Abstract 16594: Disruption of Caveolae-Confined Phosphorylation of Ryanodine Receptors Promotes Ca 2+ Handling Abnormalities and Arrhythmogenesis in Mouse Atrial Myocytes

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Roman Medvedev ◽  
Di Lang ◽  
Alexey Glukhov
Keyword(s):  
Protein Kinase ◽  
Superior Vena ◽  
Ryanodine Receptors ◽  
Vena Cava ◽  
Chronic Atrial Fibrillation ◽  
Right Atrial ◽  
Structural Protein ◽  
Crista Terminalis ◽  
Triggered Activity ◽  
Delayed Afterdepolarizations

Rationale: Chronic atrial fibrillation has been linked to ectopic triggered activity driven by delayed afterdepolarizations in response to sarcoplasmic reticulum Ca 2+ leak from certain areas in atria. These activities were associated with hyperphosphorylated ryanodine receptors (RyRs), while the underlying mechanisms remain uncertain. Here, we hypothesized that mouse atria have areas with lower transversal-axial tubule system (TATS) organization, where phosphorylation of RyRs is mainly confines by caveolae nanodomains and might be firstly disturbed in disease conditions. Methods and results: In wild type (WT) mouse intact atria stained with RH-237, we found that myocytes located in the intercaval region (ICR, between the superior vena cava and atrioventricular junction and between the crista terminalis and interatrial septum) have a significantly less density of TATS than right atrial appendage (RAA) myocytes: 5.7±0.4% in ICR vs. 13.4±0.9% in RAA, P<0.01. Also an elevated frequency of spontaneous Ca 2+ sparks was observed in myocytes isolated from ICR vs. RAA (12.5±2.6 vs. 1.5±0.3 sparks/μm/s, P<0.01). ICR myocytes isolated from mice with a cardiac-specific knockout of the main structural protein of caveolae, caveolin-3, showed significant increase of Ca 2+ sparks frequency as compared to WT (27.3±4.1 sparks/μm/s, P<0.01). Immunofluorescence staining of RyRs, phosphorylated at protein kinase A/ Ca 2+ /calmodulin-dependent protein kinase-II phosphorylation sites: Ser 2808 -RyR and Ser 2814 -RyR, showed predominant subsarcolemmal localization, with a high co-localization with caveolin-3, in ICR and RAA cells. Myocytes isolated from caveolin-3 knockout mice showed extension of both Ser 2808- RyR and Ser 2808- RyR to whole-cell wide striated pattern in ICR, but not RAA. This redistribution was associated with development of delayed afterdepolarizations in ICR but not RAA cells. Conclusions: Our findings demonstrate that in ICR in mouse atria, caveolae form functional, spatially-confined cAMP nanodomains and control localized RyR phosphorylation. Disruption of caveolae structures, seen in various pathologies, may lead to hyperphosphorylation of RyRs promoting Ca 2+ handling abnormalities and arrhythmogenic triggered activity.

Region-specific distribution of transversal-axial tubule system organization underlies heterogeneity of calcium dynamics in the right atrium

2021 ◽  
Author(s):  
Di Lang ◽  
Roman Y. Medvedev ◽  
Lucas Ratajczyk ◽  
Jingjing Zheng ◽  
Xiaoyu Yuan ◽  
...  
Keyword(s):  
Superior Vena ◽  
Vena Cava ◽  
Confocal Imaging ◽  
Right Atrial ◽  
Atrial Remodeling ◽  
Atrial Myocardium ◽  
Healthy Human ◽  
Crista Terminalis ◽  
Specific Distribution ◽  
The Right

