Robert P Thompson

Publications (28)85.14 Total impact

• Source

  Available from: cuni.cz

  Article: Myocyte proliferation in the developing heart.

  David Sedmera, Robert P Thompson
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  ABSTRACT: Regulation of organ growth is critical during embryogenesis. At the cellular level, mechanisms controlling the size of individual embryonic organs include cell proliferation, differentiation, migration, and attrition through cell death. All these mechanisms play a role in cardiac morphogenesis, but experimental studies have shown that the major determinant of cardiac size during prenatal development is myocyte proliferation. As this proliferative capacity becomes severely restricted after birth, the number of cell divisions that occur during embryogenesis limits the growth potential of the postnatal heart. We summarize here current knowledge concerning regional control of myocyte proliferation as related to cardiac morphogenesis and dysmorphogenesis. There are significant spatial and temporal differences in rates of cell division, peaking during the preseptation period and then gradually decreasing toward birth. Analysis of regional rates of proliferation helps to explain the mechanics of ventricular septation, chamber morphogenesis, and the development of the cardiac conduction system. Proliferation rates are influenced by hemodynamic loading, and transduced by autocrine and paracrine signaling by means of growth factors. Understanding the biological response of the developing heart to such factors and physical forces will further our progress in engineering artificial myocardial tissues for heart repair and designing optimal treatment strategies for congenital heart disease.
  Developmental Dynamics 06/2011; 240(6):1322-34. · 2.54 Impact Factor
• Article: Development of aortic valves with 2 and 3 leaflets.

  Robert H Anderson, Robert P Thompson, Christine B Kern
  Journal of the American College of Cardiology 12/2009; 54(24):2319-20. · 14.16 Impact Factor
• Article: Patterns of muscular strain in the embryonic heart wall.

  Brooke J Damon, Mathieu Rémond, Michael R Bigelow, Thomas C Trusk, Wenjie Xie, Renato Perucchio, David Sedmera, Stewart Denslow, Robert P Thompson
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  ABSTRACT: HH Stage 22 chick heart inflated ex ovo with perfusate containing propidium iodide (red) and 3000 MW dextran (green), viewed here in left sagittal plane by confocal microscopy of acrylamide slab sections. Stretch-sensitive membrane leaks were conspicuous along subendocardial trabeculae near the apex of the looped ventricle (bottom) and along inner wall of AV canal (inset), indicating peak strain of inner wall myocytes as modeled and measured by Damon et al., Developmental Dynamics 238:1535-1546.
  Developmental Dynamics 09/2009; 238(8):spcone. · 2.54 Impact Factor
• Article: Patterns of muscular strain in the embryonic heart wall.

  Brooke J Damon, Mathieu C Rémond, Michael R Bigelow, Thomas C Trusk, Wenjie Xie, Renato Perucchio, David Sedmera, Stewart Denslow, Robert P Thompson
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  ABSTRACT: The hypothesis that inner layers of contracting muscular tubes undergo greater strain than concentric outer layers was tested by numerical modeling and by confocal microscopy of strain within the wall of the early chick heart. We modeled the looped heart as a thin muscular shell surrounding an inner layer of sponge-like trabeculae by two methods: calculation within a two-dimensional three-variable lumped model and simulated expansion of a three-dimensional, four-layer mesh of finite elements. Analysis of both models, and correlative microscopy of chamber dimensions, sarcomere spacing, and membrane leaks, indicate a gradient of strain decreasing across the wall from highest strain along inner layers. Prediction of wall thickening during expansion was confirmed by ultrasonography of beating hearts. Degree of stretch determined by radial position may thus contribute to observed patterns of regional myocardial conditioning and slowed proliferation, as well as to the morphogenesis of ventricular trabeculae and conduction fascicles. Developmental Dynamics 238:1535-1546, 2009. (c) 2009 Wiley-Liss, Inc.
  Developmental Dynamics 06/2009; 238(6):1535-46. · 2.54 Impact Factor
• Chapter: His–Purkinje Lineages and Development

