Successful Implantation of Transvenous Pacing System via Persistent Left Superior Vena Cava and Coronary Sinus in Small Children

Transvenous pacemaker implantation tends to be difficult in the setting of a persistent left superior vena cava (SVC) and an absent or inaccessible right SVC. We report two small children in whom transvenous pacing leads were successfully inserted via a persistent left SVC. This technique was safe in our cases; however, favorable long-term result has yet to be demonstrated.     

Usefulness of a lead delivery system consisting of a fixed-shaped sheath and a lumenless bipolar lead in a patient with absent right and persistent left superior vena cava: A case report

We report the case of an 84-year-old female with symptomatic bradycardia due to a complete atrioventricular block, who carried absent right and persistent left superior vena cava (SVC). Implantation of a pacing lead, particularly within the right ventricle (RV) in a patient with this venous anomaly is accompanied by technical difficulties. However, the apparatus consisting of a fixed-curve sheath (Model C315-S10, Medtronic, Inc., Minneapolis, MN, USA) and a lumenless fixed-screw pacing lead (Model 3830, Medtronic), allowed a rapid delivery into the RV without any complications. By rotating the Model C315-S10 sheath in the counterclockwise direction in the right atrium, its tip faced the tricuspid orifice, advanced across the tricuspid valve and confronted the RV lower septum near the apex. Then the RV-lead was fixed with acceptable pacing and sensing parameters. Utilizing a lumenless pacing lead and a preformed sheath to deliver it is a novel approach that could be helpful in pacemaker implantation in patients with absent right and persistent left SVC.     

A linear ablating system in the left and right atrium: feasibility, catheter performance and clinical results

IntroductionWe describe the use of a ablating system to compartmentalise and regionally isolate the atria in paroxysmal and persistent atrial fibrillation (AF).Methods40 patients were studied, 25 paroxysmal AF and 14 persistent AF. One patient enrolled was later found to be in left atrial flutter and was excluded. The Cardima Revelation® TX catheter system with Intellitemp® Radiofrequency (RF) energy control device and a Medtronic Atakar® RF generator were used to place wide area circumferential ablations to achieve conduction block into the left and right sided pulmonary veins. Roof lines and mitral isthmus lines were also performed. In patients with persistent AF and in repeat procedures, right atrial compartmentalisation was performed with an anterior superior vena cava (SVC) to inferior vena cava (IVC) line and a septal SVC to IVC line.ResultsAt 6 months, 18 of the 39 patients were asymptomatic, 10 had improved symptoms and 22 were in sinus rhythm. In the paroxysmal group, 11 were asymptomatic, 7 had improved symptoms and 16 (64%) were in sinus rhythm. In the persistent group, 7 were asymptomatic, 3 had improved symptoms and 6 (43%) were in sinus rhythm. The total group AF burden was 37.8 ± 5.4 hrs pre-procedure and 23.1 ± 5.1 hrs at 6 months post procedure. Mean temperature, impedance and power recorded at each pole demonstrated effective power delivery at all poles. No catheter charring was observed, complication rates were comparable to standard AF ablation technique.ConclusionLinear ablation in the left and right atria to mimic Cox’s Maze is feasible and safe using this ablating system.     

4:2:1 conduction of an AF initiating trigger

A 44 year old male with idiopathic dilated cardiomyopathy was undergoing persistent atrial fibrillation (AF) ablation. Following antral ablation, AF terminated into a regular narrow complex rhythm. Earliest activation was mapped to a focus in the superior vena cava (SVC) which was conducted in a 2:1 ratio to the atria which in turn was conducted with 2:1 ratio to the ventricles, resulting in an unusual 4:2:1 conduction of the SVC tachycardia. 1:1 conduction of the SVC tachycardia to the atrium preceded initiation of AF. During AF, SVC tachycardia continued unperturbed. Sinus rhythm was restored following catheter ablation of the focus.     

Left superior vena cava, a remnant of embryological development

A 46-year-old Brugada syndrome patient underwent insertion of a dual-chamber implantable cardioverter- defibrillator (ICD), revealing a left-sided superior vena cava (SVC), (figure 1), running, characteristically, left from the sternum and flowing into the great cardiac vein. Following this course, the atrial lead was placed in the right atrium (RA) (figure 2, arrow, note dorsal position). The ventricular lead was inserted through the connecting anonymous vein between left and right SVC (figure 1, double arrow), into the right SVC and right ventricle (RV). The presence of a left superior vena cava results from the persistence of the embryonic left anterior cardinal vein. This anomaly is present in approximately 0.5% of the general population and in 3 to 5% of persons with other congenital heart defects, as established by autopsy.     

