Arterial vascularization of the sinuatrial node in the embryonic rat heart.

We studied the embryological development of the extracoronary cardiac vessels, determining their origins, courses and terminations in embryonic rat hearts. The sinuatrial node is supplied by an extracoronary artery, which can originate from (a) the right internal mammary artery, as a nodal artery, based on its origin; (b) the internal mammary artery, or (c) the right subclavian artery as a collateral artery of the cardiac branch of the cardiomediastinal trunk. The intimate relations of the nodal artery with the sinus node make it possible to study, at the same time, the development of the sinuatrial node in the rat embryo. The sinuatrial node always develops before the nodal artery, which does not appear until 16 or 16.5 days of development.     

An immunocytochemical study of the sinuatrial node and atrioventricular conducting system of the rat for atrial natriuretic peptide distribution

Summary Immunocytochemical studies of the adult rat heart show that specific heart granules and atrial natriuretic peptide immunoreactivity are absent from the majority of the myocytes of the specialized nodes, atrioventricular bundle and bundle branches. Immunoreactive granules are present in a small proportion of the transitional sinuatrial and atrioventricular nodal myocytes but, in these regions, they are smaller than their counterparts in the general atrial myocytes. A rarer type of cell profile, identical to general atrial myocytes but lacking immunoreactive granules, is also present at the periphery of the sinuatrial node. A very small proportion of myocytes in the ventricular myocardium, generally in the subendocardial layers subjacent to the terminal ramifications of the bundle branches, contain a few immunoreactive granules.     

Cardiac conducting system of Gallus domesticus with special reference to the atrial bundles

Gross anatomy and histology of the cardiac conducting system of Gallus domesticus has been studied. Detailed histology of the atrium revealed for the first time, in the avian heart, the presence of three atrial bundles which communicate between the sinuatrial node and the atrioventricular node. Purkinje fibres in the subendocardium of the right atrium are observed. An atrioventricular segment comprising of the posterior end of the interatrial septum and the atrioventricular nodal region has been reported in which the three atrial bundles converge. The role of the atrial bundles in the cardiac contraction has been discussed.     

Probit analysis of the atrioventricular (AV) junctional tissues of the ferret heart

Probit frequency analysis, a graphic method for determining whether a population is normally distributed, skewed, or multinodal, was used to determine whether P cells are present in different regions of the AV junction in the ferret heart. This analysis indicated that at least 95% of the cells of the transitional zone, superficial AV node, deep AV node, and distal AV bundle of the ferret heart are morphologically homogeneous. In the proximal AV bundle a large cell population is found in addition to the AV bundle cells. The probit analysis was also used to characterize the shape of the cells of each region of the AV junction further. AV nodal cells are not as elongated as the atrial muscle cells and AV bundle cells. These nodal cells also do not branch as extensively as the AV bundle cells.     

Gut endoderm is involved in the transfer of left-right asymmetry from the node to the lateral plate mesoderm in the mouse embryo

In the mouse, the initial signals that establish left-right (LR) asymmetry are determined in the node by nodal flow. These signals are then transferred to the lateral plate mesoderm (LPM) through cellular and molecular mechanisms that are not well characterized. We hypothesized that endoderm might play a role in this process because it is tightly apposed to the node and covers the outer surface of the embryo, and, just after nodal flow is established, higher Ca(2+) flux has been reported on the left side near the node, most likely in the endoderm cells. Here we studied the role of endoderm cells in the transfer of the LR asymmetry signal by analyzing mouse Sox17 null mutant embryos, which possess endoderm-specific defects. Sox17(-/-) embryos showed no expression or significantly reduced expression of LR asymmetric genes in the left LPM. In Sox17 mutant endoderm, the localization of connexin proteins on the cell membrane was greatly reduced, resulting in defective gap junction formation, which appeared to be caused by incomplete development of organized epithelial structures. Our findings suggest an essential role of endoderm cells in the signal transfer step from the node to the LPM, possibly using gap junction communication to establish the LR axis of the mouse.     

Cardiac electrophysiologic effects of adaprolol maleate, a new beta-blocker, in closed chest dogs.