  Robert G. Gourdie, Brett S. Harris, Jacqueline Bond, Angela M. Edmondson, Gang Cheng, David Sedmera, Terrence X. O'Brien, Takashi Mikawa, Robert P. Thompson
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  ABSTRACT: The heartbeat is initiated and coordinated by a multi-component set of specialized muscle tissues collectively referred to as the pacemaking and conduction system. Over the last few years, impetus has gathered into unravelling the cellular and molecular processes that regulate differentiation and integration of this essential cardiac network. One focus of our collective work has been the developmental history of cells comprising His–Purkinje tissues of the conduction system. This interest in part arose from studies of the expression of connexins in periarterial Purkinje fibres of the chick heart. Using lineage-tracing strategies, including those based on replication-defective retroviruses and adenoviruses, it has been shown that conduction cells are derived from multipotent, cardiomyogenic progenitors in the tubular heart. Moreover, heterogeneity within myocardial clones has indicated that the elaboration of the conduction system in the chick embryo occurs by progressive, localized recruitment from within this pool of cardiomyogenic cells. Cell birth dating has revealed that inductive conscription of cells to central elements of the conduction system (e.g. the His bundle) precedes recruitment to the peripheral components of the network (i.e. subendocardial and periarterial Purkinje fibres). Birth dating studies in rodents suggest an analogous recruitment process is occurring in this species. In addition to summarizing earlier work, this chapter provides information on ongoing studies of cell–cell signalling and transcriptional mechanisms that may regulate the development of His–Purkinje tissues.
  10/2008: pages 110 - 124; , ISBN: 9780470868065
• Source

  Available from: Christopher J Drake

  Article: Fibulin-1 is required for morphogenesis of neural crest-derived structures.

  Marion A Cooley, Christine B Kern, Victor M Fresco, Andy Wessels, Robert P Thompson, Tim C McQuinn, Waleed O Twal, Corey H Mjaatvedt, Christopher J Drake, W Scott Argraves
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  ABSTRACT: Here we report that mouse embryos homozygous for a gene trap insertion in the fibulin-1 (Fbln1) gene are deficient in Fbln1 and exhibit cardiac ventricular wall thinning and ventricular septal defects with double outlet right ventricle or overriding aorta. Fbln1 nulls also display anomalies of aortic arch arteries, hypoplasia of the thymus and thyroid, underdeveloped skull bones, malformations of cranial nerves and hemorrhagic blood vessels in the head and neck. The spectrum of malformations is consistent with Fbln1 influencing neural crest cell (NCC)-dependent development of these tissues. This is supported by evidence that Fbln1 expression is associated with streams of cranial NCCs migrating adjacent to rhombomeres 2-7 and that Fbln1-deficient embryos display patterning anomalies of NCCs forming cranial nerves IX and X, which derive from rhombomeres 6 and 7. Additionally, Fbln1-deficient embryos show increased apoptosis in areas populated by NCCs derived from rhombomeres 4, 6 and 7. Based on these findings, it is concluded that Fbln1 is required for the directed migration and survival of cranial NCCs contributing to the development of pharyngeal glands, craniofacial skeleton, cranial nerves, aortic arch arteries, cardiac outflow tract and cephalic blood vessels.
  Developmental Biology 08/2008; 319(2):336-45. · 4.07 Impact Factor
• Article: High-frequency ultrasonographic imaging of avian cardiovascular development.

  Tim C McQuinn, Momka Bratoeva, Angela Dealmeida, Mathieu Remond, Robert P Thompson, David Sedmera
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  ABSTRACT: The chick embryo has long been a favorite model system for morphologic and physiologic studies of the developing heart, largely because of its easy visualization and amenability to experimental manipulations. However, this advantage is diminished after 5 days of incubation, when rapidly growing chorioallantoic membranes reduce visibility of the embryo. Using high-frequency ultrasound, we show that chick embryonic cardiovascular structures can be readily visualized throughout the period of Stages 9-39. At most stages of development, a simple ex ovo culture technique provided the best imaging opportunities. We have measured cardiac and vascular structures, blood flow velocities, and calculated ventricular volumes as early as Stage 11 with values comparable to those previously obtained using video microscopy. The endocardial and myocardial layers of the pre-septated heart are readily seen as well as the acellular layer of the cardiac jelly. Ventricular inflow in the pre-septated heart is biphasic, just as in the mature heart, and is converted to a monophasic (outflow) wave by ventricular contraction. Although blood has soft-tissue density at the ultrasound resolutions and developmental stages examined, its movement allowed easy discrimination of perfused vascular structures throughout the embryo. The utility of such imaging was demonstrated by documenting changes in blood flow patterns after experimental conotruncal banding.
  Developmental Dynamics 01/2008; 236(12):3503-13. · 2.54 Impact Factor
• Article: Versican proteolysis mediates myocardial regression during outflow tract development.

