Sinus and atrioventricular nodal distribution of sympathetic fibers that contain neuropeptide Y.

Neuropeptide Y and norepinephrine are localized in sympathetic nerve terminals throughout the heart. We sought to determine the functional distribution of the neuropeptide Y-containing sympathetic fibers to the sinus and atrioventricular (AV) nodal regions. We recorded cycle length, AV interval, and arterial pressure in 14 anesthetized dogs. We assessed the release of neuropeptide Y from sympathetic nerve terminals by measuring the attenuation of the vagal effects on cycle length and AV interval that occurred after unilateral ansa subclavia stimulation. Three-minute trains of right or left ansa stimulation, each applied at frequencies of 2, 5, and 10 Hz, produced a frequency-dependent inhibition of the vagal effects on cycle length and AV interval. After right ansa stimulation (10 Hz), however, the percent inhibition of the vagal effects on cycle length was 21 +/- 5% greater (p less than 0.001) than the percent inhibition of the vagal effects on AV interval. Conversely, after left ansa stimulation (10 Hz), the percent inhibition of the vagal effects on AV interval was 54 +/- 7% greater (p less than 0.001) than the percent inhibition of the vagal effects on cycle length. The vagal stimulus characteristics (frequency or voltage) did not significantly alter the percent inhibition, nor did the percent inhibition depend on the vagus stimulated (right or left vagus). We conclude that most of the neuropeptide Y-containing sympathetic fibers at the sinus node originate in right-sided ganglia, whereas most of those at the AV node originate in left-sided ganglia.

Densitometric analysis of beta 1- and beta 2-adrenoceptors in guinea-pig atrioventricular conducting system.

Quantitative autoradiography was used to determine the densities of beta 1- and beta 2-adrenoceptors in the atrioventricular conducting system in guinea-pig. (-)[125I]Cyanopindolol (CYP) was used to label beta 1- and beta 2-adrenoceptors in the absence or presence of the beta 1-adrenoceptor selective antagonist CGP 20712A (100 nM) or the beta 2-adrenoceptor selective antagonist ICI 118,551 (70 nM) or the non-selective beta-adrenoceptor antagonist (-)-propranolol (1 microM). Protein in discrete anatomical regions was determined using a densitometric method based on the dye Coomassie brilliant blue G. In the atrioventricular conducting system the proportion of beta 2-adrenoceptors determined by inhibition of total (-)[125I]-CYP binding by CGP 20712A (100 nM) ranged from 32.5% (atrioventricular node) to 48.7% (left bundle branch). In the atrioventricular node (16.8 fmol/mg protein), bundle of His (12.1 fmol/mg protein), right (17.4 fmol/mg protein) and left (21.1 fmol/mg protein) bundle branches and Purkinje cells there was a higher density of beta 2-adrenoceptors than in the interventricular septum (8.4 fmol/mg protein) and right atria (8.3 fmol/mg protein). The medial smooth muscle of the aorta, aortic valve, adventitia of the aorta, nerve tissue, tricuspid and mitral valves contained only beta 2-adrenoceptors. It is speculated that the use of beta-adrenoceptor antagonists to control cardiac arrhythmias involving a defect in conduction in the atrioventricular node should take into consideration both beta 1- and beta 2-adrenoceptors.

Distribution and metabolism of norepinephrine, cyclic AMP and cyclic GMP in the atrioventricular conducting tissue of the bovine heart.