The atrial myocardium demonstrates the highly heterogeneous organization of the transversal-axial tubule system (TATS), while its anatomical distribution and region-specific impact on Ca2+ dynamics remain unknown. We developed a novel method for high-resolution confocal imaging of TATS in intact live mouse atrial myocardium and applied a Matlab-based computational algorithm for the automated analysis of TATS integrity. We observed a 2-fold higher (P<0.01) TATS density in the right atrial appendage (RAA) than in the inter-caval region (ICR, the anatomical region between the superior vena cava and atrioventricular junction and between the crista terminalis and inter-atrial septum). While RAA predominantly consisted of well-tubulated myocytes, ICR showed partially tubulated/untubulated cells. Similar TATS distribution was also observed in healthy human atrial myocardium sections. In both mouse atrial preparations and isolated mouse atrial myocytes, we observed a strong anatomical correlation between TATS distribution and Ca2+ transient synchronization and rise-up time. This region-specific difference in Ca2+ transient morphology disappeared after formamide-induced detubulation. ICR myocytes showed a prolonged action potential duration at 80% of repolarization as well as a significantly lower expression of RyR2 and Cav1.2 proteins, but similar levels of NCX1 and Cav1.3 compared to RAA tissue. Our findings provide a detailed characterization of the region-specific distribution of TATS in mouse and human atrial myocardium highlighting the structural foundation for anatomical heterogeneity of Ca2+ dynamics and contractility in the atria. These results could indicate different roles of TATS in Ca2+ signaling at distinct anatomical regions of the atria and provide mechanistic insight into pathological atrial remodeling.

Single-Patch Fold-Back Technique for Augmentation of the Superior Vena Cava in Sinus Venosus Atrial Septal Defect Associated with Partial Anomalous Pulmonary Venous Return

2015 ◽  
Vol 17 (6) ◽  
pp. 282
Author(s):  
Suguru Ohira ◽  
Kiyoshi Doi ◽  
Takeshi Nakamura ◽  
Hitoshi Yaku
Keyword(s):  
Atrial Septal Defect ◽  
Superior Vena Cava ◽  
Septal Defect ◽  
Venous Return ◽  
Superior Vena ◽  
Pulmonary Veins ◽  
Vena Cava ◽  
Sinus Venosus ◽  
Right Atrial ◽  
Anomalous Pulmonary Venous Return

Sinus venosus atrial septal defect (ASD) is usually associated with partial anomalous pulmonary venous return (PAPVR) of the right pulmonary veins to the superior vena cava (SVC), or to the SVC-right atrial junction. Standard procedure for repair of this defect is a patch roofing of the sinus venosus ASD and rerouting of pulmonary veins. However, the presence of SVC stenosis is a complication of this technique, and SVC augmentation is necessary in some cases. We present a simple technique for concomitant closure of sinus venosus ASD associated with PAPVR and augmentation of the SVC with a single autologous pericardial patch.

Increased cardiac output following occlusion of the descending thoracic aorta in dogs

1982 ◽  
Vol 243 (1) ◽  
pp. R152-R158 ◽  
Author(s):  
J. K. Stene ◽  
B. Burns ◽  
S. Permutt ◽  
P. Caldini ◽  
M. Shanoff
Keyword(s):  
Cardiac Output ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Thoracic Aorta ◽  
Vascular System ◽  
Superior Vena ◽  
Vena Cava ◽  
Right Atrial ◽  
Mean Systemic Pressure ◽  
Extracorporeal Bypass

Occlusion of the thoracic aorta (AO) in dogs with a constant volume right ventricular extracorporeal bypass increased cardiac output (Q) by 43% and mean arterial pressure by 46%, while mean systemic pressure (MSP) was unchanged. We compared AO with occlusion of the brachiocephalic and left subclavian arteries (BSO) which decreased cardiac output by 5%, increased mean arterial pressure by 32%, and increased MSP by 11%. We feel these results confirm that AO elevates preload by transferring blood volume from the splanchnic veins to the vascular system drained by the superior vena cava. If the heart is competent to keep right arterial pressure at or near zero, this increase in preload will elevate Q above control levels. Comparing our data with results of other authors who have not controlled right atrial pressure, emphasizes the importance of a competent right ventricle in allowing venous return to determine Q.

Influence of right atrial stretch on plasma renin activity in the conscious rat

1987 ◽  
Vol 65 (2) ◽  
pp. 257-259 ◽  
Author(s):  
Susan Kaufman
Keyword(s):  
Plasma Renin Activity ◽  
Superior Vena ◽  
Vena Cava ◽  
Extracellular Fluid ◽  
Plasma Renin ◽  
Renin Activity ◽  
Right Atrial ◽  
Balloon Inflation ◽  
Conscious Rat ◽  
Basal Plasma

Rats were prepared with inflatable balloons at the superior vena cava – right atrium junction. After recovery 1 week later, when blood was taken from conscious, normovolaemic animals plasma renin activity was found not to be influenced by right atrial stretch. Plasma renin activity was then measured in rats in which an extracellular fluid deficit had been produced by peritoneal dialysis against a hyperoncotic, isotonic solution. Although basal plasma renin activity was elevated (6.8 ± 0.9 from 1.5 ± 0.2 ng∙mL∙h, n = 19), no depression was observed in the experimental group after 15 or 90 min of balloon inflation. In rats pretreated with isoprenaline (10 μg/kg body wt.) plasma renin activity was also increased over basal levels, but again balloon inflation caused no reduction in plasma renin activity. It would appear that right atrial stretch has little, if any, influence on renin release in the conscious rat.