  Christine B Kern, Russell A Norris, Robert P Thompson, W Scott Argraves, Sarah E Fairey, Leticia Reyes, Stanley Hoffman, Roger R Markwald, Corey H Mjaatvedt
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  ABSTRACT: An important phase of cardiac outflow tract (OFT) formation is the remodeling of the distal region of the common outlet in which the myocardial sleeve is replaced by with smooth muscle. Here we demonstrate that expression of the proteoglycan versican is reduced before the loss of myocardium from the distal cardiac outlet concomitant with an increase in production of the N-terminal cleavage fragment of versican. To test whether versican proteolysis plays a role in OFT remodeling, we determined the effects of adenoviral-mediated expression of a versican isoform devoid of known matrix metalloproteinase cleavage sites (V3) and an N-terminal fragment of versican (G1). V3 expression promoted an increase in thickness of the proximal OFT myocardial layer independent of proliferation. In contrast, the G1 domain caused thinning and interruptions of the OFT myocardium. These in vivo findings were consistent with findings using cultured primary cardiomyocytes showing that the V3 promoted myocardial cell-cell association while the G1 domain caused a loss of myocardial cell-cell association. Taken together, we conclude that intact versican and G1-containing versican cleavage products have opposing effects on myocardial cells and that versican proteolysis may facilitate the loss of distal myocardium during OFT remodeling.
  Developmental Dynamics 04/2007; 236(3):671-83. · 2.54 Impact Factor
• Article: Changes in activation sequence of embryonic chick atria correlate with developing myocardial architecture.

  David Sedmera, Andy Wessels, Thomas C Trusk, Robert P Thompson, Kenneth W Hewett, Robert G Gourdie
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  ABSTRACT: To characterize developmental changes in impulse propagation within atrial musculature, we performed high-speed optical mapping of activation sequence of the developing chick atria using voltage-sensitive dye. The activation maps were correlated with detailed morphological studies using scanning electron microscopy, histology, and whole mount confocal imaging with three-dimensional reconstruction. A preferential pathway appeared during development within the roof of the atria, transmitting the impulse rapidly from the right-sided sinoatrial node to the left atrium. The morphological substrate of this pathway, the bundle of Bachman, apparent from stage 29 onward, was a prominent ridge of pectinate muscles continuous with the terminal crest. Further acceleration of impulse propagation was noted along the ridges formed by the developing pectinate muscles, ramifying from the terminal crest toward the atrioventricular groove. In contrast, when the impulse reached the interatrial septum, slowing was often observed, suggesting that the septum acts as a barrier or sink for electrical current. We conclude that these inhomogeneities in atrial impulse propagation are consistent with existence of a specialized network of fast-conducting tissues. The purpose of these preferential pathways appears to be to assure synchronous atrial activation and contraction rather than rapid impulse conduction between the sinoatrial and atrioventricular nodes.
  AJP Heart and Circulatory Physiology 11/2006; 291(4):H1646-52. · 3.71 Impact Factor
• Chapter: Topological Segmentation and Smoothing of Discrete Curve Skeletons

  Wenjie Xie, Renato Perucchio, David Sedmera, Robert P. Thompson
  12/2005: pages 389 - 409; , ISBN: 9780470094167
• Article: Confocal imaging of the embryonic heart: how deep?

  Christine E Miller, Robert P Thompson, Michael R Bigelow, George Gittinger, Thomas C Trusk, David Sedmera
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  ABSTRACT: Confocal microscopy allows for optical sectioning of tissues, thus obviating the need for physical sectioning and subsequent registration to obtain a three-dimensional representation of tissue architecture. However, practicalities such as tissue opacity, light penetration, and detector sensitivity have usually limited the available depth of imaging to 200 microm. With the emergence of newer, more powerful systems, we attempted to push these limits to those dictated by the working distance of the objective. We used whole-mount immunohistochemical staining followed by clearing with benzyl alcohol-benzyl benzoate (BABB) to visualize three-dimensional myocardial architecture. Confocal imaging of entire chick embryonic hearts up to a depth of 1.5 mm with voxel dimensions of 3 microm was achieved with a 10x dry objective. For the purpose of screening for congenital heart defects, we used endocardial painting with fluorescently labeled poly-L-lysine and imaged BABB-cleared hearts with a 5x objective up to a depth of 2 mm. Two-photon imaging of whole-mount specimens stained with Hoechst nuclear dye produced clear images all the way through stage 29 hearts without significant signal attenuation. Thus, currently available systems allow confocal imaging of fixed samples to previously unattainable depths, the current limiting factors being objective working distance, antibody penetration, specimen autofluorescence, and incomplete clearing.
  Microscopy and Microanalysis 07/2005; 11(3):216-23. · 3.01 Impact Factor
• Article: Optical mapping of electrical activation in the developing heart.

