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Skeletal muscle-specific myosin binding protein-H is expressed in Purkinje fibers of the cardiac conduction system.

Heart contraction is coordinated by conduction of electrical excitation through specialized tissues of the cardiac conduction system. By retroviral single-cell tagging and lineage analyses in the embryonic chicken heart, we have recently demonstrated that a subset of cardiac muscle cells terminally differentiates as cells of the peripheral conduction system (Purkinje fibers) and that this occurs invariably in perivascular regions of developing coronary arteries. Cis regulatory elements that function in transcriptional regulation of cells in the conducting system have been distinguished from those in contractile cardiac muscle cells; eg, 5' regulatory sequences of the desmin gene act as enhancer elements in skeletal muscle and in the conduction system but not in cardiac muscle. We hypothesize that Purkinje fiber differentiation involves a switch of the gene expression program from that characteristic of cardiac muscle to one typical of skeletal muscle. To test this hypothesis, we examined the expression of myosin binding protein-H (MyBP-H) in Purkinje fibers of chicken hearts. This unique myosin binding protein is present in skeletal but not cardiac myocytes. A site-directed polyclonal antibody (AB105) was generated against MyBP-H. Immunohistological analysis of the myocardium mapped the AB105 antigen predominantly to A bands of myofibrils within Purkinje fibers. Western blot analysis of whole extracts from the ventricular wall of adult chicken hearts revealed that the AB105 epitope was restricted to a single protein of approximately 86 kD, the same size as MyBP-H in skeletal muscle. Biochemical properties of the Purkinje fiber 86-kD protein and RNase protection analyses of its mRNA indicate that Purkinje fiber 86-kD protein is indistinguishable from skeletal muscle MyBP-H. The results provide evidence that skeletal muscle MyBP-H is expressed in a subset of cardiac muscle cells that differentiate into Purkinje fibers of the heart.

Animals↗

Biochemical studies on energy metabolism in the conduction system of bovine heart.

The conduction system of bovine heart was studied to clarify the characteristics of its energy metabolism. Results showed that its mitochondrial oxygen uptake was much lower than that of ordinary heart muscle with succinate as substrate but similar to that of ordinary heart muscle with glutamate + malate as substrate. The activity of succinate dehydrogenase was lower than that in ordinary heart muscle. The total activity of isozymes of lactate dehydrogenase was lower in the specialized heart muscle than in ordinary heart muscle. The main isozyme of lactate dehydrogenase in the specialized heart muscle was LDH 1 (H4). The cytoplasmic NAD+/NADH ratio as much higher in the specialized heart muscle than in ordinary heart muscle. These results suggest that in the specialized heart muscle energy is mainly derived from aerobic metabolism.

Animals↗

Structure and distribution of lymphatic capillaries and fenestrated blood capillaries in the conduction system of the rabbit heart.

The distribution and structure of lymphatic and blood capillaries in the rabbit heart conduction system were investigated by transmission electron microscopy. The sinuatrial node, atrioventricular node, and atrioventricular bundle possessed a rich network of lymphatic capillaries, which were situated not only at the periphery but also in the interior of the conduction system. The fine structure of these lymphatic capillaries was essentially similar to those within the atria and the ventricles. Although blood capillaries within working myocardium were nonfenestrated, the heart conduction system was often supplied by fenestrated blood capillaries. In the atrioventricular node and bundle especially, fenestrated blood capillaries and lymphatic capillaries were topographically associated, forming an extensive microcirculatory system. The presence of fenestrated capillaries suggests that a fast transcapillary passage of metabolites occurs in these regions, while the lymphatic capillaries may play an important role in the removal of macromolecules and excess intercellular fluid.

Animals↗

Electrophysiologic effects of blocking and stimulating the opioid system in patients with unexplained heart palpitations.

The opioid system plays a role in the regulation of the cardiovascular system. Endogenic as well as egzogenic administration of opioids influences the heart rhythm. This work was undertaken in order to assess the influence of crossover activity of the heart opioid system on the heart conduction system in patients with various disturbances of rhythm having an efficient circulatory system and a normal 12-lead stationary ECG. Subjects were 20 patients (9 men and 11 women of mean age of 38.7 years) reporting sudden heart palpitations. They were subjected to invasive programmable electrophysiological studies (PES). Naloxone was administered intravenously to 10 patients. Pentazocine was administered in the same way. In the remaining 10 patients the order of drug administration was reversed. PES was done in the basic state and after the administration of each drug. Study results were subjected to statistical analysis with no-parameter Wilcoxon test assuming differences to be significant at p less than 0.05. Blocking of the opioid system resulted in significant lengthening of the sinoatrial (SACT), intra-atrial (PA), and atrioventricular node (AH) conduction times, while no changes were induced in conduction in the His-Purkinje system (HV) and automation of the sinus node. Naloxone lengthened the atrial (ERPA) and atrioventricular node (ERPA AVN) effective refractory periods. Stimulation of the opioid system resulted in decreases of the following values: SACT, PA, AH, ERPA, ERPA AVN, while no effect was exerted on the SNRT, HV, ERPV. Neither drug influenced the QRS time, although naloxone lengthened QTc period significantly. Opioids did not influence the time of conduction in concealed extranodal atrioventricular pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗

Development of the conduction system in the rat heart as determined by Leu-7 (HNK-1) immunohistochemistry and computer graphics reconstruction.

