20 +/- 2 and 50 +/- 2 ms for zebrafish and Xenopus toads, respectively. After a delay of 47 +/- 8 and 414 +/- 16 ms, the ventricle became activated first in the apical region. Ectopic ventricular activation was propagated significantly more slowly (total ventricular activation times: 24 +/- 3 vs. 14 +/- 2 ms in zebrafish and 74 +/- 14 vs. 35 +/- 9 ms in Xenopus). Although we did not observe any histologically defined tracts of specialized conduction cells within the ventricle, there were trabecular bands with prominent polysialic acid-neural cell adhesion molecule staining forming direct myocardial continuity between the atrioventricular canal and the apex of the ventricle; i.e., the site of the epicardial breakthrough. We thus conclude that these hearts are able to achieve the apex-to-base ventricular activation pattern observed in higher vertebrates in the apparent absence of differentiated conduction fascicles, suggesting that the ventricular trabeculae serve as a functional equivalent of the His-Purkinje system.

Animals↗

PubMed2003

The oldest, toughest cells in the heart.

We review here the evolution and development of the earliest components of the cardiac pacemaking and conduction system (PCS) and the turnover or persistence of such cells into old age in the adult vertebrate heart. Heart rate is paced by upstream foci of cardiac muscle near the future sinoatrial junction even before contraction begins. As the tubular heart loops, directional blood flow is maintained through coordinated sphincter function in the forming atrioventricular (AV) canal and outflow segments. Propagation of initially peristaltoid contraction along and between these segments appears to be influenced by physical conditioning and orientation of inner muscle layers as well as by their slow relaxation; all characteristic of definitive conduction tissue. As classical elements of the mature conduction system emerge, such inner 'contour fibres' maintain muscular and electrical continuity between atrial and ventricular compartments. Elements of such primordial architecture are visible also in histological and optical electrical study of fish and frog hearts. In the maturing chick heart, cells within core conducting tissues retain early thymidine labels from the tubular heart stage into adult life, dividing only slowly, if at all. Preliminary evidence from mammals suggest similar function and kinetics for these 'oldest, toughest' cells in the hearts of all vertebrates.

Aging↗