Sinoatrial node pacemaker cells share dominant biological properties with glutamatergic neurons

Activation of the heart normally begins in the sinoatrial node (SAN). Electrical impulses spontaneously released by SAN pacemaker cells (SANPCs) trigger the contraction of the heart. However, the cellular nature of SANPCs remains controversial. Here, we report that SANPCs exhibit glutamatergic neuron-like properties. By comparing the single-cell transcriptome of SANPCs with that of cells from primary visual cortex in mouse, we found that SANPCs co-clustered with cortical neurons. Tissue and cellular imaging confirmed that SANPCs contained key elements of glutamatergic neurotransmitter system, expressing genes encoding glutamate synthesis pathway (Gls), ionotropic and metabotropic glutamate receptors (Grina, Gria3, Grm1 and Grm5), and glutamate transporters (Slc17a7). SANPCs highly expressed cell markers of glutamatergic neurons (Snap25 and Slc17a7), whereas Gad1, a marker of GABAergic neurons, was negative. Functional studies revealed that inhibition of glutamate receptors or transporters reduced spontaneous pacing frequency of isolated SAN tissues and spontaneous Ca

Role of over-expression of TBX3 and TBX18 in the enrichment and differentiation of human induced pluripotent stem cells into sinoatrial node-like cells / 中国修复重建外科杂志

Objective : To explore the role of over-expression of TBX3 and TBX18 in inducing human induced pluripotent stem cells (HiPS) to enrich and differentiate into sinoatrial node-like cells. Methods: The expression of stemness markers OCT3/4, SOX2, and NANOG in HiPS was detected by real-time fluorescence quantitative PCR (qRT- PCR), and compared with human embryonic stem cells (hESCs). Immunofluorescence staining was used to observe the expression of HiPS stemness markers OCT3/4, NANOG, SSEA4, and TRA-1-60. The HiPS were directional differentiated into cardiomyocytes, the expressions of ISL1, NK2 homeobox 5 (NKX2-5), ACTN1, and TNNT2 were detected by qRT-PCR, and human adult cardiomyocytes (hACM) were used as positive control. Immunofluorescence staining was used to observe the expressions of NKX2-5, cardiac troponin (cTnT), α-actinin, atria myosin light chain 2A (MLC-2A), and ventricular myosin light chain 2V (MLC-2V). The positive rate of α-actinin was detected by flow cytometry. On the 3rd day after HiPS were differentiated into cardiomyocytes (mesodermal stage), lentiviral over-expressions of sinoatrial node-related genes TBX3 and TBX18 were carried out for 21 days. The relative expressions of specific markers TBX3, TBX18, SHOX2, NKX2-5, HCN4, and HCN1 in sinoatrial node cells were detected by qRT-PCR, and compared with enhanced green fluorescent protein blank virus. Results : OCT3/4, SOX2, and NANOG were highly expressed in HiPS and ESCs, and there was no significant difference in the relative expression of each gene ( P>0.05); OCT3/4 and NANOG were specifically distributed in the nucleus of HiPS, while SSEA4 and TRA-1-60 were distributed in the cell membrane. The relative expressions of ISL1 gene at 5, 7, 21, and 28 days and NKX2-5 gene at 7, 21, and 28 days of HiPS differentiation into cardiomyocytes were significantly higher than those of hACM ( P0.05). There was no significant difference in the relative expression of each gene between the over-expressed TBX18 group and the control group ( P>0.05). Conclusion: HiPS and hESCs have similar pluripotency, and we have established a stable method for maintaining and culturing the stemness of HiPS. A technological platform for the efficient differentiation of HiPS into cardiomyocytes has been successfully established. Although TBX3 and TBX18 do not play a significant role in promoting the enrichment and differentiation of HiPS into sinoatrial node-like cells, TBX3 shows a certain promoting trend, which can be further explored in the future.