Thoracic vein ablation terminates chronic atrial fibrillation in dogs

2004 ◽  
Vol 286 (6) ◽  
pp. H2072-H2077 ◽  
Author(s):  
Angela M. Park ◽  
Chung-Chuan Chou ◽  
Paul C. Drury ◽  
Yuji Okuyama ◽  
Anish Peter ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Superior Vena Cava ◽  
Superior Vena ◽  
Vena Cava ◽  
Chronic Atrial Fibrillation ◽  
Atrial Pacing ◽  
Bipolar Electrodes ◽  
Cycle Lengths ◽  
Activation Cycle

The thoracic vein hypothesis of chronic atrial fibrillation (AF) posits that rapid, repetitive activations from muscle sleeves within thoracic veins underlie the mechanism of sustained AF. If this is so, thoracic vein ablation should terminate sustained AF and prevent its reinduction. Six female mongrel dogs underwent chronic pulmonary vein (PV) pacing at 20 Hz to induce sustained (>48 h) AF. Bipolar electrodes were used to record from the atria and thoracic veins, including the vein of Marshall, four PVs, and the superior vena cava. Radio frequency (RF) application was applied around the PVs and superior vena cava and along the vein of Marshall until electrical activity was eliminated. Computerized mapping (1,792 electrodes, 1 mm resolution) was also performed. Sustained AF was induced in 30.6 ± 6.5 days, and ablation was done 17.3 ± 8.5 days afterward. Before ablation, the PVs had shorter activation cycle lengths than the atria, and rapid, repetitive activations were observed in the PVs. All dogs converted to sinus rhythm during ( n = 4 dogs) or within 90 min of completion of RF ablation. Rapid atrial pacing afterward induced only nonsustained (<60 s) AF in all dogs. Average AF cycle lengths after reinduction were significantly ( P = 0.01) longer (183 ± 31.5 ms) than baseline (106 ± 16.2 ms). There were no activation cycle length gradients after RF application. We conclude that thoracic vein ablation converts canine sustained AF into sinus rhythm and prevents the reinduction of sustained AF. These findings suggest that thoracic veins are important in the maintenance of AF in dogs.

scholarly journals Recurrent cardiac hydatid cyst located near the root of the superior vena cava and the interatrial septum: a case report

2022 ◽  
pp. 1-4
Author(s):  
Redha Lakehal ◽  
Farid Aymer ◽  
Soumaya Bendjaballah ◽  
Rabah Daoud ◽  
Khaled Khacha ◽  
...  
Keyword(s):  
Hydatid Cyst ◽  
Facial Paralysis ◽  
Superior Vena Cava ◽  
Superior Vena ◽  
Vena Cava ◽  
Lower Lobe ◽  
Lateral Wall ◽  
Right Atrial ◽  
Risk Of Rupture ◽  
The Right

