Transvenous ICD Implantation into a Coronary Sinus Branch: A Safe and Feasible Alternative to Deliver ICD after Tricuspid Valve Reconstruction.

Significant lead-induced tricuspid regurgitation after cardiovascular implantable electronic devices is not uncommon. Absolute or relative contraindications to place the lead in the right ventricle after tricuspid valve (TV) surgery still remains a challenge. We report about successful lead extraction followed by transvenous implantable cardioverter defibrillator lead placement in the side branches of coronary sinus after TV reconstruction. Furthermore, we discuss therapeutic options to deliver concomitant anti-bradycardia therapy, technical pitfalls, and surgical approaches.

Epicardial catheter ablation for ventricular tachycardia on uninterrupted warfarin: A safe approach for those with a strong indication for peri-procedural anticoagulation?

BACKGROUND: Current guidelines for epicardial catheter ablation for ventricular tachycardia (VT) advocate that epicardial access is avoided in anticoagulated patients and should be performed prior to heparinisation. Recent studies have shown that epicardial access may be safe in heparinised patients. However, no data exist for patients on oral anticoagulants. We investigated the safety of obtaining epicardial access on uninterrupted warfarin. METHODS: A prospective registry of patients undergoing epicardial VT ablation over two years was analysed. Consecutive patients in whom epicardial access was attempted were included. All patients were heparinised prior to epicardial access with a target activated clotting time (ACT) of 300-350s. Patients who had procedures performed on uninterrupted warfarin (in addition to heparin) were compared to those not taking an oral anticoagulant. RESULTS: 46 patients were included of which 13 were taking warfarin. There was no significant difference in clinical and procedural characteristics (except INR and AF) between the two groups. Epicardial access was achieved in all patients. There were no deaths and no patients required surgery. A higher proportion of patients in the warfarin group had a drop in haemoglobin of >2g/dL compared to the no-warfarin group (38.5% versus 27.3%, p=0.74) and delayed pericardial drain removal (7.8% versus 3.03%, p=0.47). There was no difference in overall procedural complication rate. No patients required warfarin reversal or blood transfusion. CONCLUSION: Epicardial access can be achieved safely and effectively in patients' anticoagulated with warfarin and heparinised with therapeutic ACT. This may be an attractive option for patients with a high stroke risk.

Amiodarone inhibits arterial thrombus formation and tissue factor translation.

BACKGROUND: In patients with coronary artery disease and reduced ejection fraction, amiodarone reduces mortality by decreasing sudden death. Because the latter may be triggered by coronary artery thrombosis as much as ventricular arrhythmias, amiodarone might interfere with tissue factor (TF) expression and thrombus formation. METHODS AND RESULTS: Clinically relevant plasma concentrations of amiodarone reduced TF activity and impaired carotid artery thrombus formation in a mouse photochemical injury model in vivo. PTT, aPTT, and tail bleeding time were not affected; platelet number was slightly decreased. In human endothelial and vascular smooth muscle cells, amiodarone inhibited tumor necrosis factor (TNF)-alpha and thrombin-induced TF expression as well as surface activity. Amiodarone lacking iodine and the main metabolite of amiodarone, N-monodesethylamiodarone, inhibited TF expression. Amiodarone did not affect mitogen-activated protein kinase activation, TF mRNA expression, and TF protein degradation. Metabolic labeling confirmed that amiodarone inhibited TF protein translation. CONCLUSIONS: Amiodarone impairs thrombus formation in vivo; in line with this, it inhibits TF protein expression and surface activity in human vascular cells. These pleiotropic actions occur within the range of amiodarone concentrations measured in patients, and thus may account at least in part for its beneficial effects in patients with coronary artery disease.

Electric chips for rapid detection and quantification of nucleic acids.

A silicon chip-based electric detector coupled to bead-based sandwich hybridization (BBSH) is presented as an approach to perform rapid analysis of specific nucleic acids. A microfluidic platform incorporating paramagnetic beads with immobilized capture probes is used for the bio-recognition steps. The protocol involves simultaneous sandwich hybridization of a single-stranded nucleic acid target with the capture probe on the beads and with a detection probe in the reaction solution, followed by enzyme labeling of the detection probe, enzymatic reaction, and finally, potentiometric measurement of the enzyme product at the chip surface. Anti-DIG-alkaline phosphatase conjugate was used for the enzyme labeling of the DIG-labeled detection probe. p-Aminophenol phosphate (pAPP) was used as a substrate. The enzyme reaction product, p-aminophenol (pAP), is oxidized at the anode of the chip to quinoneimine that is reduced back to pAP at the cathode. The cycling oxidation and reduction of these compounds result in a current producing a characteristic signal that can be related to the concentration of the analyte. The performance of the different steps in the assay was characterized using in vitro synthesized RNA oligonucleotides and then the instrument was used for analysis of 16S rRNA in Escherichia coli extract. The assay time depends on the sensitivity required. Artificial RNA target and 16S rRNA, in amounts ranging from 10(11) to 10(10) molecules, were assayed within 25 min and 4 h, respectively.

Role of the general stress response during strong overexpression of a heterologous gene in Escherichia coli.

The strong overexpression of heterologous genes in Escherichia coli often leads to inhibition of cell growth, ribosome destruction, loss of culturability, and induction of stress responses, such as a heat shock-like response. Here we demonstrate that the general stress response, which is connected to the stress response regulator sigmas (sigma38, rpoS gene product), is suppressed during strong overproduction of a heterologous alpha-glucosidase. The mRNA levels of the rpoS and osmY stress genes drastically decrease after induction of the strong overexpression system. It is shown that an rpoS mutation causes a significant loss of cell viability after induction of the expression system. Furthermore, it is demonstrated that an E. coli c/pP mutant, which could be suggested to improve heterologous protein production, is not a good production host if a tac-promoter is used to control the expression of the recombinant gene. Data from this study suggest that the overexpression of the alpha-glucosidase was greatly decreased by sigma factor competition in the clpP mutant, due to the increased sigmas level in this mutant background.

Analysis of a 2,4,6-trichlorophenol-dehalogenating enrichment culture and isolation of the dehalogenating member Desulfitobacterium frappieri strain TCP-A.

An anaerobic, 2,4,6-trichlorophenol ortho-dehalogenating mixed culture was enriched from sediment of the river Saale (Germany). Two isolated dechlorinating colonies (MK1 and MK2) consisted of rods of different lengths and thicknesses, indicating heterogeneity. Following subcultivation with thiosulfate as alternative electron acceptor and cocultivation with Clostridium celerecrescensT, the 2,4,6-trichlorophenol-dehalogenating bacterium Desulfitobacterium frappieri strain TCP-A was isolated and characterized regarding its taxonomic properties and the spectrum of chlorophenols that it dehalogenated. Four other bacterial strains were coenriched and identified as organisms with closest phylogenetic relatedness to the Clostridium type strains C. indolis, C. glycolicum, C. hydroxybenzoicum and C. sporosphaeroides (16S rDNA sequence identities of 99.5, 99.2, 94.4, and 93.5%, respectively). Amplified ribosomal DNA restriction analysis of the original dehalogenating cultures MK1 and MK2 (when not exposed to thiosulfate) confirmed the microbial heterogeneity and revealed the presence of two additional species related to the type strains of C. celerecrescens and Clostridium propionicum. Only one copy of the 16S rRNA genes of Desulfitobacterium frappieri in each of the clone libraries of MK1 and MK2 (containing 136 and 56 clones, respectively) was found by dot-blot hybridization, suggesting a relatively low number of the dehalogenating bacterium within the enrichment culture.