Variação nos tipos de irrigação do nodo sinoatrial em cães de diferentes raças / Variation in irrigation of the sinoatrial node in dogs of different breeds

Considerando a heterogeneidade anatômica e eletrofisiológica do nodo sinoatrial para a geração e propagação do potencial de ação, bem como as particularidades relacionadas a origem da sua irrigação sanguínea, este trabalho teve como objetivo analisar o comportamento das artérias envolvidas na irrigação do nodo sinoatrial em cães realizando uma análise descritiva e comparativa entre diferentes raças estudadas, detalhando a origem, o percurso e a ramescência dos vasos, assim como a eventual ocorrência de anastomoses. Ao todo analisamos resultados obtidos em 240 corações, os quais foram fixados em solução de formalina 10% e submetidos a diafanização de Spalteholz. A irrigação deste ocorre mediante colaterais oriundos do ramo circunflexo direito ou ramo circunflexo esquerdo, mostrando particularidades diferentes para cada raça. Assim, predominantemente, nas raças ora estudadas a irrigação arterial do nodo sinoatrial depende exclusivamente (63,6%), ou de anastomoses de colaterais da artéria coronária direita, havendo também participação dos ramo proximal atrial direito e intermédio atrial direito. Menos frequentemente (15,4%) o suprimento sanguíneo ocorre exclusivamente por conta do ramo proximal atrial esquerdo, oriundo do ramo circunflexo da artéria coronária esquerda. Os dados aqui apresentados sobre a origem da irrigação sanguínea do nodo sinoatrial e a ramescência dos vasos envolvidos nesta tarefa representam conhecimento fundamental para o desenvolvimento da clínica-cirúrgica em cães, da patologia e trabalhos de natureza experimental.(AU)

Considering the anatomical and electrophysiological heterogeneity of the sinoatrial node for generation and propagation of the action potential, as well as the particularities relating to the origin of blood nutrition, this study aimed to analyze the behavior of arteries involved in irrigation of the sinoatrial node in dogs performing a descriptive and comparative analysis between different breeds, with emphasis in the origin, pathway and branching of vessels, as well as the presence of anastomoses. Totally, 240 hearts were fixed in solution of formalin 10% and subjected to Spalteholz diaphanization. The vascularization of the sinoatrial node occurs by the right circumflex branch or left circumflex branch, showing several particularities according to the breed. Thus, predominantly in the studied breeds, the blood supply of the sinoatrial node depends exclusively (63.6%) or from anastomosis of the right coronary artery. There is also participation of right atrial proximal branch and right atrial intermediary branch. Less often (15.4%) the blood supply occurs exclusively from the left atrial proximal branch, which is a branch of the circumflex branch of the left coronary artery. In summary, our results related to the origin of the sinoatrial node blood nutrition and the branching of vessels involved on that represents a fundamental knowledge for the development and improvement of surgery in dogs, as well as for pathology and experimental research.(AU)

Compound Heterozygous SCN5A Mutations in a Toddler - Are they Associated with a More Severe Phenotype? / Heterozigose Composta no Gene SCN5A em Criança - Há Associação com Gravidade da Doença?

Abstract Compound heterozygosity has been described in inherited arrhythmias, and usually associated with a more severe phenotype. Reports of this occurrence in Brugada syndrome patients are still rare. We report a study of genotype-phenotype correlation after the identification of new variants by genetic testing. We describe the case of an affected child with a combination of two different likely pathogenic SCN5A variants, presenting sinus node dysfunction, flutter and atrial fibrillation, prolonged HV interval, spontaneous type 1 Brugada pattern in the prepubescent age and familiar history of sudden death.

Resumo A heterozigose composta é descrita em arritmias hereditárias, geralmente associada a um fenótipo mais grave. Relatos dessa ocorrência em pacientes com síndrome de Brugada ainda são raros. Neste estudo, descrevemos o caso de uma criança com a combinação de duas novas variantes distintas no gene SCN5A, apresentando disfunção do nó sinusal, flutter e fibrilação atrial, intervalo HV prolongado, padrão tipo 1 espontâneo de Brugada na idade pré-puberal e história familiar de morte súbita.

Establishment of a method to isolate sinoatrial node cells of adult rats and observation of the expression of sodium subtypes / 西安交通大学学报(医学版)

Objective To establish a method to isolate single sinoatrial node cells of adult rats and observe the cells'morphological structure and the expression of sodium channel subtype so as to provide experimental basis for further research on the role of sodium channel in sinoatrial node function.Methods We isolated adult rat sinoatrial node tissue and cut it into slices about 2 mm in width,digested the slices with type Ⅱ collagenase combinate protease, and observed the cells' morphological structure. We then performed immunofluorescence staining with HCN4 and laser confocal imaging to identify cells and observe the expressions of Nav1 .1 ,Nav1 .2 , Nav1.3,Nav1.5,Nav1.6,Nav1.7,Nav1.8 and Nav1.9.Results The isolated cells had spindle-like,arc-like, and slender and curved shapes,but were mainly spindle-shaped.The stripes of the cells were clear,had good bioactivity and could survive 6-8 hours.Sodium channels Nav1.1,Nav1.5,Nav1.6,Nav1.7,Nav1.8,and Nav1.9 were positively expressed in adult rat sinoatrial node cells,while Nav1 .2 and Nav1 .3 were negatively expressed. Conclusion The method of digesting and isolating adult rat sinoatrial node cells with type Ⅱ collagenase combinate protease is reliable,and sodium channel subtypes are differently expressed in sinoatrial node cells.