BACKGROUND: The development of the heart conduction system is controversial. Our previous study demonstrated anti-Leu-7 antibody to cross-react with the cells of the conduction system in the embryonic rat heart. Thus, detailed analysis of the development of the conduction system was performed by immunohistochemical reaction with the use of the antibody. DESIGN: Horizontal serial sections of hearts obtained from embryonic and neonatal rats were treated for immunohistochemical reaction with anti-Leu-7 antibody, and three-dimensional images were reconstructed by computer graphics. Images were analyzed by superimposing the results on scanning electron micrographs. RESULTS: The development of the rat heart conduction system starts at 10 days and is completed by 18 days of gestation. The presence of three internodal tracts (INT1, -2, and -3) and two primordia of the atrioventricular node were confirmed in this process. INT1 and -3 pass through the septum spurium. INT2 follows the same route as the posterior internodal tract of James, but the other two INTs showed no correlation to previously described tracts. The sinuatrial node and INTs were found to be derivatives of the so-called S-A ring, and the bundle of His and bundle branches were found to be derived from the B-V ring. In this study, no immunoreactivity was observed in cells of the truncobulbar portion. CONCLUSIONS: Three internodal tracts and two atrioventricular node primordia were observed in the developing heart. The paths of the three internodal tracts showed intimate relationships with the internal structures of the heart. The developmental significance of the septum spurium, sinus septum, and venous valve was discussed.

Animals↗

Gangliosides of the bovine heart impulse conducting system.

The ganglioside analysis of the heart impulse conducting system was carried out, comparing it with that of ordinary myocardium. The heart impulse conducting system contained about 3-times more gangliosides than ordinary myocardium and showed a distinctly different ganglioside composition. These observations seemed to indicate that the differentiation between myoblasts and each type of cardiac muscle cell, impulse conducting system and ordinary myocardium cells, resulted in their characteristic ganglioside compositions.

Animals↗

A morphologic study on human conduction system of heart considering influences of some disorders of individuals.

The authors have investigated the aging changes of the human AV node, AV bundle, and bundle branches considering the influences of various disorders of individuals upon these conduction tissues. These conduction tissues began to develop gradually from the infant stage and the development was completed by young adult stage. Aging changes of the conduction tissues were fat infiltration, fibrosis and elastosis, disappearance of muscle fiber, and general atrophy of the conduction tissues. They were thought to occur not only by aging but also by the influences of various disorders particularly of long-standing chronic diseases. Changes of the conduction tissues seem to be related with thickening and luminal narrowing of the AV nodal artery and superior ventricular septal arteries. Marked elastosis or atrophy was noted in the cases suffering from some long-standing disorder regardless of the sort of disorders. In the cases which were diagnosed as complete heart block clinically, destruction of the conduction tissues was extremely severe including those of the SA node.

Adolescent↗

The distribution of nerve fibers showing substance P-like immunoreactivity in the conduction system of the bovine heart: dense innervation in the atrioventricular bundle.

There is limited information on the distribution of nerve fibers containing substance P (SP) in the heart conduction system. Therefore, in the present study, the various parts of the conduction system of the bovine heart were examined by the use of an SP-antiserum and immunohistochemistry. Nerve fibers showing SP-like immunoreactivity (SP-LI) occurred in the proximities of conduction cells in all parts of the conduction system, but were present in greatly larger numbers in the AV bundle than in the other parts. The nerve fibers showed a predilection for certain regions of the bundles of conduction cells (Purkinje fiber bundles) in the AV bundle and the bundle branches and their ramifications. Nerve fibers showing SP-LI also occurred in the walls of the arteries and in association with some the ganglionic cells located in the regions of the conduction system. None of the ganglionic cells exhibited SP-LI. The observations are discussed in relation to what is known of the function of SP in the heart and of the distribution of sympathetic and parasympathetic nerve fibers in the conduction system. As SP is regarded as a marker of afferent fibers the observations support the view that afferent nerve fibers are present throughout the conduction system. It is likely that the existence of a significant SP-innervation in the conduction system is of importance for the function of this part of the heart.