  David Sedmera, Maria Reckova, Carlin Rosengarten, Maria I Torres, Robert G Gourdie, Robert P Thompson
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  ABSTRACT: 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.
  Microscopy and Microanalysis 07/2005; 11(3):209-15. · 3.01 Impact Factor
• Article: Developmental transitions in electrical activation patterns in chick embryonic heart.

  David Sedmera, Maria Reckova, Michael R Bigelow, Angela Dealmeida, Chiffvon P Stanley, Takashi Mikawa, Robert G Gourdie, Robert P Thompson
  [show abstract] [hide abstract]
  ABSTRACT: 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.
  The Anatomical Record Part A Discoveries in Molecular Cellular and Evolutionary Biology 11/2004; 280(2):1001-9.
• Article: Effects of deletion of the tissue inhibitor of matrix metalloproteinases-1 gene on the progression of murine thoracic aortic aneurysms.

  John S Ikonomidis, William C Gibson, Jessica E Butler, David M McClister, Sarah E Sweterlitsch, Robert P Thompson, Rupak Mukherjee, Francis G Spinale
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  ABSTRACT: The cause of thoracic aortic aneurysms (TAAs) is poorly understood. Previous work has suggested an association between development of aortic aneurysms and matrix metalloproteinase (MMP) activity. We hypothesized that removal of the primary endogenous aortic MMP inhibitor (TIMP) through TIMP-1 gene deletion will increase TAA progression. The descending thoracic aortas of wild-type 129 SvE and TIMP-1 gene knockout (TIMP-1-/-) mice were exposed to 0.5 mol/L CaCl2 for 15 minutes, with terminal studies performed at 4 or 8 weeks. TAA lumen diameter was measured using confocal microscopy and normalized to the ascending aorta. In addition, sections were studied with in situ zymography and immunohistochemistry staining for MMP-9. Both wild-type [TAA/ascending ratio (mean+/-SEM): control, 0.85+/-0.02 (n=14); 4 weeks, 1.00+/-0.03 (n=13); 8 weeks, 1.05+/-0.10 (n=9)] and TIMP-1-/- [control, 0.98+/-0.04 (n=11); 4 weeks, 1.10+/-0.03 (n =21); 8 weeks, 1.22+/-0.09 (n=10)] groups developed aneurysms at 4 and 8 weeks compared with their respective controls (P<0.05). TIMP-1-/- animals developed larger aneurysms than the corresponding wild-type group (P<0.05). Aneurysms in the TIMP-1-/- group were larger at 8 weeks than at 4 weeks (P<0.05), which was not seen in the wild-type aneurysm groups. Both groups showed presence of MMP-9 in 4 and 8 weeks, most prominently in the adventitia and outer media. In situ zymographic activity was increased in the 8-week TIMP-1-/- group compared with wild-type. Deletion of the TIMP-1 gene results in increased and continued progression of aneurysm formation compared with wild-type mice in a unique TAA model caused at least in part by an alteration in the balance between gelatinase activity and its endogenous inhibition. Therapeutic strategies aimed at modifying MMP activity may reduce or prevent the progression of TAAs.
  Circulation 09/2004; 110(11 Suppl 1):II268-73. · 14.74 Impact Factor
• Article: Optical Mapping of Electrical Activation in Developing Heart

  David  Sedmera , Carlin I.  Rosengarten , Robert G.  Gourdie , Robert P.  Thompson 
  Microscopy and Microanalysis 07/2004; 10:198 - 199. · 3.01 Impact Factor
• Article: A murine model of thoracic aortic aneurysms.