Establishment of a method to isolate sinoatrial node cells of adult rats and observation of the expression of sodium subtypes / 西安交通大学学报(医学版)

Objective To establish a method to isolate single sinoatrial node cells of adult rats and observe the cells'morphological structure and the expression of sodium channel subtype so as to provide experimental basis for further research on the role of sodium channel in sinoatrial node function.Methods We isolated adult rat sinoatrial node tissue and cut it into slices about 2 mm in width,digested the slices with type Ⅱ collagenase combinate protease, and observed the cells' morphological structure. We then performed immunofluorescence staining with HCN4 and laser confocal imaging to identify cells and observe the expressions of Nav1 .1 ,Nav1 .2 , Nav1.3,Nav1.5,Nav1.6,Nav1.7,Nav1.8 and Nav1.9.Results The isolated cells had spindle-like,arc-like, and slender and curved shapes,but were mainly spindle-shaped.The stripes of the cells were clear,had good bioactivity and could survive 6-8 hours.Sodium channels Nav1.1,Nav1.5,Nav1.6,Nav1.7,Nav1.8,and Nav1.9 were positively expressed in adult rat sinoatrial node cells,while Nav1 .2 and Nav1 .3 were negatively expressed. Conclusion The method of digesting and isolating adult rat sinoatrial node cells with type Ⅱ collagenase combinate protease is reliable,and sodium channel subtypes are differently expressed in sinoatrial node cells.

The efficiency of Ivabradine therapy in heart failure in elderly patients / 中华老年医学杂志

Objectives To evaluate the efficacy and safety of administering Ivabradine in the elder patients with chronic heart failure(HF).Methods Totally 52 outpatients with chronic stable HF in Fuwai Hospital and Anzhen Hospital from August 2015 to February 2016,with heart rates (HR)of ＞70 bpmafter optimized medical therapy were selected and administrated Ivabradine for 3 months(Ivabradine group).50 patients who received optimized medical therapy except Ivabradine for economic or other reasons were recruited as control group during the same period.Initial dose of Ivabradine was 2.5 mg two times a day,up to a maximum of 7.5 mg two times a day,adjusting the dose according to HR.Resting HR of the patients was maintained around 60 beats/min and not lower than 55 beats/min.HR,N-terminal pro-brain natriuretic peptide (NT-proBNP),6-minute walk distance,Minnesota heart failure quality of life(MLHFQ),left ventricular ejection fraction(LVEF) and adverse effects were recorded.Results At baseline,no significant differences were found in HR,NT-proBNP,the scores of MLHFQ,6-minute walk distance (all P＞ 0.05) between Ivabradine group and control group.After 3 months of treatment,compared with control group,Ivabradine group showed significantly decreased levels of HR,the scores of MLHFQ and NT-proBNP(allP＜0.01),and significantly increased 6-minute walk distance and LVEF(all P＜0.01).Compared with baseline data,Ivabradine treatment showed the decreased levels of HR [(69.5 ± 10.2)bpm vs.(80.2 ± 7.8)bpm,P＜0.05],the scores of MLHFQ [(14.9±4.3)scores vs.(23.5±6.2)scores(P＜0.05)]and NT-proBNP [1 682 ng/L (212-3 628) vs.2 450 (254-5 344) ng/L,P ＜ 0.05] significantly,and showed the significantly increased levels of 6-minute walk distance [(386.4 ± 101.8)m vs.(282.9 ± 86.3)m,P＜ 0.05]and LVEF [(40.0±6.0)％vs.(31.0±7.0)％ (P＜0.05)].Few adverse effects were recorded.Conclusions In elderly outpatients with stable HF,Ivabradine treatment is effective and safe.