All is not lost, when lead goes in the wrong direction

Left sided superior vena cava (SVC) is an uncommon anomaly noted in the general population. It adds complexity to the procedure, when attempting to place pacing or defibrillator devices into the heart. Here we report a case where the leads were placed through the left sided SVC into the right sided chambers giving an interesting X-ray appearance.     

Adipokines identified as new downstream targets for adiponectin: lessons from adiponectin-overexpressing or -deficient mice

Adipokines play a central role in the pathogenesis of the metabolic syndrome. Among them, adiponectin (ApN), a master regulator of immune and fuel homeostasis, is decreased. Identifying downstream adipokines targeted by ApN may help in deciphering this syndrome. We have generated transgenic mice, allowing persistent and moderate overexpression of ApN (ApN-Overex) specifically in white adipose tissue (AT). We took advantage of this model to unravel the adipokine secretion profile triggered by ApN. AT was fractionated into adipocytes and stromal-vascular cells (SVC), which were cultured for 8 h. Profiling of secretory products by antibody arrays and subsequent ELISAs showed that the secretion of three proinflammatory factors (IL-17B, IL-21, TNFα) and three hematopoietic growth factors [GF; thrombopoietin and granulocyte (macrophage) colony-stimulating-factors] was reduced in adipocytes of ApN-Overex mice compared with wild-type mice. In the SVC of these mice, besides the hematopoietic GFs, the secretion of another GF (vascular endothelial GF receptor 1), two chemokines (RANTES and ICAM-1), and two proinflammatory factors (IL-6 and IL-12p70) was reduced as well. Only one cytokine, IL-1 receptor 4, was oversecreted by SVC of ApN-Overex mice, which may exhibit anti-inflammatory properties. Most of these changes in secretion were due to corresponding changes in mRNAs. A reverse profile of adipokine expression was observed in ApN-KO mice. In conclusion, ApN regulates in vivo the secretion of downstream adipokines, thereby inducing a shift of the immune balance in both adipocytes and SVC toward a less inflammatory phenotype. These downstream adipokines may be new therapeutic targets for the management of the metabolic syndrome.     

Persistent left superior vena cava as an incidental fnding in the introduction of a transient pacemaker: A case report

The persistent left superior vena cava is the most common venous anomaly in the systemic drainage in adults and tends to be asymptomatic. The persistent left superior vena cava causes rhythm disorders such as tachyarrhythmias or bradyarrhythmias. We report a case of persistent left superior vena cava diagnosed in a 53-year-old female patient admitted due to an acute coronary syndrome associated with unstable bradycardia. A transvenous peacemaker impressed the left atrium; therefore, a transthoracic echocardiogram was required to diagnose persistent left superior vena cava. The patient needed management with percutaneous intervention; she had an adequate evolution and subsequent discharge from the intensive care unit     

The likelihood of aggregation during protein renaturation can be assessed using the second virial coefficient

Protein aggregation is commonly observed during protein refolding. To better understand this phenomenon, the intermolecular interactions experienced by a protein during unfolding and refolding are inferred from second virial coefficient (SVC) measurements. It is accepted that a negative SVC is indicative of protein-protein interactions that are attractive, whereas a positive SVC indicates net repulsive interactions. Lysozyme denatured and reduced in guanidinium hydrochloride exhibited a decreasing SVC as the denaturant was diluted, and the SVC approached zero at approximately 3 M GdnHCl. Further dilution of denaturant to renaturation conditions (1.25 M GdnHCl) led to a negative SVC, and significant protein aggregation was observed. The inclusion of 500 mM L-arginine in the renaturation buffer shifted the SVC to positive and suppressed aggregation, thereby increasing refolding yield. The formation of mixed disulfides in the denatured state prior to refolding also increased protein solubility and suppressed aggregation, even without the use of L-arginine. Again, the suppression of aggregation was shown to be caused by a shift from attractive to repulsive intermolecular interactions as reflected in a shift from a negative to a positive SVC value. To the best of our knowledge, this is the first time that SVC data have been reported for renaturation studies. We believe this technique will aid in our understanding of how certain conditions promote renaturation and increase protein solubility, thereby suppressing aggregation. SVC measurements provide a useful link, for protein folding and aggregation, between empirical observation and thermodynamics.     