The distribution of norepinephrine (NE), cyclic AMP (cAMP) and cyclic GMP (cGMP) and the activities of related enzymes in the atrioventricular (A-V) conducting tissue of the bovine heart were examined. The concentration of NE in the atrium was about twice that in the ventricle. In the A-V conducting tissue, the concentration of NE was highest in the atrioventricular node (AVN) and lowest in the false tendon (FT), with intermediate levels in the bundle of His (HIS) and the right and left bundle branches (RLBB). The activity of monoamine oxidase (MAO) in the atrium was about 2.2 times that in the ventricle. In the A-V conducting tissue, the activity of MAO was highest in the HIS and lowest in the FT. The activity of catechol-o-methyltransferase (COMT) in the atrium and ventricle was similar, and that in the HIS was slightly, but not significantly, higher than that in other regions of the A-V conducting tissue. The concentration of cAMP in the ventricle was about twice that in the atrium. In the A-V conducting tissue, the concentration of cAMP was higher in the AVN and FT than in the HIS and RLBB. The distribution of adenylate cyclase (AC) was similar to that of NE. The phosphodiesterase (PDE) activity in the atrium and ventricle was similar. No significant difference was found in the level of PDE activity in different regions of the A-V conducting tissue. The concentration of cGMP was slightly, but not significantly, higher in the A-V conducting tissue than in the atrium or ventricle. In the A-V conducting tissue, the concentration of cGMP was highest in the FT and the concentrations in the HIS, RLBB and AVN were similar. These findings suggest that in the A-V conduction tissue, the regions that have the higher spontaneous pacemaker rates have higher NE content and AC activity, that is sensitivity to NE. Furthermore, the sensitivity for muscarinic cholinergic stimulation is higher in the conducting tissue (especially in the FT) than in the atrium and ventricle.

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.

The atrioventricular node of the golden hamster (Mesocricetus auratus): a light and electron microscopic study including immunocytochemistry.

The atrioventricular (AV) node of the golden hamster is situated unusually high in the interatrial septum when compared to other species such as the rat. 2 main cell types, characterized by electron-lucent or electron-dense cytoplasm respectively, are found in the node; although both types contain numerous myofilaments these are irregularly arranged and sarcomeric banding is poor. A third variety comparising transitional cells, with features intermediate between the main nodal cells and general atrial myocardial cells, are found at the periphery of the node. Similar electron-lucent and electron-dense cells are also found in the bundle and the mean diameter of bundle cells increases as one passes from the node to the bundle bifurcation. In the node, specific heart granules (SHG) identified by ANP-28 immunoreactivity are found only in transitional cells and even here they are very sparse, unlike general atrial myocytes in which they are plentiful. Numerous nerve varicosities are present throughout the node and bundle and 5-hydroxydopamine (5-OHDA) labelling demonstrates that most of them have features of either noradrenergic or cholinergic terminals; a few non-cholinergic, non-adrenergic varicosities are also present.

Characterization of beta 1- and beta 2-adrenoceptor subtypes in the rat atrioventricular node by quantitative autoradiography.

We characterized beta-adrenoceptor subtypes in the atrioventricular node of the rat heart by quantitative autoradiography. Consecutive 16-microns-thick sections from single rat hearts containing the atrioventricular node were incubated with increasing concentrations of [125I]iodocyanopindolol. After exposure to [3H]Ultrofilm, optical densities corresponding to the atrioventricular node were determined by computerized densitometry after comparison with [125I]standards. The computer program LIGAND was used for analysis of receptor subtypes. Delineation of beta-adrenoceptor subtypes was achieved by incubating consecutive tissue sections with 50 pM [125I]iodocyanopindolol in the presence of increasing concentrations of the beta 1-selective antagonist atenolol or the beta 2-selective antagonist ICI 118,551. The atrioventricular node contains a higher concentration of beta-adrenoceptors than the adjacent interventricular septum. We estimated that the proportions of beta 1- and beta 2-adrenoceptors in the atrioventricular node were about 56% and 44% of the total binding capacity respectively.

Isolation and characterization of myosin heavy chain isozymes of the bovine conduction system.