«Las otras¼ bradicardias / Those "other" bradycardias

La bradicardia es un hallazgo frecuente en el contexto de pacientes hospitalizados. Algunas veces se detecta de manera incidental y se minimizan sus implicaciones clínicas. No obstante, en ocasiones se asocia con la presencia de síntomas o compromiso hemodinámico en los pacientes que ameritan una intervención adicional. La etiología de la bradicardia no siempre es fácil de determinar y no es extraño que se inicien múltiples estudios con el fin de aclarar el porqué de la situación. Los clínicos estamos familiarizados con el efecto farmacológico y los efectos adversos de variados medicamentos que usamos cotidianamente. A pesar de esto, existen múltiples medicamentos con potencial para desarrollar la bradicardia como respuesta a una propiedad farmacológica menos conocida o en relación con efectos adversos infrecuentes, pero sin duda significativos. El objetivo de la presente revisión es repasar las propiedades farmacológicas y el impacto clínico de algunas sustancias que se han relacionado con la bradicardia, más allá de los que todos conocemos, con el fin de orientar las intervenciones a realizar en los pacientes con causas farmacológicas y reversibles de la bradicardia.

Bradycardia is a common finding in the context of hospitalized patients. Sometimes it is incidentally detected and its clinical implications are minimized. But sometimes it is associated with the presence of symptoms or hemodynamic compromise in patients who warrant further intervention. The etiology of the bradycardia is not always easy to determine and it is not surprising that many studies are initiated in order to clarify the reason for the situation. Clinicians are familiar with the pharmacological and adverse effects of various drugs we use every day. Despite this, there are many drugs with potential to develop bradycardia in response to a less known pharmacological properties or effects related to rare but certainly significant effects. The aim of this review is to explain the pharmacological properties and clinical impact of some substances that have been associated with bradycardia, beyond which we all know, in order to target interventions to be performed in patients with pharmacological and reversible causes of bradycardia.

Effect of dexmedetomidine on rabbit heart rate: in vitro and in vivo experiments / 中华麻醉学杂志

Objective To evaluate the effect of dexmedetomidine on heart rate (HR) of rabbits through in vitro and in vivo experiments, and investigate the mechanism by which dexmedetomidine lowered HR.Methods In vitro experiment Healthy adult rabbits of both sexes, weighing 2.0-2.5 kg, aged 8-10 weeks, were studied.The 24 isolated hearts passively perfused in a Langendorff apparatus were randomly divided into 3 groups (n =8 each) using a random number table: control group (group C) , and dexmedetomidine 3 and 30 ng/ml groups (D1 and D2 groups).The isolated hearts were continuously perfused with K-H solution for 45 min in group C.After 15 min of equilibration, the isolated hearts were perfused for 30 min with K-H solution containing dexmedetomidine 3 and 30 ng/ml in D1 and D2 groups, respectively.At 15 min of equilibration, and at 15 and 30 min of perfusion with K-H solution containing dexmedetomidine, HR and left ventricular systolic pressure (LVSP) were recorded.In vivo experiment Twenty-five healthy adult rabbits of both sexes, weighing 2.0-2.5 kg, aged 8-10 weeks, were randomly divided into 5 groups (n=5 each) using a random number table: dexmedetomidine 3, 6, 9, 12, and 15 μg/kg groups (D3, D6, D9, D12, D15groups), to receive the corresponding doses of dexmedetomidine which was intravenously infused over 10 min.HR and mean arterial pressure were monitored and recorded before administration (T0) , and at 15 and 40 min after administration (T1,2).The correlation between doses of dexmedetomidine and change rate of HR was tested by Spearman correlation analysis.Results In vitro experiment Compared with group C, no significant changes were found in HR and LVSP at each time point in D1 and D2 groups (P＞0.05).In vivo experiment Compared with those at T0 , HR at T1 in D6 and D9 groups, HR at T1,2 in D12 and D15 groups, and mean arterial pressure at T1,2in D6, D9, and D12 groups were significantly decreased (P＜0.05) , and no significant change was found in HR at each time point in group D3 (P＞0.05).The correlation coefficient between doses of dexmedetomidine and change rate of HR was 0.944 (P＜0.05).Conclusion The mechanism by which dexmedetomidine lowers HR of rabbits is not related to direct inhibition of sinoatrial nodes, but associated with the balance of autonomic nervous system.

