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Fatal Arrhythmia (fatal + arrhythmia)
Selected AbstractsCollation, assessment and analysis of literature in vitro data on hERG receptor blocking potency for subsequent modeling of drugs' cardiotoxic propertiesJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2009Sebastian Polak Abstract The assessment of the torsadogenic potency of a new chemical entity is a crucial issue during lead optimization and the drug development process. It is required by the regulatory agencies during the registration process. In recent years, there has been a considerable interest in developing in silico models, which allow prediction of drug,hERG channel interaction at the early stage of a drug development process. The main mechanism underlying an acquired QT syndrome and a potentially fatal arrhythmia called torsades de pointes is the inhibition of potassium channel encoded by hERG (the human ether-a-go-go-related gene). The concentration producing half-maximal block of the hERG potassium current (IC50) is a surrogate marker for proarrhythmic properties of compounds and is considered a test for cardiac safety of drugs or drug candidates. The IC50 values, obtained from data collected during electrophysiological studies, are highly dependent on experimental conditions (i.e. model, temperature, voltage protocol). For the in silico models' quality and performance, the data quality and consistency is a crucial issue. Therefore the main objective of our work was to collect and assess the hERG IC50 data available in accessible scientific literature to provide a high-quality data set for further studies. Copyright © 2008 John Wiley & Sons, Ltd. [source] Fatal Inappropriate ICD ShockJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2007CHRISTIAN VELTMANN M.D. Introduction: Inappropriate implantable cardioverter defibrillator (ICD) therapy carries a low but relevant risk of ventricular proarrhythmia. In the present case, the extremely rare event of a fatal arrhythmia caused by inappropriate therapy is reported. Dislodgement of the ventricular lead to the level of the tricuspid annulus led to additional sensing of the atrial signal during sinus tachycardia. Spuriously, ventricular fibrillation was sensed and induced inappropriate ICD shocks. The fourth inappropriate shock caused ventricular fibrillation, which was subsequently undersensed by the dislodged lead due to low ventricular amplitudes. The ICD started antibradycardic pacing during ventricular fibrillation. After initial successful resuscitation, the patient died 1 week later due to severe hypoxic brain damage. Although not preventable in the present case, it underlines the necessity of immediate interrogation of the ICD after ICD therapy and deactivation of the ICD in the setting of a dislodged endocardial lead and intensive care monitoring of the patient until revision. [source] Effects of Sildenafil Citrate on Defibrillation EfficacyJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2006KREKWIT SHINLAPAWITTAYATORN M.D. Introduction: Although fatal arrhythmia and sudden death have been reported in patients taking sildenafil citrate, its effect on defibrillation efficacy has not been investigated. The aim of this study was to test the hypothesis that sildenafil citrate increases the shock strength required to successfully defibrillate during ventricular fibrillation (VF). Methods and Results: A total of 26 pigs (20,25 kg) were randomly assigned into three groups. In each group, the defibrillation threshold (DFT) was determined at the beginning of the study using a three-reversal up/down protocol. Each shock (RV-SVC, biphasic) was delivered after 10 seconds of VF. Group 1 (n = 10) received 50 mg and group 2 (n = 10) received 100 mg of sildenafil citrate intravenously at a rate of 2 mL/minute for 50 minutes. Group 3 (n = 6) received 100 mL of saline intravenously at the same rate as in group 1. The DFT was determined again after the drug (drug-DFT) and saline (saline-DFT) administration. For 100-mg sildenafil citrate infusion, the DFT (483 ± 39 V, 18 ± 3 J) was significantly (P < 0.003 and P < 0.01, respectively) higher than the control-DFT (407 ± 123 V, 13 ± 7 J). This sildenafil citrate infusion increased the DFT ,19% by voltage, and ,38% by total energy. After 50-mg sildenafil citrate infusion, the DFT (454 ± 28 V, 15 ± 2 J) was not different than the control DFT (449 ± 28 V, 15 ± 2 J). Saline infusion (391 ± 18 V, 12 ± 1 J) did not alter the control DFT (399 ± 22 V, 12 ± 1 J). Conclusion: The 100-mg sildenafil citrate infusion, representing a supra-therapeutic plasma level, significantly increased the DFT. This finding indicates that VF occurring during supra-therapeutic sildenafil citrate treatment would require a stronger shock to successfully defibrillate. [source] Five-Year Follow-Up of Valve Replacement with the Jyros Bileaflet Mechanical ValveARTIFICIAL ORGANS, Issue 1 2000Koji Onoda Abstract: Jyros bileaflet rotating valves were implanted as a clinical trial conducted in Japan, and the 5-year results were assessed. Nineteen patients underwent implantation of the valves: 14 in the mitral and 5 in the aortic position. The mean follow-up period was 65.4 ± 15.7 months. There was 1 case of late death due to fatal arrhythmia and another case of cerebral thromboembolism (1.0% per patient year). All survivors were in New York Heart Association class I. On the early postoperative cinefluorography, 8 valves (42.1%) showed rotation of the leaflets. However, in the latest assessment 6 valves (33.3%) showed rotation, some valves had stopped rotation, and others had started to rotate during the follow-up period. The Jyros valve functions effectively, similar to other bileaflet valves. However, because the correlation between thromboembolism and the rotation mechanism is not clear, further follow-up of our patients and more implant studies are necessary to elucidate this issue. [source] | ||||||||||