Adaprolol maleate (adaprolol) is a new beta-adrenergic receptor blocker. The cardiac electrophysiologic characteristics and the duration of action of adaprolol were studied in intact anesthetized dogs. The electrophysiologic parameters were evaluated before drug administration and 10 min after the administration of maintenance infusion of adaprolol (N = 5). The duration of action was measured during constant infusion of isoproterenol, giving the adaprolol as a single i.v. bolus in different concentrations (N = 5). Results of this study showed that adaprolol has marked electrophysiologic effects. Its major action was on sinus node; it prolonged the basic sinus cycle length and had significant effect on intrinsic automaticity as reflected by the prolonged corrected sinus node recovery time and sinuatrial conduction time. There was, also, direct effect on atrial function and AV nodal function. Adaprolol prolonged the effective refractory period of the His-Purkinje system and the ventricle. The onset of action was very rapid (within seconds) and the duration of action was relatively prolonged (3 hrs). The potency of adaprolol's electrophysiologic effects are higher compared to other widely used beta-blockers. Adaprolol appears to be a potent beta-blocker with particularly strong antiarrhythmic effect and it would be very useful in the treatment of both supraventricular and ventricular tachyarrhythmias and ectopic beats.     

Freeze-fracture studies of the sinoatrial and atrioventricular nodes of the caprine heart,with special reference to the nexus

Summary The caprine sinoatrial node (SAN) and atrioventricular node (AVN) were studied by freeze-fracture techniques, and their nexus or gap junction structure were compared with that of ordinary atrial and ventricular muscle cells. The general features of the nexus in both the SAN and AVN were essentially identical. Approximately two-thirds of the nexuses observed in the nodal cells consisted of typical macular arrangements of nexal particles, and the remaining third, of atypical configurations of either circular arrangements or linear arrays of particles in continuity with the macular nexuses. Such atypical nexuses were never observed in the ordinary adult myocardial cells. Quantitative analysis revealed that all of the nexuses in the nodal cells measured, were less than 0.1 m², whereas the majority of the nexuses in ordinary myocardial cells (64% in the atrium and 76% in the ventricle) were larger than 0.1 m². No significant differences in diameter and center-to-center distance of nexal particle were found between the nodal cells and ordinary myocardial cells.     

The ultrastructure of the sinuatrial ring bundle and of the caudal extension of the sinus node in the right atrium of the rabbit heart

Summary The cells of the sinuatrial ring bundle are smaller than the ordinary myocardial cells; they have a regular outline and a large content of myofibrils exhibiting distinct H-bands and M-lines. Rudimentary T-tubules are found. The cells are connected by frequent nexus junctions, desmosomes and regions of interfibrillar contact, both on the well developed intercalated discs and at the periphery of the cells.The cells in the cauda of the sinus node, which extends alongside the crista terminalis together with the right branch of the sinuatrial ring bundle, are irregularly outlined and have a highly variable diameter (1–10 m). They occur in clusters of closely packed cells. The content of myofibrils is sparse and the fibrils exhibit no M-lines and only weak H-bands. No T-tubules are found. The cells are not connected by intercalated discs and no nexus junctions are found.Both tissues contain unmyelinated nerves and nerve fibres. Varicosities with mitochondria and vesicles are found in close apposition to the muscle cells.     

The fine structure of the conducting system of the monkey heart (Macaca mulatta)

Summary In the sino-atrial (S-A) node of the monkey heart two types of muscle cells occur: 1. typical nodal cells which are the predominant cells and form the nodal fibers. 2. Intercalated clear cells with various diameters (4 to 12 m) and containing poorly developed myofibrils, rich in glycogen and demonstrating poor staining properties. These latter cells are dispersed, few in number, and never form discrete fibers of themselves, but are intercalated between the cell rows of the typical nodal fibers. Such intercalated clear cells become more numerous at the periphery of the node. Interconnection between the S-A node and the conventional atrial muscle is established by a progressive transformation of nodal fibers into atrial fibers producing an intermediate (or junctional) type of fiber at the nodal periphery. However, in addition, few nodal fibers make direct contact with the atrial cardiocytes. Our light and EM studies have failed to prove the existence of truly specialized internodal pathways. Nevertheless intercalated clear cells, nodal-like cells, junctional or intermediate type of cells are relatively frequent in valvular regions (Thebesian, Eustachian, A-V, fossa ovalis) and less frequent in other regions of the atrial wall.This study was conducted in part in the Department of Histology and Embryology of the Medical University in Budapest.     

