Torsade de pointes induced by intravenous amiodarone therapy accompanied by marked augmentation of the transmural dispersion of repolarization in a patient with tachycardia-induced-cardiomyopathy.

We report a 77-year-old human on renal dialysis for end-stage renal disease with heart failure and atrial fibrillation (AF) complicated by a high ventricular frequency. The underlying disease was thought as tachycardia-induced-cardiomyopathy. Intravenous infusion of amiodarone was initiated, and direct current cardioversion succeeded in converting AF to sinus rhythm. Then, excessive increases in the QT and Tpeak-Tend (Tp-e) intervals were seen and hypokalemia induced by hemodialysis led to the development of numerous episodes of torsades de pointes (TdP). Magnesium repletion was effective in preventing TdP, while Tp-e intervals returned to the previous values 2 days after the discontinuation of amiodarone.

Impact of first documented rhythm on cost-effectiveness of extracorporeal cardiopulmonary resuscitation.

OBJECTIVES: Recommendations for extracorporeal cardiopulmonary resuscitation (ECPR) state that appropriate patient selection is important for the sake of efficacy and cost-effectiveness of ECPR. It is not known whether first documented rhythm plays a prominent role in economic outcomes of patients with cardiac arrest who received ECPR. METHODS AND RESULTS: We reviewed the medical records of 120 consecutive patients who received extracorporeal membrane oxygenation (ECMO) assisted CPR due to refractory circulatory collapse between 2008 and 2016 in Urasoe General Hospital. The patients presented with ventricular fibrillation or pulseless ventricular tachycardia (VF/VT; n = 59, 49.2%) or with asystole or pulseless electric activity (ASY/PEA; n = 61, 50.8%) as the first documented rhythm. Multivariate logistic regression analysis identified shorter duration from collapse to ECMO initiation (odds ratio, 1.95 per 10 min; 95% confidence interval, 1.32-2.89, p = 0.001), bystander CPR (odds ratio, 5.53; 95% confidence interval, 1.36-22.5, p = 0.017), and first documented rhythm of VF/VT (odds ratio, 3.93; 95% confidence interval, 1.30-11.8, p = 0.015) as clinical predictors for neurologically intact survival. Total hospital cost per life saved by ECPR for ASY/PEA was approximately twice that for VF/VT ($213,656 vs. $101,669). ECPR yielded Quality adjusted life years (QALYs) of 3.32 at a mean total cost of $39,634 for VF/VT and QALYs of 1.17 at a mean cost of $35,609 for ASY/PEA. The cost per QALYs was $11,081 for VF/VT and $29,447 for ASY/PEA. The incremental cost-effectiveness ratio of ECPR vs. conventional CPR was estimated to be $ 16,246 per QALY gained. CONCLUSION: ECPR for patients presenting with VF/VT was found to be highly cost-effective and ECPR for patients presenting with ASY/PEA was borderline cost-effective.

Development of photoaffinity derivatives of the antitumor macrolide aplyronine A, a PPI-inducer between actin and tubulin.

The antitumor and actin-depolymerizing marine macrolide aplyronine A (ApA) synergistically binds to tubulin in association with actin, and prevents spindle formation and mitosis. While the crystal structure of the actin ApA complex was solved in 2006, its interaction with the tubulin heterodimer has not been clarified. To investigate the binding modes of ApA as a unique protein-protein interaction (PPI)-inducer between these two cytoskeletal proteins, we prepared its photoaffinity acetylene and fluorescent derivatives with the aid of molecular modeling studies for probe design. Among these three derivatives, the ApA-PPA-TAMRA probe specifically photoreacted with both actin and tubulin in vitro. However, the photolabeling yield of tubulin was quite low (up to ∼1%), and one of the major side-reactions was the addition of a water molecule to the carbene species generated from an aryldiazirine moiety on the hydrophilic surface of actin.