The characteristics of action potential and nonselec-tive cation current of cardiomyocytes in rabbit superior vena cava

As a special focus in initiating and maintaining atrial fibrillation (AF), cardiomyocytes in superior vena cava (SVC) have distinctive electrophysiological characters. In this study, we found that comparing with the right atrial (RA) cardiomyoctyes, the SVC cardiomyoctyes had longer APD90 at the different basic cycle lengths; the conduction block could be observed on both RA and SVC cardiomyoctyes. A few of SVC cardiomyoctyes showed slow response action potentials with automatic activity and some others showed early afterdepolarization (EAD) spontaneously. Further more, we found that there are nonselective cation current (INs) in both SVC and RA cardiomyocytes. The peak density of INs in SVC cardiomyocytes was smaller than that in RA cardiomyocytes. Removal of extracellular divalent cation and glucose could increase INs in SVC cardiomyocytes. The agonist or the antagonist of INs may in-crease or decrease APD. To sum up, some SVC cardiomyocytes possess the ability of spontaneous activity; the difference of transmembrane action potentials between SVC and RA cardiomyocytes is partly because of the different density of INs between them; the agonist or the antagonist of INs can in-crease or decrease APD leading to the enhancement or reduction of EAD genesis in SVC cardiomyo-cytes. INs in rabbit myocytes is fairly similar to TRPC3 current in electrophysiological property, which might play an important role in the mechanisms of AF.     

Phrenic nerve injury after catheter ablation of atrial fibrillation

Phrenic Nerve Injury (PNI) has been well studied by cardiac surgeons. More recently it has been recognized as a potential complication of catheter ablation with a prevalence of 0.11 to 0.48 % after atrial fibrillation (AF) ablation. This review will focus on PNI after AF ablation. Anatomical studies have shown a close relationship between the right phrenic nerve and it's proximity to the superior vena cava (SVC), and the antero-inferior part of the right superior pulmonary vein (RSPV). In addition, the proximity of the left phrenic nerve to the left atrial appendage has been well established. Independent of the type of ablation catheter (4 mm, 8 mm, irrigated tip, balloon) or energy source used (radiofrequency (RF), ultrasound, cryothermia, and laser); the risk of PNI exists during ablation at the critical areas listed above. Although up to thirty-one percent of patients with PNI after AF ablation remain asymptomatic, dyspnea remain the cardinal symptom and is present in all symptomatic patients. Despite the theoretical risk for significant adverse effect on functional status and quality of life, short-term outcomes from published studies appear favorable with 81% of patients with PNI having a complete recovery after 7 +/- 7 months. CONCLUSION: Existing studies have described PNI as an uncommon but avoidable complication in patients undergoing pulmonary vein isolation for AF. Prior to ablation at the SVC, antero-inferior RSPV ostium or the left atrial appendage, pacing should be performed before energy delivery. If phrenic nerve capture is documented, energy delivery should be avoided at this site. Electrophysiologist's vigilance as well as pacing prior to ablation at high risk sites in close proximity to the phrenic nerve are the currently available tools to avoid the complication of PNI.     

β-Adrenergic stimulation induces pro-arrhythmic activity in the caval vein myocardial tissue

Electrical activity of the right superior vena cava (SVC) is considered as a source of the atrial fibrillation. We have shown that bioelectrical properties of the SVC myocardium differ from those of the working atrial myocardium. Electrically evoked action potential duration in SVC is significantly shorter, the resting membrane potential in both stimulated and quiescent SVC preparations is significantly more positive than in atria. Activation of β-adrenoreceptors in SVC myocardium leads to a series of action potentials, and this process depends on protein kinase A. Probably, β-adrenergic stimulation enhances SVC arrhythmogenesis in vivo.     

Estimating the potential refolding yield of recombinant proteins expressed as inclusion bodies

