Results of catheter ablation of atrial fibrillation in hypertrophied hearts – Comparison between primary and secondary hypertrophy

AbstractBackground and purposeApproximately 20–25% of the patients with hypertrophic cardiomyopathy (HCM) develop atrial fibrillation (AF) during the clinical course of the disease, a percentage significantly larger than that of the general population. The purpose of the present study was to report on the procedural results of patients with AF and either primary or secondary left ventricular hypertrophy (LVH).Methods and subjectsTwenty-two consecutive HCM patients (55% male, mean age 57±8 years) with symptomatic AF, having undergone AF ablation procedures between September 2009 and July 2012 were compared with respect to procedural outcome and follow-up characteristics with 22 matched controls with secondary cardiac hypertrophy (64% male, 63±10 years) from our prospective AF catheter ablation registry.Results and conclusionRadiofrequency catheter ablation (RFCA) was successful in restoring long-term sinus rhythm in patients with LVH due to HCM and due to secondary etiology. However, patients with HCM needed more RFCA procedures and frequently additional antiarrhythmic drug therapy in order to maintain sinus rhythm

A prodrug form of a Plasmodium falciparum glutathione reductase inhibitor conjugated with a 4-anilinoquinoline

Glutathione (GSH), which is known to guard Plasmodium falciparum from oxidative damage, may have an additional protective role by promoting heme catabolism. An elevation of GSH content in parasites leads to increased resistance to chloroquine (CQ), while GSH depletion in resistant P. falciparum strains is expected to restore the sensitivity to CQ. High intracellular GSH levels depend inter alia on the efficient reduction of GSSG by glutathione reductase (GR). On the basis of this hypothesis, we have developed a new strategy for overcoming glutathione-dependent 4-aminoquinoline resistance. To direct both a 4-aminoquinoline and a GR inhibitor to the parasite, double-drugs were designed and synthesized. Quinoline-based alcohols (with known antimalarial activity) were combined with a GR inhibitor via a metabolically labile ester bond to give double-headed prodrugs. The biochemically most active double-drug 7 of this series was then evaluated as a growth inhibitor against six Plasmodium falciparum strains that differed in their degree of resistance to CQ; the ED50 values for CQ ranged from 14 to 183 nM. While the inhibitory activity of the original 4-aminoquinoline-based alcohol followed that of CQ in these tests, the double-drug exhibited similar efficiency against all strains, the ED50 being as low as 28 nM. For the ester 7, a dose-dependent decrease in glutathione content and GR activity and an increase in glutathione-S-transferase activity were determined in treated parasites. The drug was subsequently tested for its antimalarial action in vivo using murine malaria models infected with P. berghei. A 178% excess mean survival time was determined for the animals treated with 40 mg/kg 7 for 4 days. No cytotoxicity due to this compound was observed. Work is in progress to extend and validate the strategy outlined here.info:eu-repo/semantics/publishe