To determine the characteristics of cardiac myosin in the conduction system, a pure Purkinje fiber preparation, consisting of atrioventricular nodes and the ventricular conduction system, was obtained from bovine hearts. Two types of myosin heavy chain isozymes, alpha-type and beta-type, were fractionated by affinity chromotography using monoclonal antibodies CMA19 and HMC50, which are specific for the alpha-type heavy chain and beta-type heavy chain, respectively. Competitive enzyme-linked immunosorbent assay demonstrated that the content of beta-type in the atrioventricular node (30-40%) was higher than that in atrial ordinary myocardium (10-20%) and that of the alpha-type was 30-40% in the ventricular conduction system, which was much higher than that in the ventricular ordinary myocardium (less than 10%). By one- and two-dimensional electrophoresis of the peptides produced by partial and complete digestion, the peptide compositions of alpha-type and beta-type in the conduction system were shown to be very similar to those of alpha-type and beta-type in ordinary myocardium, respectively. The CA2+-activated ATPase activity of myosin of the atrioventricular nodes was lower than that of ordinary atrial myosin (0.46 +/- 0.03 versus 0.58 +/- 0.02 mumol Pi/mg/min, mean +/- SEM, p less than 0.05) and in contrast, that of ventricular specialized myocardium was higher than that of myosin in the ventricular ordinary working myocardium (0.32 +/- 0.03 versus 0.22 +/- 0.01 mumol Pi/mg/min, p less than 0.05). This was in good agreement with the relative proportion of myosin isozymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Congenital polycystic tumor of the atrioventricular node (endodermal heterotopia, mesothelioma): a histogenetic appraisal with evidence for its endodermal origin.

The small, variously designated, primary atrioventricular node tumor has been considered to be of endothelial, endodermal, or mesothelial origin. To identify its derivation, we studied seven tumors using silver staining and immunocytochemical labeling with a variety of antibodies. Cytoplasmic argyrophil granules but not argentaffin granules were found in isolated cells among the more numerous tubule-lining cells in four tumors. Serotonin and calcitonin were demonstrable in seven and six tumors, respectively, in a similar distribution to that of the argyrophil cells. A positive reaction of different distribution from that of the argyrophil cells was noted in a varying number of tubule-lining cells for carcinoembryonic antigen, epithelial membrane antigen, and blood group antigen in seven, four, and seven tumors, respectively. No activity was noted in the tumor cells for factor VIII-related antigen or a number of peptides. An endodermal rather than mesothelial or epithelial origin for the tumor is substantiated by the presence of neuroendocrine cells in the midst of the more numerous carcinoembryonic-antigen-positive lining cells of the tumor tubules.

[Levels of DNA and sex chromatin bodies in the myocyte nuclei of different sections of the human heart]. / Soderzhanie DNK i telets polovogo khromatina v iadrakh miotsitov raznykh otdelov serdtsa cheloveka.

Nuclei of ventricular, atrial and atrioventricular node myocytes of normal and hypertrophied human heart were studied on squash preparations and on 12 micron sections after the Feulgen staining. The cytophotometric DNA measurements have shown a distinction in the degree of polyploidization of nuclei in different heart compartments. In contrast to ventricular and atrial myocardia, in which polyploid nuclei predominate, the conduction system myocytes contain 77-88% of diploid nuclei. A correlation between DNA content and the number of sex chromatin bodies was observed for myocyte nuclei from all the compartments under investigation.

Distribution of cardiac myosin isozymes in human conduction system. Immunohistochemical study using monoclonal antibodies.

To determine the presence and distribution of cardiac myosin isozymes in the human conduction system, we performed an immunohistochemical study using monoclonal antibodies CMA19 and HMC14, which are specific for myosin heavy chains of human atrial type (alpha-type) and ventricular type (beta-type), respectively. Serial frozen sections of human hearts were obtained from autopsy samples and examined by indirect immunofluorescence. Alpha-type was found in all myofibers of sinus node and atrio-ventricular node, and in 55.2 +/- 10.2% (mean +/- SD, n = 5) of the myofibers of ventricular conduction tissue, which consists of the bundle of His, bundle branches, and the Purkinje network. In contrast, beta-type was found in all myofibers of the atrio-ventricular node and ventricular conduction tissue, whereas almost all myofibers of the sinus node were unlabeled by HMC14. Although the number of ventricular myofibers labeled by CMA19 was small, the labeled myofibers were more numerous in the subepicardial region than in the subendocardial region. These findings show that the gene coding for alpha-type is expressed predominantly in specialized myocardium compared with the adjacent ordinary working myocardium.