Recombinant protein production in bacteria is efficient except that insoluble inclusion bodies form when some gene sequences are expressed. Such proteins must undergo renaturation, which is an inefficient process due to protein aggregation on dilution from concentrated denaturant. In this study, the protein-protein interactions of eight distinct inclusion-body proteins are quantified, in different solution conditions, by measurement of protein second virial coefficients (SVCs). Protein solubility is shown to decrease as the SVC is reduced (i.e., as protein interactions become more attractive). Plots of SVC versus denaturant concentration demonstrate two clear groupings of proteins: a more aggregative group and a group having higher SVC and better solubility. A correlation of the measured SVC with protein molecular weight and hydropathicity, that is able to predict which group each of the eight proteins falls into, is presented. The inclusion of additives known to inhibit aggregation during renaturation improves solubility and increases the SVC of both protein groups. Furthermore, an estimate of maximum refolding yield (or solubility) using high-performance liquid chromatography was obtained for each protein tested, under different environmental conditions, enabling a relationship between "yield" and SVC to be demonstrated. Combined, the results enable an approximate estimation of the maximum refolding yield that is attainable for each of the eight proteins examined, under a selected chemical environment. Although the correlations must be tested with a far larger set of protein sequences, this work represents a significant move beyond empirical approaches for optimizing renaturation conditions. The approach moves toward the ideal of predicting maximum refolding yield using simple bioinformatic metrics that can be estimated from the gene sequence. Such a capability could potentially "screen," in silico, those sequences suitable for expression in bacteria from those that must be expressed in more complex hosts.     

The characteristics of action potential and nonselective cation current of cardiomyocytes in rabbit superior vena cava

As a special focus in initiating and maintaining atrial fibrillation (AF), cardiomyocytes in superior vena cava (SVC) have distinctive electrophysiological characters. In this study, we found that comparing with the right atrial (RA) cardiomyoctyes, the SVC cardiomyoctyes had longer APD₉₀ at the different basic cycle lengths; the conduction block could be observed on both RA and SVC cardiomyoctyes. A few of SVC cardiomyoctyes showed slow response action potentials with automatic activity and some others showed early afterdepolarization (EAD) spontaneously. Further more, we found that there are nonselective cation current (I _Ns) in both SVC and RA cardiomyocytes. The peak density of I _Ns in SVC cardiomyocytes was smaller than that in RA cardiomyocytes. Removal of extracellular divalent cation and glucose could increase I _Ns in SVC cardiomyocytes. The agonist or the antagonist of I _Ns may increase or decrease APD. To sum up, some SVC cardiomyocytes possess the ability of spontaneous activity; the difference of transmembrane action potentials between SVC and RA cardiomyocytes is partly because of the different density of I _Ns between them; the agonist or the antagonist of I _Ns can increase or decrease APD leading to the enhancement or reduction of EAD genesis in SVC cardiomyocytes. I _Ns in rabbit myocytes is fairly similar to TRPC3 current in electrophysiological property, which might play an important role in the mechanisms of AF.     

Doppler flow spectra of the superior vena cava in a rat model of chronic pulmonary hypertension

The aim of this study was to explore the changes of the Doppler flow spectra of the superior vena cava (SVC) in a rat model of chronic pulmonary hypertension (PH). Thirty-two rats were injected with monocrotaline (MCT) to establish a model of chronic PH. Eight rats from the control group had a sham operation by injecting Dulbecco's phosphate-buffered solution. Serial echocardiographic parameters of the SVC were analysed four weeks after treating with MCT or placebo, and the relationship was analysed between the Doppler flow spectra of SVC and the pulmonary arterial systolic pressure (PASP). PH models were successfully established in 29 rats. The right ventricular systolic pressure, mean pulmonary arterial pressure and PASP in the PH group were significantly higher than those in the sham group at 28 days (P < 0.001). The ratios of SVC maximum reverse peak flow velocity/maximum systolic peak flow velocity (VAr/VS) and maximum reverse peak velocity time integral/maximum systolic peak velocity time integral (VTIAr/VTIS) increased significantly (P < 0.05) after MCT injection. These results demonstrate that echocardiography can be used to monitor the haemodynamic changes in SVC in MCT-induced chronic PH rat models. The ratios of VAr/VS and VTIAr/VTIS may be sensitive indices for evaluating PH.     

Wolff-Parkinson-White syndrome with an unroofed coronary sinus without persistent left superior vena cava treated with catheter cryoablation

Coronary sinus anomalies are rare congenital defects which are usually coexistent with a persistent left superior vena cava and may be associated with cardiac arrhythmias. We report an unroofed coronary sinus without persistent left superior vena cava diagnosed during a catheter ablation procedure for Wolff-Parkinson-White syndrome. Diagnostic and therapeutic options and outcomes are discussed. This condition is of relevance to electrophysiologists performing catheter-based procedures, as well as cardiologists implanting coronary sinus pacing leads, who may encounter this anomaly in their practice.     