The clinical analysis of 212 cases of transesophageal atrial pacing (TEAP) / 中国基层医药

Objective To discuss the clinical application value of transesophageal atrial pacing ( TEAP) in basic general hospitals.Methods A total of 212 subjects were selected,with dizziness,syncope,paroxysmal palpita-tions and other clinical symptoms and electrocardiogram showed sinus slow, atrioventricular block, short PR interval period,or with the first urgent symptom of tachycardia.The author doubted these symptoms were due to decreased function of the sinoatrial and atrioventricular node or Paroxysmal Supraventricular Tachycardia (PSVT),and treated them with TEAP with xd-5a.Results 121 cases (57.1%) were positive,83 cases(68.6%) of sinoatrial node dys-function,38 cases(31.4%) of PSVT,then sinoatrial node dysfunction were given atropine load experiment and double checked TEAP.The authors detected 57 cases of non-increased vagus nerve tension in 83 positive cases,29 cases (20.1%) of sinoatrial node hypofunction,8 cases of atrioventricular node hypofunction,14 cases of double node hypofunction,6 cases of tachycardia-bradycardia syndrome;38 cases(31.4%) of PSVT,20 cases of dual atrioven-tricular nodal pathways(DAVNP),12 cases of atrioventricular bypass,4 cases of atrial tachycardia(AT),2 cases of ventricular tachycardia( VT);12 cases from 38 cases of positive results manifested as the first urgent symptom of achy-cardia,included 5 cases of DAVNP,5 cases of atrioventricular bypass,overdrive pacing terminated tachycardia suc-cessfully,2 cases of male VT,1 case terminated tachycardia through giving intravenous amiodarone successfully,1 case was taken electrical cardioversion uccessfully.Conclusion The common causes of slow sinus and atrioventricular block and the common cardiac electrophysiological types of PSVT and VT were detected through TEAP examination with the best diagnostic and differential diagnostic value.According to diagnosis guide,clinicians adopted correct and effective treatment strategies with good clinical application value.The author suggest this methods should be used in clinical,especially in basic general hospitals.

Changes of HCN4, Cx43 Expression in the Sinoatrial Node of Electric Shock Death / 法医学杂志

Objective T o investigate the expression of hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (H C N 4) and connexin43 (C x43) in the sinoatrial node of electric shock death. Meth-ods As experim ental group, 34 cases of electric shock death who had definite current m ark evidence were selected from pathology departm ent of X uzhou M edical C ollege from 2010 to 2013. As the control group, 20 cases of fatal severe craniocerebral injury in traffic accidents were chosen. T he expressions of H C N 4 and C x43 in the sinoatrial node were observed by im m unohistochem ical technology. Results H C N 4 positive cells expressed in the cell m em brane and cytoplasm of the sinoatrial node. C x43 positive cells expressed in the cell m em brane and cytoplasm of T cells and m yocardial cells. T he expression of H C N 4 was significantly higher than that of the control group (P<0.05) and the expression of C x43 was signifi-cantly lower than that of the control group (P<0.05). Conclusion T he changes of H C N 4 and C x43 ex-pressions in the sinoatrial node illustrate electric shock death m ight be related to the abnorm alities of cardiac electrophysiology and conduction.

Effect of ferulic acid on the apoptosis andβ-tubulin of rabbit sinoatrial node cell in vitro injured by low glucose and hypoxic / 国际中医中药杂志

Objective To observe the effects of ferulic acid on cell apoptosis andβ-tubulinin vitro of rabbit sinoatrial node injured by hypoxia and low glucose, and to explore its mechanism.Methods Model cells were established on sinoatrial node cells from newborn rabbit by performing deprivation of oxygen and glucose. Then the model cells were divided into 5 groups: a normal control group, a model group, ferulic acid high, medium and low dose group. The normal control group and the model group were treated with equal volume of culture medium, and the three volume ferulic acid groups were treated with ferulic acid of 100, 20, and 10μg/ml respectively. Flow cytometry, laser scanning confocal microscopy were used to observe the sinoatrial node apoptosis rate and cytoskeleton proteinβ-tubulin in each group.Results Apoptosis rate of the model group was obviously higher than the normal group (56.95% ± 11.99%vs. 31.45% ± 6.32%,P<0.01), whileβ-tubulin cleavage was significantly lower than the normal group (5.141 ± 0.218vs. 8.035 ± 0.762,P<0.01). Apoptosis rate of ferulic acid high, medium dose group were significantly lower than the model group (24.85% ± 6.34%, 26.70% ± 9.84%vs. 56.95% ± 11.99%,P<0.01),β-tubulin structure were significantly more complete compared with the model group (7.927 ± 0.357, 5.961 ± 0.351vs. 5.141 ± 0.218,P<0.01).Conclusions Ferulic acid can suppress apoptosis of sinoatrial node cells caused by low glucose and oxygen. Protecting the sinoatrial node cell skeleton protein ofβ-tubulin may be one of the mechanisms.

