Mycobacteria exploit nitric oxide-induced transformation of macrophages into permissive giant cells.

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DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas.

Granulomas are immune cell aggregates formed in response to persistent inflammatory stimuli. Granuloma macrophage subsets are diverse and carry varying copy numbers of their genomic information. The molecular programs that control the differentiation of such macrophage populations in response to a chronic stimulus, though critical for disease outcome, have not been defined.

The new selective I(Ks)-blocking agent HMR 1556 restores sinus rhythm and prevents heart failure in pigs with persistent atrial fibrillation.

Background: Antiarrhythmic drugs for treatment of atrial fibrillation in patients with heart failure are limited by proarrhythmia and low efficacy. Experimental studies indicate that the pure I(Ks) blocking agents chromanol 293b and HMR 1556 prolong repolarization more markedly at fast than at slow heart rates and during beta-adrenergic stimulation. These properties may overcome some of the above quoted limitations.

Tridimensional activation patterns of acquired torsade-de-pointes tachycardias in dogs with chronic AV-block.

Background: Dogs with chronic AV block exposed to type-III antiarrhythmic agents develop polymorphic ventricular tachycardias (PVT). Controversy exists regarding PVT mechanism and underlying pathophysiology.

Methods And Results: In dogs with acute (n = 10, AAVB) or chronic AV block (n = 14, CAVB, 62 +/- 5 days after AV-node ablation) 60 pins (12 mm long, 4 bipolar electrodes) were inserted into both ventricles.

Biventricular hypertrophy in dogs with chronic AV block: effects of cyclosporin A on morphology and electrophysiology.

Chronic atrioventricular (AV) block (CAVB) and biventricular hypertrophy in dogs increase susceptibility to drug-induced polymorphic ventricular tachycardia (PVT). In various rodent models, cyclosporin A (CsA) prevented hypertrophy. A similar effect in the CAVB model would allow us to determine whether hypertrophy represents an epiphenomenon, the cause of electrophysiological changes, and/or the anatomic substrate for PVTs.

Pro- and antiarrhythmic effects of fast cardiac pacing in a canine model of acquired long QT syndrome.

Increasing the heart rate is one option for suppressing bradycardia-dependent polymorphic ventricular tachycardias (PVTs). The mechanisms underlying preventive pacing in acquired forms of the long QT syndrome (LQTs) are still not fully understood. Using two needle electrodes, local effective refractory periods (ERPs) were determined in the left (LV) and right ventricle (RV) in 20 dogs with acute AV node ablation before continuous pacing, during a 20-min period of continuous fast pacing (Cl 300 ms, fastpac) and during a 35-min recovery period with slow (Cl 500 ms) pacing.

Ventricular oversensing: a study of 101 patients implanted with dual chamber defibrillators and two different lead systems.

Unlabelled: Modern dual chamber ICD systems are able to overcome various sensing problems. However, improvement of their performance is still required. The aim of this study was to assess the sensing function in 101 consecutive patients (84 men, 17 women; mean age 63 +/- 12 years; mean follow-up 24 +/- 4 months) implanted with dual chamber defibrillators and integrated (IB) or dedicated bipolar (DB) lead systems.

Effects of acute ischemia, early extrabeats and propafenone on complex activation patterns in intact and ischemic canine hearts.

Although, sodium channel blockers have the ability to suppress nonsustained ventricular arrhythmias, an excessive drug-associated arrhythmic death rate has been reported in patients with coronary heart disease (CHD). Sodium channel blockers should prevent initiation of reentry activation by reducing directional differences in cardiac conduction (anisotropy). However, in vitro data demonstrated, that reduction of membrane excitability, e.

Refractory patterns and susceptibility to drug-induced polymorphic ventricular tachycardias in dogs with chronic atrioventricular block: relation to the type of anesthesia.

Controversy exists as to the homogeneity of repolarization throughout the canine ventricular wall in vivo. The type of anesthesia has been shown to affect regional differences in monophasic action potential duration and the inducibility of polymorphic ventricular tachycardias (PVTs) in normal canine hearts. This study was conducted to determine refractory patterns and arrhythmia susceptibility in relation to halothane or pentobarbital anesthesia in dogs with chronic atrioventricular block and biventricular hypertrophy.

[Atrial fibrillation: pathophysiology].

Background: Although several classical studies seemed to provide clear ideas on the pathophysiology of atrial fibrillation, current concepts have to be modified on the basis of more recent findings.

Reentrant Circuits: Based on the findings of Garrey and of Moe & Abildskov, atrial fibrillation has long been considered as the prototype of an arrhythmia being caused by multiple, random reentrant circuits, the number of which would determine the stability of the reentrant process. Local refractory and conduction properties would determine the size of individual circuits, a hypothesis quite convincing with respect to refractoriness, but so far hard to prove with respect to conduction.

Suppression of atrial fibrillation by multisite and septal pacing in a novel experimental model.

Objectives: To evaluate the preventive efficacy of multisite and septal atrial pacing in an experimental model.

Methods: Sterile right atrial pericarditis was induced in 12 foxhounds to provide an anatomical substrate for atrial fibrillation (AF). As a trigger mechanism, atrial extrasystoles were simulated by constant asynchronous pacing at a cycle length of 1000 ms from randomly selected right or left atrial electrodes, using a biatrial epicardial multielectrode with 128 bipoles.

Variability of Holter electrocardiographic findings in patients fulfilling the noninvasive MADIT criteria. Multicenter Automatic Defibrillator Implantation Trial.

In the MADIT study, a selected group of postinfarction patients with asymptomatic nonsustained ventricular tachycardia (NSVT) has been shown to benefit from prophylactic ICD treatment. The present study analyzed the variability of NSVT in a patient population fulfilling the non-invasive MADIT criteria. Three consecutive Holter ECGs were performed in weekly intervals in 68 postinfarction patients with an LVEF < or = 0.

Effects of the I(Kr)-blocking agent dofetilide and of the I(Ks)-blocking agent chromanol 293b on regional disparity of left ventricular repolarization in the intact canine heart.

Recent in vitro studies have described regional differences of ion current expression and function, possibly accounting for reduced homogeneity of repolarization in the heart. In 11 intact canine hearts regional disparity of repolarization was determined at baseline and after administration of the I(Kr) blocking agent dofetilide (30 microg/kg) and the I(Ks)-blocking agent chromanol 293b (10 mg/kg). Effective refractory periods (ERPs) were determined through up to 10 needle electrodes inserted into basal, midwall and apical regions of the left ventricular wall using the extrastimulus technique (cycle length [CL] 300 and 850 ms).