  John S Ikonomidis, William C Gibson, Jonathan Gardner, Sarah Sweterlitsch, Robert P Thompson, Rupak Mukherjee, Francis G Spinale
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  ABSTRACT: The mechanisms of thoracic aortic aneurysm (TAA) formation are poorly understood, mainly due to the lack of a useful and reproducible model. Accordingly, the goal of this study was to test the hypothesis that abluminal calcium chloride (CaCl(2)) application could create TAAs in the mouse. Adult 129/SvE mice (n = 8) were anesthetized and their thoracic aortas exposed via left thoracotomy. CaCl(2) (0.5M) was applied to the distal descending thoracic aorta for 15 min followed by chest closure. At 4 weeks, the perfusion-fixed aorta was harvested from the root to the renal arteries. Diameter measurements were made using confocal microscopy, and wall thickness was measured from hematoxylin and eosin-stained sections. The control (n = 15) distal descending thoracic aortic diameter was 0.60 +/- 0.04 mm and increased by 25% (0.76 +/- 0.06 mm, P < 0.05) following CaCl(2) treatment. Control aortic wall thickness was 48 +/- 9 mum and decreased by 47% in corresponding CaCl(2)-exposed segments (25 +/- 8 mum, P < 0.05). The diameter and wall thickness of the ascending aorta (used as an internal control) were not significantly different between groups. Picrosirius red staining of the TAA showed adventitial collagen breakdown and disruption of lamellar organization. We conclude that abluminal application of CaCl(2) to the thoracic aorta reliably produces dilation, wall-thinning, and disruption of mural architecture, the hallmark signs of aneurysm formation. To our knowledge, these findings describe for the first time the generation of a reproducible model of isolated TAA formation in a murine system.
  Journal of Surgical Research 11/2003; 115(1):157-63. · 2.25 Impact Factor
• Article: Spatiotemporal pattern of commitment to slowed proliferation in the embryonic mouse heart indicates progressive differentiation of the cardiac conduction system.

  David Sedmera, Maria Reckova, Angela DeAlmeida, Steven R Coppen, Steven W Kubalak, Robert G Gourdie, Robert P Thompson
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  ABSTRACT: 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.
  The Anatomical Record Part A Discoveries in Molecular Cellular and Evolutionary Biology 10/2003; 274(1):773-7.
• Article: Heart development in the spotted dolphin (Stenella attenuata).

  David Sedmera, Ivan Misek, Milan Klima, Robert P Thompson
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  ABSTRACT: Marine mammals show many deviations from typical mammalian characteristics due to their high degree of specialization to the aquatic environment. In Cetaceans, some of the features of limbs and dentition resemble very ancestral patterns. In some species, hearts with a clearly bifid apex (a feature normally present during mammalian embryogenesis prior to completion of ventricular septation) have been described. However, there is a scant amount of data regarding heart development in Cetaceans, and it is not clear whether the bifid apex is the rule or the exception. We examined samples from a unique collection of embryonic dolphin specimens macroscopically and histologically to learn more about normal cardiac development in the spotted dolphin. It was found that during the dolphin's 280 days of gestation, the heart completes septation at about 35 days. However, substantial trabecular compaction, which normally occurs in chicks, mice, and humans at around that time period, was delayed until day 60, when coronary circulation became established. At that time, the apex still appeared bifid, similarly to early fetal mouse or rat hearts. By day 80, however, the heart gained a compacted, characteristic shape, with a single apex. It thus appears that the bifid apex in the adult Cetacean heart is probably particular to certain species, and its significance remains unclear.
  The Anatomical Record Part A Discoveries in Molecular Cellular and Evolutionary Biology 09/2003; 273(2):687-99.
• Source

  Available from: gva.es

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

  Maria Reckova, Carlin Rosengarten, Angela deAlmeida, Chiffvon P Stanley, Andy Wessels, Robert G Gourdie, Robert P Thompson, David Sedmera
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  ABSTRACT: 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.
  Circulation Research 08/2003; 93(1):77-85. · 9.49 Impact Factor
• Article: Functional and morphological evidence for a ventricular conduction system in zebrafish and Xenopus hearts.

  David Sedmera, Maria Reckova, Angela deAlmeida, Martina Sedmerova, Martin Biermann, Jiri Volejnik, Alexandre Sarre, Eric Raddatz, Robert A McCarthy, Robert G Gourdie, Robert P Thompson
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  ABSTRACT: 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.
  AJP Heart and Circulatory Physiology 05/2003; 284(4):H1152-60. · 3.71 Impact Factor