The mammalian ventricular myocardium forms a functional syncytium due to flow of electrical current mediated in part by gap junctions localized within intercalated disks. The connexin (Cx) subunit of gap junctions have direct and indirect roles in conduction of electrical impulse from the cardiac pacemaker via the cardiac conduction system (CCS) to working myocytes. Cx43 is the dominant isoform in these channels. We have studied the distribution of Cx43 junctions between the CCS and working myocytes in a transgenic mouse model, which had the His-Purkinje portion of the CCS labeled with green fluorescence protein. The highest number of such connections was found in a region about one-third of ventricular length above the apex, and it correlated with the peak proportion of Purkinje fibers (PFs) to the ventricular myocardium. At this location, on the septal surface of the left ventricle, the insulated left bundle branch split into the uninsulated network of PFs that continued to the free wall anteriorly and posteriorly. The second peak of PF abundance was present in the ventricular apex. Epicardial activation maps correspondingly placed the site of the first activation in the apical region, while some hearts presented more highly located breakthrough sites. Taken together, these results increase our understanding of the physiological pattern of ventricular activation and its morphological underpinning through detailed CCS anatomy and distribution of its gap junctional coupling to the working myocardium.

• Klíčová slova
• cardiac conduction system, connexin, immunohistochemistry, myocardium, optical mapping,
• MeSH
• konexin 43 fyziologie   MeSH
• mezerový spoj fyziologie   MeSH
• mezibuněčná komunikace * MeSH
• myši MeSH
• perikard cytologie   fyziologie   MeSH
• Purkyňova vlákna cytologie   fyziologie   MeSH
• srdeční komory patologie   MeSH
• svalové buňky cytologie   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• GJA1 protein, mouse MeSH Prohlížeč
• konexin 43 MeSH

Most embryonic ventricular cardiomyocytes are quite uniform, in contrast to the adult heart, where the specialized ventricular conduction system is molecularly and functionally distinct from the working myocardium. We thus hypothesized that the preferential conduction pathway within the embryonic ventricle could be dictated by trabecular geometry. Mouse embryonic hearts of the Nkx2.5:eGFP strain between ED9.5 and ED14.5 were cleared and imaged whole mount by confocal microscopy, and reconstructed in 3D at 3.4 μm isotropic voxel size. The local orientation of the trabeculae, responsible for the anisotropic spreading of the signal, was characterized using spatially homogenized tensors (3 × 3 matrices) calculated from the trabecular skeleton. Activation maps were simulated assuming constant speed of spreading along the trabeculae. The results were compared with experimentally obtained epicardial activation maps generated by optical mapping with a voltage-sensitive dye. Simulated impulse propagation starting from the top of interventricular septum revealed the first epicardial breakthrough at the interventricular grove, similar to experimentally obtained activation maps. Likewise, ectopic activation from the left ventricular base perpendicular to dominant trabecular orientation resulted in isotropic and slower impulse spreading on the ventricular surface in both simulated and experimental conditions. We conclude that in the embryonic pre-septation heart, the geometry of the A-V connections and trabecular network is sufficient to explain impulse propagation and ventricular activation patterns.

• Klíčová slova
• cardiac conduction, mathematical modeling, mouse embryo, optical mapping, trabeculation,
• Publikační typ
• časopisecké články MeSH

The left and right ventricle originate from distinct parts of the cardiac tube, and several genes are known to be differentially expressed in these compartments. The aims of this study were to determine developmental differences in gene expression between the left and right ventricle, and to assess the effect of altered hemodynamic loading. RNA was extracted from isolated left and right normal chick embryonic ventricles at embryonic day 6, 8, and 10, and from day 8 left atrial ligated hearts with hypoplastic left and dilated right ventricles. cRNA was hybridized to Affymetrix Chicken Genome array according to manufacturer protocols. Microarray analysis identified 302 transcripts that were differentially expressed between the left and right ventricle. Comparative analysis detected 91 genes that were different in left ventricles of ligated hearts compared to age-matched ventricles, while 66 were different in the right ones. A large number of the changes could be interpreted as a delay of normal maturation. The approach described in this study could be used as one of the measures to gauge success of surgical procedures for congenital heart disease and help in determining the optimal time frame for intervention to prevent onset of irreversible changes.

• MeSH
• hemodynamika MeSH
• kuřecí embryo MeSH
• mikročipová analýza MeSH
• myokard metabolismus   MeSH
• srdeční komory embryologie   metabolismus   MeSH
• srdeční síně embryologie   metabolismus   MeSH
• transkriptom MeSH
• zvířata MeSH
• Check Tag
• kuřecí embryo MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

The phylogeny of the heart and its conducting system is surveyed in the present study, as well as its parallels with ontogeny. A concise review of its evolution in the main taxonomic groups is presented. The aim is to inform physicians on evolutionary connections to the physiology of the human heart conducting system. Furthermore, some unanswered questions in terms of the developmental biology of the heart are offered. It is assumed that some supraventricular arrhythmias are based on remnants of embryonic structures of the pacemaking or conducting tissues; atrial flutter could re-entry through a survived embryonic sinoatrial ring. Some cases of atrial fibrillation could be initiated from remnant embryonic pacemaking cells settled in pulmonary veins.

• Klíčová slova
• Animals, Arrhythmia, Comparative anatomy, Heart, Heart conducting system, Humans, Ontogeny, Phylogeny,
• Publikační typ
• časopisecké články MeSH