Cytofluorometric nuclear DNA determinations on the atrioventricular nodal cells in human hearts.

In the human heart, it is well known that the polyploidization of working heart-muscle cells increases in proportion to increases in heart weight, but there has been no investigation of the process of polyploidization in the specialized heart-muscle cells of the cardiac conduction system which have a nerve-like function. In order to investigate the process of polyploidization in these cells, the nuclear DNA content of atrioventricular nodal cells was measured using cytofluorometry. Tissue samples taken from autopsied hearts without arrhythmias were embedded in paraffin blocks after Carnoy fixation. Blocks containing the atrioventricular conduction system were cut according to the serial sectioning method of Lev et al. The compact atrioventricular nodes were removed from thick paraffin sections (150 micron) under a stereomicroscope. The cells were then isolated by enzyme digestion and ultrasonic treatment. Smears of the isolated cells were double stained with azocarmin-G and acriflavine-Feulgen. Cytofluorometric DNA determinations of the DNA content of atrioventricular nodal cells were performed. Atrioventricular nodes were found to be composed of a large number of diploid cells and a small number of tetraploid cells. No octaploid cells were found. These findings reveal that the process of polyploidization in atrioventricular nodal cells is different from that found in working heart-muscle cells.

Somatostatin in the human heart and comparison with guinea pig and rat heart.

Somatostatin has been shown to have negative inotropic and chronotopic effects and to restore sinus rhythm in some cases of cardiac arrhythmia. Using acid extracts, regions of human heart were examined by radioimmunoassay to determine their somatostatin content. Mean (SD) concentrations of 4.1 (0.8) pmol/g and 2.9 (0.8) pmol/g were found in atrioventricular node and right atria respectively and were significantly higher than in other heart regions. Using fresh heart tissue from guinea pigs, somatostatin was localised to cardiac nerves by immunocytochemistry. Nerves containing somatostatin were most abundant in the atria, where the concentrations measured by radioimmunoassay were 7.6 (1.0) and 2.6 (0.4) pmol/g for right and left atria respectively. Somatostatin contained in cardiac nerves may have a physiological role in the cardiac conduction system.

The cardiac atrioventricular conduction system in familial amyloidosis with polyneuropathy. A clinico-pathologic study of six cases from Northern Sweden.

Cardiac conduction disturbances are frequent in amyloidosis with cardiac involvement, but the pathogenesis of these electrocardiographic abnormalities is not clear. In the present study, the conduction systems in six patients with the Swedish variety of familial amyloidosis with polyneuropathy (FAP), have been analyzed. The results suggest that in FAP, direct amyloid infiltration of the atrioventricular conduction system accounts for the majority of the electrocardiographic disturbances.

Cyclic adenosine 3', 5'-monophosphate, adenyl cyclase and phosphodiesterase in the conduction system of bovine heart.

Cyclic adenosine 3', 5'-monophosphate (cyclic AMP) and adenyl cyclase and phosphodiesterase activities were determined in the specialized myocardial tissue of the conduction system of bovine heart and then compared with those in the ordinary myocardial tissue. The conduction system was comprised of the atrioventricular node (A-V node), the His bundle and the right and the left bundle branches (RBB and LBB). The content of cyclic AMP was higher in the ordinary myocardial tissue than in the specialized myocardial tissue. In the specialized myocardial tissue, its content was highest in the A-V node and lower in the His bundle than in the LBB and the difference between the contents in the RBB and the LBB was not significant. Adenyl cyclase activity as well as the content of cyclic AMP was higher in the ordinary myocardial tissue than in the specialized myocardial tissue. Its activity was higher in the A-V node than in the His bundle or the RBB, and the activities in the His bundle, the RBB and the LBB were similar. Phosphodiesterase activity was higher in the ordinary myocardial tissue than in the A-V node, and the activities in these 4 sections of the conduction system were similar.