Afferent Pathways↗

Atrioventricular conduction system in hearts with muscular ventricular septal defects in the setting of complete transposition.

The detailed structure of a ventricular septal defect was compared in 90 hearts with complete transposition (concordant atrioventricular and discordant ventriculoarterial connections) and in 102 hearts with concordant connections at both junctions; the latter group was selected to include only cases with the septums aligned in the normal way. The interventricular communications observed in 13% of the group with complete transposition, which, in our material, had no counterpart in the hearts with concordant segmental connections, were of special interest. These defects, completely surrounded by muscle, were positioned around the midline on the right side of the septum but always lay under or partially under the septal leaflet of the tricuspid valve. The medial papillary muscle group was always to the "left hand margin" of the defect as seen by the surgeon. Because these defects lay within the boundaries set by the septal leaflet of the tricuspid valve, they would conform to the criteria for classification as inlet muscular defects but could equally be described as central or subtricuspid. It is significant that, in all those cases with histologic sectioning, the axis of atrioventricular conduction tissue ran to the surgeon's right hand margin. This position is markedly different from the pattern found in typical defects of the inlet septum, which are completely surrounded by muscle and extend to the posterior wall of the heart. In this more common situation, the conduction axis runs above the left hand margin of the defect. This finding has obvious implications for surgical treatment.

Heart Conduction System↗

[LDH isoenzyme spectrum of the extramural ganglia of the autonomic nervous system, the working heart, and cardiac conduction system of rabbits during acute experimental emotional stress].

The content of LDH isozymes was studied in extramural ganglions (superior cervical ganglion, stellate ganglion and symphathetic chain at the level of the 4th--6th thoracic segments) of the sympathetic nervous system, of the nodosal ganglion of the vagus nerve, working myocardium and conductive system of the heart of rabbits with acute experimental emotional stress provoked by simultaneous electric stimulation of the negative emotiogenic area of the hypothalamus, ventromedial nuclei, and skin. Under conditions of emotional stress no changes could be recorded in the ratio of LDH isozymic fractions in the ganglions as compared with control. No changes were found in LDH content of the working myocardium in rabbits exposed to stress. The conductive system of the heart (atrioventricular node and His' bundle) demonstrated a certain sensitivity to stress, manifesting in the increased activity of fast-moving fractions in the spectrum of LDH isozymes. The modulated electromagnetic field that exerts a protective action against an adverse effect of emotional stress produced significant shifts in LDH spectrum in the ganglions of the autonomous nervous system. No changes were detected in the spectrum of LDH isozymes in the conductive system. The results obtained suggest that the above structures of the autonomous nervous system are an important link in the bodily response to the concomitant action of the two stressors.

Acute Disease↗

Subcellular redistribution of la/SSB autoantigen during physiologic apoptosis in the fetal mouse heart and conduction system: a clue to the pathogenesis of congenital heart block.

OBJECTIVE: In isolated congenital heart block, the mechanism by which maternal autoantibodies target the intracellular components of the Ro/La RNP complex is unclear. Previous studies have demonstrated that cultured fetal cardiac myocytes rendered apoptotic bind antibodies to 48-kd La/SSB. This study further investigated the subcellular distribution of the La antigen during apoptosis in the fetal mouse heart and conduction system. METHODS: The atrioventricular (AV) node, AV bundle, and sinoatrial (SA) node were identified in serial sections prepared from paraffin blocks of normal mouse fetuses on days 15, 17, and 19 of gestation. Apoptosis was detected by TUNEL assay. Under confocal microscopy, fluorescent labeling of fragmented DNA in apoptotic cells was assessed by TUNEL, and La protein localization was visualized simultaneously using a murine monoclonal antibody or affinity-purified human polyclonal anti-La antibodies. RESULTS: Apoptotic cells were detected in and at the periphery of the AV and SA nodes as well as in the fetal heart valve insertions and working myocardium. In contrast, no apoptosis was detected in the adult heart AV node or surrounding myocardium. As expected, the La antigen was predominantly immunolocalized to the nucleus in nonapoptotic cells. However, apoptotic cells showed a marked reduction of nuclear La and redistribution of La to the cytoplasm. High-resolution confocal microscopy revealed that in cells that had undergone apoptosis, La antigen asymmetrically clustered near the surface of TUNEL-positive nuclei and apoptotic bodies. CONCLUSION: These data provide the first in vivo demonstration of the subcellular translocation of La autoantigen during apoptosis in the fetal heart and the conduction system under physiologic conditions. This observation supports the hypothesis that subcellular redistribution of La in the normally developing heart facilitates the binding of cognate maternal antibodies and subsequent tissue damage.

Animals↗