Distribution and colocalization of neuropeptide Y- and tyrosine hydroxylase-like immunoreactivity in the guinea-pig heart

Summary The localization and distribution of neuropeptide Y-like immunoreactivity in the guinea-pig heart were studied by use of immunohistochemical methods. A widespread distribution of immunoreactive processes was observed in all regions of the heart. They occur either singly or together with several other immunoreactive processes and are most often aligned parallel to the myocardial bundles. A dense network of processes is present in the region of both the sinuatrial and atrioventricular nodes and single fibers are occasionally observed to be closely associated with nodal ganglion cells. Positive cell bodies were not seen within the heart. All small, medium and large coronary vessels are surrounded by a dense network of immunoreactive processes. A rich innervation at the media-adventitia junction of the aorta, pulmonary trunk, superior and inferior vena cava was also observed. Comparison of adjacent sections stained with antisera directed to avian pancreatic polypeptide, carboxyl-terminal hexapeptide of pancreatic polypeptide or neuropeptide Y demonstrated a very similar immunoreactive pattern, suggesting that these antisera are reacting with the same or a closely related substance. Likewise, the same immunoreactive patterns were observed in adjacent sections incubated in antiserum to neuropeptide Y or tyrosine hydroxylase, and analysis of elution-restained sections demonstrated that the same processes contain both neuropeptide Y- and tyrosine hydroxylase-like immunoreactivity. Neuropeptide Y- and tyrosine hydroxylase-like immunoreactivity was reduced by the same magnitude after treatment with the sympathetic neurotoxin 6-hydroxydopamine, but it was not affected by the primary sensory neurotoxin capsaicin. Furthermore, the pattern of neuropeptide Y- and tyrosine hydroxylase-like immunoreactivity did not match the staining patterns observed with antisera to vasoactive intestinal polypeptide or substance P or with the acetylcholinesterase staining pattern. In conclusion, neuropeptide Y-like immunoreactivity in the heart and great vessels coexists with that for catecholamines and is likely to originate from sympathetic ganglia.     

Distribution of vasoactive intestinal polypeptide-like immunoreactivity in the mammalian heart

Summary The distribution of vasoactive intestinal polypeptide (VIP) immunoreactivity has been studied in the mammalian heart and compared with that of neurotensin and substance P by use of light-microscopic peroxidase-antiperoxidase immunohistochemistry. VIP-immunoreactive cell bodies are present in intracardiac ganglia in various locations. VIP-immunoreactive nerve fibers predominate in the atria and the conduction system but are rare in the ventricles and occur in cardiac ganglia, endocardium, and epicardium. VIP-ergic nerves supply the coronary vasculature having a preference for the microvasculature and the nodal cells of the sinuatrial node. The large vessels of the heart and periarterial cardiac glomera also receive a VIP-immunoreactive nerve supply. There is partial co-distribution with neurotensin- and substance P-immunoreactive nerve fibers but no co-location in identical nerve fibers is detectable. The VIP-ergic cardiac innervation, which is probably predominantly intrinsic, may stem from postganglionic parasympathetic neurons and is less substantial than the more homogeneous neurotensin-ergic and substance P-ergic nervous supply which is probably extrinsic. The occurrence of an extrinsic VIP-ergic cardiac innervation cannot be excluded however. The differential histotopography of the multitarget cardiac nerves containing the cardiovascular active peptides VIP, neurotensin and substance P may suggest multiple and complex peptide-peptide and peptide-classical transmitter interactions. These may contribute to the regulation of various cardiac functions.     

Gap junctions in the rabbit sinoatrial node

In comparison to the cellular basis of pacemaking, the electrical interactions mediating synchronization and conduction in the sinoatrial node are poorly understood. Therefore, we have taken a combined immunohistochemical and electrophysiological approach to characterize gap junctions in the nodal area. We report that the pacemaker myocytes in the center of the rabbit sinoatrial node express the gap junction proteins connexin (Cx)40 and Cx46. In the periphery of the node, strands of pacemaker myocytes expressing Cx43 intermingle with strands expressing Cx40 and Cx46. Biophysical properties of gap junctions in isolated pairs of pacemaker myocytes were recorded under dual voltage clamp with the use of the perforated-patch method. Macroscopic junctional conductance ranged between 0.6 and 25 nS with a mean value of 7.5 nS. The junctional conductance did not show a pronounced sensitivity to the transjunctional potential difference. Single-channel recordings from pairs of pacemaker myocytes revealed populations of single-channel conductances at 133, 202, and 241 pS. With these single-channel conductances, the observed average macroscopic junctional conductance, 7.5 nS, would require only 30-60 open gap junction channels.     