Clinical application value of transesophageal atrial pacing combined with atropine load experiment in the diagnosis of the lesions of sinoatrial node and atrioventricular node / 中国综合临床

Objective To evaluate the clinical application value of transesophageal atrial pacing (TEAP) combined with atropine load experiment in the diagnosis of the lesions of sinoatrial node and atrioventricular node.Methods One hundred and forty-four cases selected from the outpatient and hospitalized patients in the People's Hospital of Changji Hui Autonomous Prefecture from September 2009 to December 2012,who with dizziness, syncope and other clinical symptoms and electrocardiogram showe.TEAP combined with atropine load experiment were given to these patients.Results (1) The authors detected in all patients,83 cases (57.6％) were positive, among which, 48 cases (57.8％) male, 35 cases (42.2％) female.(2) The authors detected 57 cases(39.6％) non-increased vagus nerve tension cases in 83 positive cases,among which 33 cases (57.9％) male, 24 cases (42.1％) female;Among which 29 cases (20.1％) were sinoatrial node hypofunction, and 16 cases(55.2％) male;8 cases(5.6％) were atrioventricular node hypofunction,and 4 cases(50％) male;14 cases(9.7％) were double node hypofunction, and 10 cases (71.4％) male;6 cases (4.2％) were tachycardia-bradycardia syndrome, and 3 cases (50％) male;among which, a long interval of greater than 3 seconds appeared when we stimulate one 84 years old man with S1S1 stimulate way, immediately pressed protective pacemaker until his own sinus rhythm was restored, as a safety precaution, stoped further examination and classified him as sick sinus group.Conclusion Detect the common causes of slow sinus and atrioventricular block,such as the sinoatrial node dysfunction, atrioventricular node dysfunction, double node dysfunction and increased vagus nerve tension through TEAP combined with atropine load experiment.Consider that this methods have the best diagnostic value in decreasing its rate of false positivity,and should be used as a necessary check before implantation of pacemaker in such patients, suitable used in clinical, especially in basic general hospitals.

Function and Dysfunction of Human Sinoatrial Node

Sinoatrial node (SAN) automaticity is jointly regulated by a voltage (cyclic activation and deactivation of membrane ion channels) and Ca2+ clocks (rhythmic spontaneous sarcoplasmic reticulum Ca2+ release). Using optical mapping in Langendorff-perfused canine right atrium, we previously demonstrated that the beta-adrenergic stimulation pushes the leading pacemaker to the superior SAN, which has the fastest activation rate and the most robust late diastolic intracellular calcium (Cai) elevation. Dysfunction of the superior SAN is commonly observed in animal models of heart failure and atrial fibrillation (AF), which are known to be associated with abnormal SAN automaticity. Using the 3D electroanatomic mapping techniques, we demonstrated that superior SAN served as the earliest atrial activation site (EAS) during sympathetic stimulation in healthy humans. In contrast, unresponsiveness of superior SAN to sympathetic stimulation was a characteristic finding in patients with AF and SAN dysfunction, and the 3D electroanatomic mapping technique had better diagnostic sensitivity than corrected SAN recovery time testing. However, both tests have significant limitations in detecting patients with symptomatic sick sinus syndrome. Recently, we reported that the location of the EAS can be predicted by the amplitudes of P-wave in the inferior leads. The inferior P-wave amplitudes can also be used to assess the superior SAN responsiveness to sympathetic stimulation. Inverted or isoelectric P-waves at baseline that fail to normalize during isoproterenol infusion suggest SAN dysfunction. P-wave morphology analyses may be helpful in determining the SAN function in patients at risk of symptomatic sick sinus syndrome.

Bradicardia y convulsiones: una relación multicausal / Bradycardia and seizures: a multi-causal relationship

La disfunción del nodo sinusal consiste en una alteración en la generación del impulso en el nodo sinusal. Su principal causa es la degeneración fibrosa del tejido sinusal. Los casos asociados a convulsiones son multicausales y se deben a los efectos cardiodepresores de los anticonvulsivantes o de sus diluyentes; así mismo se pueden presentar casos de bradicardia y asistolia inducidos por las descargas epilépticas. Se expone el caso de una paciente con status epiléptico tratada con fenitoína endovenosa, quien recibía previamente carbamazepina y desarrolló disfunción del nodo sinusal considerada como un efecto secundario tóxico de su medicación anticonvulsivante.