Introduction: Cardiac localization of hydatid disease is rare (<3%) even in endemic countries. Affection characterized by a long functional tolerance and a large clinical and paraclinical polymorphism. Serious cardiac hydatitosis because of the risk of rupture requiring urgent surgery. The diagnosis is based on serology and echocardiography. The aim of this work is to show a case of recurrent cardiac hydatid cyst discovered incidentally during a facial paralysis assessment. Methods: We report the observation of a 26-year-old woman operated on in 2012 for pericardial hydatid cyst presenting a cardiac hydatid cyst located near the abutment of the SCV discovered incidentally during an exploration for left facial paralysis: NYHA stage II dyspnea. Chest x-ray: CTI at 0.48. ECG: RSR. Echocardiography: Image of cystic appearance at the level of the abutment of the SVC. SAPP: 38 mmhg, EF: 65%. Thoracic scan: 30/27 mm cardiac hydatid cyst bulging the lateral wall of the right atrium and the trunk of the right pulmonary artery with fissured cardiac hydatid cyst of the apical segment of the right lung of the right lower lobe with multiple bilateral intra parenchymal and sub pleural nodules. The patient was operated on under CPB. Intraoperative exploration: Presence of a hard and whitish mass, about 03 / 03cm developed in the full right atrial wall opposite the entrance to the superior vena cava. Procedure: Resection of the mass removing the roof of the LA, the AIS and the wall of the RA with reconstruction of the roof of the RA by patch in Dacron and reconstruction of the IAS and the wall of the RA by a single patch in Dacron. Results: The postoperative suites were simple. Conclusion: The hydatid cyst is still a real endemic in Algeria, the cardiac location is rare but serious and can constitute a real surgical emergency, hence the importance of prevention. Keywords: Hydatid cyst of the heart; Recurrence; Surgery; Cardiopulmonary Bypass; Prevention

Central Venous Catheter Complications

PEDIATRICS ◽  
1983 ◽  
Vol 71 (5) ◽  
pp. 865-866
Author(s):  
JACK L. DOLCOURT ◽  
CARL L. BOSE
Keyword(s):  
Superior Vena Cava Syndrome ◽  
Superior Vena ◽  
Vena Cava ◽  
Clinical Signs ◽  
Venous Catheter ◽  
Upper Body ◽  
Right Atrial ◽  
Catheter Complications ◽  
Vena Cava Syndrome ◽  
Central Venous Catheter Complications

In Reply.— We thank Hoelzer and L'Hommedieu for their comments and for pointing out that subclavian catheters are capable of lasting as long as the percutaneously placed central Silastic catheter (PCSC).1,2 The median duration for PCSC usage in our series3 was 21 days. For us, the diagnosis of superior vena cava syndrome is only suspected in the presence of differential upper body edema. The diagnosis of right atrial thrombosis is not likely to be made by us without clinical signs of venous obstruction as echocardiograms are not routinely performed.

Inotropic, chronotropic, and dromotropic effects mediated via parasympathetic ganglia in the dog heart

2000 ◽  
Vol 279 (3) ◽  
pp. H1201-H1207 ◽  
Author(s):  
Masato Tsuboi ◽  
Yasuyuki Furukawa ◽  
Koichi Nakajima ◽  
Fumio Kurogouchi ◽  
Shigetoshi Chiba
Keyword(s):  
Superior Vena ◽  
Vena Cava ◽  
Contractile Force ◽  
Right Atrial ◽  
Fat Pad ◽  
Parasympathetic Ganglia ◽  
Dog Heart ◽  
Parasympathetic Nerves ◽  
Av Conduction ◽  
Stimulation Of

Some parasympathetic ganglionic cells are located in the epicardial fat pad between the medial superior vena cava and the aortic root (SVC-Ao fat pad) of the dog. We investigated whether the ganglionic cells in the SVC-Ao fat pad control the right atrial contractile force, sinus cycle length (SCL), and atrioventricular (AV) conduction in the autonomically decentralized heart of the anesthetized dog. Stimulation of both sides of the cervical vagal complexes (CVS) decreased right atrial contractile force, increased SCL, and prolonged AV interval. Stimulation of the rate-related parasympathetic nerves to the sinoatrial (SA) node (SAPS) increased SCL and decreased atrial contractile force. Stimulation of the AV conduction-related parasympathetic nerves to the AV node prolonged AV interval. Trimethaphan, a ganglionic nicotinic receptor blocker, injected into the SVC-Ao fat pad attenuated the negative inotropic, chronotropic, and dromotropic responses to CVS by 33∼37%. On the other hand, lidocaine, a sodium channel blocker, injected into the SVC-Ao fat pad almost totally inhibited the inotropic and chronotropic responses to CVS and partly inhibited the dromotropic one. Lidocaine or trimethaphan injected into the SAPS locus abolished the inotropic responses to SAPS, but it partly attenuated those to CVS, although these treatments abolished the chronotropic responses to SAPS or CVS. These results suggest that parasympathetic ganglionic cells in the SVC-Ao fat pad, differing from those in SA and AV fat pads, nonselectively control the atrial contractile force, SCL, and AV conduction partially in the dog heart.

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