猪冠状动脉的解剖学观察

本文对50例健康的商品猪心脏的铸型标本进行了观察,结果如下:左冠状动脉旋枝与锥旁室间枝的夹角为74.4±2.07度。对角枝出现率为24％,并证明了对角枝出现率与其夹角大小呈正比关系。窦房结枝84％来自右冠状动脉。房室结枝98％来自右冠状动脉。左房旋枝出现率为8％。室间隔的供血由锥旁室间枝的分枝负担61％,约为3/5,窦下室间枝的分技负担39％,约为2/5。室上嵴技、Kugel动脉、室间隔中枝和室间隔背倒前枝的出现率分别为78％、20％、68％和28％。心尖区的血液由左、右冠状动脉共同供应。50例左、右冠状动脉始部外径之比为1.2∶1。左、右冠状动脉在心膈面的分布类型以右强型为主。本文还讨论了猪冠状动脉与狗、人冠状动脉的异同。     

Ratio between Negative and Positive Lymph Nodes Is Suitable for Evaluation the Prognosis of Gastric Cancer Patients with Positive Node Metastasis

Objective

To date, there is no consensus to evaluate the most appropriate category of the nodal metastasis for precise predication the prognosis of gastric cancer patients with positive node metastasis after curative surgery.

Methods

We retrospectively analyzed the clinicopathologic characteristics and overall survival (OS) of 299 gastric cancer patients with positive node metastasis after curative surgery for evaluation the optimal category of the nodal metastasis.

Results

With the univariate and multivariate survival analyses, the depth of primary tumor invasion was identified as the independent predicators with the OS of 299 gastric cancer patients with nodal metastasis postoperatively, as were the number of positive lymph nodes (PLNs), the number of negative lymph nodes (NLNs), and the ratio between negative and positive lymph nodes (RNPL). The RNPL was identified to be more suitable for predication the OS of gastric cancer patients with positive node metastasis than the ratio between positive and dissected lymph nodes (RPDL) by using the stratum procedure of survival analysis. Besides, we found both PLNs and NLNs were independently correlated with OS of gastric cancer patients with nodal metastasis when RNPL, instead of RPDL, was controlled in the partial correlation model.

Conclusions

RNPL, a new category of the nodal metastasis, was suitable for predication the OS of gastric cancer patients with nodal metastasis after curative resection, as were the PLNs, and NLNs.     

Studies on mechano-perception in the Characeae: transduction of pressure signals into electrical signals

Mechano-perception by Chara cells was studied with an emphasis on the role of the nodal complex in transducing pressure signals into electrical signals. Three types of experimental material were used: (1) tandem internodal cells connected by a single layer of nodal cells; (2) single internodal cells, from which either apical or basal nodes were removed by ligation and cutting; (3) single internodes from which both nodes had been removed. Exposure to a hypertonic solution (sorbitol or sucrose) induced a depolarization at the node in 1 and 2. Depolarization did not occur at the ligated end of the cell in 2, or at all in 3. Addition of K+ increased the magnitude of the response, whilst it was significantly decreased by the divalent cations, Ca2+ and Mg2+. Electrical resistance decreased at the node during the depolarization, showing that a passive diffusion potential was responsible. I suggest that the change in the trans-nodal hydraulic pressure difference mechanically stretches the plasma membrane, and this induces the electrical depolarization.     

In-vivo dosimetry comparison of supraclavicular junction dose for breast and chest-wall patients with and without deep inspiration breath hold (DIBH)

PurposeThe use of deep inspiration breath-hold (DIBH) for patients with left-sided breast cancer reduces cardiac dose, with the aim of reducing the risk of major coronary events. However, this technique has not been universally adopted for patients requiring regional nodal irradiation (RNI) with one concern related to the junction dose. This study evaluates the dose received at the junction for both DIBH and free-breathing patients having tangential breast/chest wall radiation and regional nodal radiation treated with 3D-conformal or hybrid IMRT radiotherapy.MethodsIn-vivo dosimetry measurements utilizing EBT3 GafChromic™ film were performed for 19 patients during three fractions over their course of treatment. The mean junction dose and variability in junction dose were compared between the DIBH and free breathing patients.ResultsOur results show that for voluntary DIBH (v-DIBH) patients the junction dose is more variable between fractions. However, when comparing the average junction dose for DIBH and free breathing patients over the three measurements, the difference was small and not statistically significant. A larger difference was seen when patient measurements were analysed based on treatment linac.ConclusionsThese results show that the mean junction dose is not significantly compromised by the use of v-DIBH. The small possibility of a change in junction dose due to breathing technique should be weighed against the proven increased risks associated with excess cardiac dose received by free-breathing patients. If junction dose is of concern, an in-vivo study, such as this one, could allow cautious introduction of DIBH for patients requiring supraclavicular irradiation.     