Sinus node dysfunction is an alteration in the impulse generation in the sinus node. Its main cause is the fibrous degeneration of the sinus tissue. Cases associated with seizures have multiple causes and are due to the cardio-depressant effects of anticonvulsants or its diluents. Likewise, there may be cases of bradycardia and asystole induced by epileptic discharges. Here is presented the case of a female patient with status epilepticus who was treated with intravenous phenytoin and was previously receiving and developed sinus node dysfunction which was considered as a toxic side effect of her anticonvulsant medication.

Effect of Tongyang Huoxue Recipe on Cytoskeleton Protein β-tubulin of Ischemia Reperfusion Injured Sinoatrial Node Cell in Rabbits / 中国中医药信息杂志

Objective To observe the effects of Tongyang Huoxue Recipe on cytoskeleton proteinβ-tubulin of ischemia reperfusion injured sinoatrial node cell in rabbits;To discuss its mechanisms in the treatment of sick sinus syndrome. Methods Sinoatrial node cells were obtained from newborn rabbit. Oxygen and glucose were deprived to simulate ischemia and were restored to simulate reperfusion. Cells were divided into 5 groups. Tongyang Huoxue Recipe high-, medium-, low dose groups were given corresponding medicine (final concentrations of 100, 20, 10 μg/mL). The normal group and model group were given equal volume of culture medium. Enzyme mark instrument and laser scanning confocal microscopy were used to observe the sinoatrial node cell activity and cytoskeleton protein β-tubulin of each group. Results Living cells of model group decreased significantly compared with normal group (P<0.01), and cytoskeleton proteinβ-tubulin cleavage significantly. Living cells of Tongyang Huoxue Recipe high, medium and low dose group were significantly higher than those in the model group (P<0.05), and β-tubulin structure remained more complete than the model group. Conclusion Tongyang Huoxue Recipe can inhibit the injury induced by ischemia reperfusion of sinoatrial node cells;the possible mechanism of Tongyang Huoxue Recipe in treating sick sinus syndrome is protecting activity and cytoskeleton proteinβ-tubulin of sinoatrial node cells.

RE: An Unusual Course of Right Coronary Artery Originating from Sinoatrial Node Artery

No abstract available.

Anatomic study of the right coronary artery in pigs: feature review in comparison with the human artery / Estudio anatómico de la arteria coronaria derecha en cerdos: revisión de sus características en comparación con la del humano

A few studies conducted on the morphology of coronary arteries in pigs emphasize the description of its course and number of branches. The objective of this study was to determine the anatomic expression of the right coronary artery (RCA) in pigs of commercial stock. One hundred and fifty eight hearts obtained from pigs destined to sacrifice were studied. The RCA were perfused with polyester resin (Palatal 85 percent and Styrene 15 percent) and then subjected to KOH infusion for 5 minutes to release the subepicardial fat. Diameters were measured and courses were evaluated. Results: The diameter of the RCA in its proximal portion was 3.85 mm (SD 0.75). The right artery of the cone originated from the RCA in 100 specimens (63.3 percent) and from the aorta (third coronary) in 8 specimens (5.1 percent). The posterior interventricular branch (PIB) reached the apex in the majority of the cases (49.3 percent). Its proximal diameter was 2.75 mm (SD 0.61). The sinoatrial node branch (SAB) and the atrioventricular node branch (AVNB) originated from the RCA in 100 percent of the specimens. The diameters of the SAB and AVNB were 1.1 mm (SD 0.30) and 1.16 mm (SD 0.30), respectively. The posterior right diagonal branch was not observed. There is an agreement with most prior studies with respect to both SAB and AVNB emerging from the RCA. Morphometric and qualitative knowledge of the RCA and its branches in pigs is relevant for the design of procedural and hemodynamic models.