Implantation of a resynchronization implantable cardioverter defibrillator in a patient with persistent left superior vena cava

Implantation of resynchronization implantable cardioverter defibrillator was performed in a patient with persistent left superior vena cava. A dual coil defibrillation lead was inserted in the right ventricle apex via a small innominate vein. Left ventricular and atrial leads were implanted through persistent left superior vena cava. Left ventricular lead was easily implanted into the postero lateral vein. Pacing thresholds and sensing values were excellent and remained stable at 18 months follow-up.Presence of persistent left superior vena cava generally makes transvenous lead implantation difficult. However when a favorable coronary sinus anatomy is also present, it may facilitate left ventricular lead positioning in the coronary sinus branches.     

Refractoriness of the sheep superior vena cava myocardial sleeve

The cardiomyocytes in the superior vena cava (SVC) myocardial sleeve have distinct action potentials and ionic current profiles, but the refractoriness of these cells has not been reported. Using standard intracellular microelectrode techniques, we demonstrated in sheep that the effective refractory period (ERP) of the cardiomyocytes in the SVC (114.7 +/- 6.5 ms) is shorter than that in the inferior vena cava (IVC) (166.7 +/- 6.2 ms), right atrial free wall (RAFW) (201.0 +/- 6.0 ms) and right atrial appendage (RAA) (203.1 +/- 5.8 ms) (P < 0.05). The right atrial cardiomyocyte ERP was heterogeneously shortened by acetylcholine, a muscarinic type 2 receptor (M(2)R) agonist. After perfusion with 15 microM acetylcholine, the shortest ERP occurred in the SVC (the ERP in the SVC, IVC, RAFW and RAA was 53.6 +/- 2.7, 98.9 +/- 2.2, 121.8 +/- 6.0 and 109.7 +/- 5.1 ms, respectively; P < 0.05). Carbachol (1 microM), another M(2)R agonist, produced a similar effect as acetylcholine. Furthermore, we used methoctramine, a M(2)R blocker, 4-DAMP, a muscarinic type 3 receptor (M(3)R) blocker, and tropicamide, a muscarinic type 4 receptor (M(4)R) blocker to inhibit the acetylcholine-induced ERP shortening of SVC cardiomyocytes, and found that the 50% inhibitory concentration for methoctramine, 4-DAMP and tropicamide was 5.91, 45.72 and 80.34 nM, respectively. Therefore, we conclude that the sheep SVC myocardial sleeve is a unique electrophysiological region of the right atrium with the shortest ERP both under physiological condition and under cholinergic agonist stimulation. M(2)R might play a major role in the response of the SVC myocardial sleeve to parasympathetic nerve tone. The association between the distinct refractoriness in SVC and atrial fibrillation originating from the region deserves further investigation.     

An unusual presentation with persistent left superior vena cava

Persistent left superior vena cava (LSVC) is the most common congenital systemic venous anomaly, which may give rise to several problems. We present a case in which a persistent LSVC was an unsuspected finding. A 70-year-old male presented with intracerebral empyema which may have been caused by venous septic emboli from the left arm and facilitated by a persistent LSVC draining directly into the left atrium. Visualisation of the anomaly was performed with echocardiography and magnetic resonance angiography. In addition we present a brief review of the literature concerning this disorder.     

An optimized live bacterial delivery vehicle safely and efficaciously delivers bacterially transcribed therapeutic nucleic acids

There is an unmet need for delivery platforms that realize the full potential of next-generation nucleic acid therapeutics. The in vivo usefulness of current delivery systems is limited by numerous weaknesses, including poor targeting specificity, inefficient access to target cell cytoplasm, immune activation, off-target effects, small therapeutic windows, limited genetic encoding and cargo capacity, and manufacturing challenges. Here we characterize the safety and efficacy of a delivery platform comprising engineered live, tissue-targeting, non-pathogenic bacteria (Escherichia coli SVC1) for intracellular cargo delivery. SVC1 bacteria are engineered to specifically bind to epithelial cells via a surface-expressed targeting ligand, to allow escape of their cargo from the phagosome, and to have minimal immunogenicity. We describe SVC1's ability to deliver short hairpin RNA (shRNA), localized SVC1 administration to various tissues, and its minimal immunogenicity. To validate the therapeutic potential of SVC1, we used it to deliver influenza-targeting antiviral shRNAs to respiratory tissues in vivo. These data are the first to establish the safety and efficacy of this bacteria-based delivery platform for use in multiple tissue types and as an antiviral in the mammalian respiratory tract. We expect that this optimized delivery platform will enable a variety of advanced therapeutic approaches.