On the impulse conducting system of the monkey heart (Macaca mulatta)

Summary The atrio-ventricular (A-V) node of the monkey heart is located in the focus of converging atrial muscle. Three main atrial muscle strands, coming from the atrio-ventricular ring, the dorsal wall of the atria, and the ventral part of the atrial septum, converge in the nodal region where they overlap and are interconnected. The junctional type of fibers establishing interconnection between the atrial muscle and the nodal tissue are not strictly localized at the periphery of the node, but may be traced further, along the A-V ring and coronary sinus. The A-V node consists of a loose peripheral and a compact distal part. In the former, typical nodal fibers were found, while the compact part shows an important individual variation in structure and cell-types. In some monkey hearts, the nodal fibers gradually become broader bundle fibers, while in other specimens the junctional fibers surround the compact part and than penetrate the nodal-His (N-H) region. These junctional fibers become nodal fibers or are in terminal contact with large clear cells up to 50 in diameter. Clear cells of various diameters are often intercalated between the cell rows of the nodal and His-bundle fibers and may form a distinct cellular gate between the node and the His-bundle.This study was conducted in part in the Department of Histology and Embryology of the Medical University in Budapest.     

Paranodal Schwann cell mitochondria in spinal roots of the cat. An ultrastructural morphometric analysis

We have calculated the number of paranodal Schwann cell mitochondria in adult feline ventral and dorsal lumbar spinal roots using ultrastructural serial section analysis. Distinct accumulations of paranodal mitochondria were noted in nerve fibres more than 4-5 mm in diameter. The calculated number of paranodal mitochondria increased linearly with fibre diameter from a few hundred up to 20 000-30 000 per node. A linear increase in the number of paranodal mitochondria per node also appeared as a function of nodal variables such as ‘nodal axon membrane area’, ‘nodal Schwann cell membrane area’, and ‘node gap extracellular volume’. In large fibres (D=15-18 mm), a calculated number of about 20 000 paranodal Schwann cell mitochondria were accumulated at each node of Ranvier and related to nodal axon membrane area of about 20 mm2. Our calculations indicate that, on the average, 1000 paranodal Schwann cell mitochondria with a total volume of 6.7 mm3, a total outer membrane area of 250 mm2 and a total inner membrane area of 580 mm2 projected to each mm2 of the nodal axon membrane via the nodal Schwann cell brush border.     

Ion-exchange at the node of Ranvier

Synopisis A study has been made of the cation-binding capacity of nodal regions of rat peripheral nerve fibres. Material within the nodal gap was found to bind ferric (Fe³⁺), barium (Ba²⁺) and potassium (K⁺) ions, the affinity for cations decreasing with ionic valency. The nature of the bond to presumed fixed anionic sites at the node was deduced to be electrostatic, the strength of the bond depending on the charge of the cation and also probably on its hydrated ionic diameter. Cation-exchange was demonstrated at the node histochemically. Material with ion-exchange properties is presumed to overlay the free surface of the electrically excitable axon membrane at the nodal gap. The effects of a variety of enzymes and organic solvents on cation uptake at the node were determined and suggestions are made as to the chemical nature of the anionic binding sites. The physiological implications of these findings are discussed within the framework of present concepts concerning the conduction of the nervous impulse.     

Clinicopathologic Predictors of Survival in Patients with Desmoplastic Melanoma

Background and Objectives

Desmoplastic melanoma is a unique subtype of melanoma which typically affects older patients who often have comorbidities that can adversely affect survival. We sought to identify melanoma-specific factors influencing survival in patients with desmoplastic melanoma.

Methods

Retrospective review from 1993 to 2011 identified 316 patients with primary desmoplastic melanoma. Clinicopathologic characteristics were correlated with nodal status and outcome.

Results

Fifty-five patients (17.4%) had nodal disease: 33 had a positive sentinel lymph node biopsy and 22 developed nodal recurrences (no sentinel lymph node biopsy or false-negative sentinel lymph node biopsy). Nodal disease occurred more often in younger patients and in cases with mixed compared with pure histology (26.7% vs. 14.6%); both of these variables significantly predicted nodal status on multivariable analysis (p<0.05). After a median follow-up of 5.3 years, recurrence developed in 87 patients (27.5%), and 111 deaths occurred. The cause of death was known in 79 cases, with 47 deaths (59.5%) being melanoma-related. On multivariable analysis, Breslow thickness, mitotic rate ≥1/mm² and nodal status significantly predicted melanoma-specific survival (p<0.05).

Conclusions

Nodal status predicts melanoma-specific survival in patients with desmoplastic melanoma. However, since patients with desmoplastic melanoma represent an older population, and a considerable proportion of deaths are not melanoma-related (40.5%), comorbidities should be carefully considered in making staging and treatment decisions in this population.