Los escasos estudios realizados con relación a la morfología de las arterias coronarias en porcinos enfatizan en descripciones de sus trayectorias y número de ramas. El objetivo del estudio fue determinar la expresión anatómica de la arteria coronaria derecha (ACD) en cerdos de razas comerciales. Fueron estudiados 158 corazones extraídos de cerdos destinados al sacrificio. Las ACD fueron perfundidas con resina poliéster (Palatal 85 por ciento y Estireno15 por ciento) y posteriormente sometidas a infusión de KOH durante 5 minutos para liberar la grasa subepicárdica. Se midieron calibres y evaluaron trayectorias. El calibre de la ACD en su porción proximal fue 3,85 mm (DE 0,75). La arteria derecha del cono se originó de la ACD en 100 especímenes (92,6 por ciento) y de la aorta (tercera coronaria) en 8 (7,4 por ciento). La arteria interventricular posterior (AIP) alcanzó el ápex en la mayoría de los casos (49,3 por ciento.) Su calibre proximal fue 2,75 mm (DE 0,61). La rama del nodo sinusal (RNS) y la rama del nodo atrio ventricular (RNAV) se originaron de la ACD en el 100 por ciento de los especímenes. Los calibres de la RNS y RNAV fueron 1,1 mm (DE 0,30) y 1,16 mm (DE 0,30) respectivamente. No se observó rama posterolateral. Existe concordancia con la mayoría de estudios previos con relación a la emergencia desde la ACD de las ramas RNS y RNAV. El conocimiento morfométrico y cualitativo de la ACD y sus ramas en porcinos, es relevante para el diseño de modelos procedimentales y hemodinámicos.

Effects of dexmedetomidine on action potential in isolated rabbit sinoatrial node cells / 中华麻醉学杂志

Objective To evaluate the effects of dexmedetomidine on action potential in isolated rabbit sinoatrial node cells.Methods Twenty-four healthy New Zealand rabbits of both sexes,weighing 1.5-2.5 kg,were sacrificed.Their hearts were removed and sinoatrial nodes were dissected and placed in Tyrode solution.Sixty isolated sinoatrial nodes were randomly divided into 6 groups (n =10 each):control group (group C),0.5 ng/ml dexmedetomedine group (group D1),5.0 ng/ml dexmedetomedine group (group D2),dexmedetomidine 5.0 ng/ml + yohimbine 1 μmol/L (alpha 2-adrenoreceptor antagonist) group (group D2 + Y),dexmedetomidine 5.0 ng/ml + 2 mmol/L CsCl (blocker of pacemaker current) group (group D2 + C),and dexmedetomidine 50.0 ng/ml group (group D3).After perfusion with the Tyrode' s solution for 60 min,C group was perfused with Tyrode' s solution for another 40 min,D1-3 groups were perfused with Tyrode's solution cont(a)ining dexmedetomedine 0.5,5.0 and 50.0 ng/ml,respectively,for40 min,and D2 + Y and D2 + C groups were perfused with Tyrode' s solution containing 1 μmol/L yohimbine and 2 mmol/L CsCl,respectively,for 20 min,and then 5.0 ng/ml dexmedetomedine was added and sinoatrial nodes were perfused for 20 min.Maximal rate of depolarization (Vmax),amplitude of action potential (APA),action potential duration at 50％ and 90％ repolarization (APDso and APD90),velocity of diastolic (phase 4) depolarization (VDD),and rate of pacemaker firing (RPF) were recorded at 60 min of perfusion with Tyrode' s solution (T1),20 min of perfusion with yohimbine or CsCl (T2) and termination of perfusion with dexmedetomedine (T3).Results Compared with group C,APA,VDD and RPF were gradually decreased at T2,3 in groups D1-3 (P ＜ 0.05),and there was no significant difference in Vmax,APD50 and APD9o among C and D1-3 groups (P ＞ 0.05).VDD and RPF at T2 in group D2 + C and APA,VDD and RPF at T3 in groups D2 + Y and D2 + C were significantly lower than those at T1 (P ＜ 0.05).APA,VDD and RPF in group D2 + Y and APA in group D2 + C were significantly lower at T3 than at T2 (P ＜ 0.05).Conclusion Dexmedetomidine can decrease the sinoatrial node autorhythmicity in a concentration-dependent manner in rabbits,and the mechanism may be related to the inhibition of pacemaker current,but not alpha 2-adrenoreceptor.

IgG4-Related Sclerosing Disease Involving the Superior Vena Cava and the Atrial Septum of the Heart

A 55-year-old woman presented with frequent episodes of syncope due to sinus pauses. During ambulatory Holter monitoring, atrial fibrillation and first-degree atrioventricular nodal block were observed. Magnetic resonance imaging and CT scans showed a tumor-like mass from the superior vena cava to the right atrial septum. Open chest cardiac biopsy was performed. The tumor was composed of proliferating IgG4-positive plasma cells and lymphocytes with surrounding sclerosis. The patient was diagnosed with IgG4-related sclerosing disease. Because of frequent sinus pauses and syncope, a permanent pacemaker was implanted. The cardiac mass was inoperable, but it did not progress during the one-year follow-up.