eplerenone and Tachycardia

Over the past years, the importance of the renin-angiotensin-aldosterone system in atrial fibrillation (AF) pathophysiology has been recognised. Lately, the role of aldosterone in AF pathophysiology and mineralocorticoid receptor (MR) antagonism in "upstream" AF treatment is discussed. Hypothesising that selective MR antagonism might also influence atrial ion currents (L-type calcium current [I (Ca,L)], transient outward potassium current [I (to)], sustained outward potassium current [I (sus)]) and their tachycardia-induced remodelling, the effects of an eplerenone treatment were studied in a rabbit model. Six groups each with four animals were built. Animals of the control group received atrial pacing leads, but in contrast to the pacing groups, no atrial tachypacing (600 per minute for 24 and 120 h immediately before heart removal) was applied. Animals of the eplerenone groups were instrumented/paced as the corresponding control/pacing groups, but were additionally treated with eplerenone (7 days before heart removal). Atrial tachypacing was associated with a reduction of I (Ca,L). I (to) was decreased after 24 h of tachypacing, but returned to control values after 120 h. In the absence of rapid atrial pacing, MR antagonism reduced I (Ca,L) to a similar extent as 120 h of tachypacing alone. Based on this lower "take-off level", I (Ca,L) was not further decreased by high-rate pacing. I (to) and its expected tachycardia-induced alterations were not influenced by MR antagonism. In our experiments, selective MR antagonism influenced atrial I (Ca,L) and its tachycardia-induced alterations. As changes of I (Ca,L) are closely linked with atrial calcium signalling, the relevance of these alterations in AF pathophysiology and, accordingly, AF treatment is likely and has to be further evaluated.

Topics: Animals; Atrial Fibrillation; Calcium Channels, L-Type; Cardiac Pacing, Artificial; Disease Models, Animal; Electric Conductivity; Eplerenone; Female; Heart Atria; Heart Conduction System; Ion Channel Gating; Mineralocorticoid Receptor Antagonists; Potassium Channels; Rabbits; Spironolactone; Tachycardia

High-rate short-duration ventricular pacing induces myocardial hypokinesis that persists once the hemodynamic conditions have been recovered. The aim was to study the factors that determine the persistence of myocardial dysfunction when ventricular tachycardia has ceased and hemodynamic conditions have been restored.. An in vivo experimental pig model was used consisting of a ventricular pacing series (n=10), a ventricular pacing and aldosterone blockade (eplerenon) series (n=6), and a control series without ventricular pacing (n=6). Electrical stimulation was performed from the epicardial base of the left ventricle at a frequency 60% above the basal rate for 2 hours followed by a recovery period of 60 minutes. Cardiac and myocardial function parameters were studied. Plasma levels of aldosterone, renin activity, and glutathione were measured.. Electrically induced tachycardia produced hemodynamic and myocardial changes that persisted after stimulation had ceased, accompanied by an increase in aldosterone and a coronary flow decrease. These changes were not seen when aldosterone activity was blocked by eplerenon. There was a non-significant elevation in glutathione levels.. These data show that although participation of other neurohormones cannot be ruled out, aldosterone blockade (eplerenon) ameliorates myocardial dysfunction persisting after ventricular tachycardia by preventing coronary endothelial dysfunction.

Topics: Animals; Cardiomyopathies; Eplerenone; Female; Male; Mineralocorticoid Receptor Antagonists; Spironolactone; Swine; Tachycardia

Renin-angiotensin-aldosterone system activation may be involved in the pathogenesis of atrial arrhythmias in congestive heart failure (CHF). The effects of aldosterone blockade on atrial tachyarrhythmias have not been evaluated. This study's aim was to determine whether selective aldosterone blockade suppresses atrial tachyarrhythmia inducibility and modifies atrial electrical and/or structural remodeling in a canine model of rapid ventricular pacing (RVP)-induced CHF.. Dogs were assigned randomly to treatment with oral placebo or eplerenone (50 mg/day) and divided into four groups: two sham-operated (no RVP) and two RVP groups. After 5 weeks of no RVP or RVP at 230 beats/min along with concurrent placebo or eplerenone treatment, dogs underwent electrophysiologic and echocardiographic studies. Sustained atrial tachyarrhythmia inducibility (>10-minute duration), atrial effective refractory periods (ERPs), systolic and diastolic function, and left atrial and left ventricular (LV) chamber sizes were assessed. Placebo-treated RVP dogs developed CHF with LV systolic and diastolic dysfunction, left atrial and LV enlargement, increased atrial ERPs, and inducible sustained atrial tachyarrhythmias. Eplerenone treatment in RVP dogs significantly suppressed sustained atrial tachyarrhythmia inducibility, nonuniformly prolonged atrial ERPs and attenuated LV diastolic dysfunction without modifying left atrial or LV dilation or ejection fractions in CHF. Isoproterenol (2-4 microg/min) reversed eplerenone's atrial antiarrhythmic and ERP prolonging effects in CHF. Eplerenone did not alter atrial ERPs in sham (no RVP) dogs without CHF.. Eplerenone suppresses inducibility of sustained atrial tachyarrhythmias, selectively prolongs atrial ERPs, and attenuates LV diastolic remodeling in RVP-induced CHF. Aldosterone blockade may be a promising new approach for atrial tachyarrhythmia prevention in CHF.

Topics: Administration, Oral; Animals; Dogs; Eplerenone; Heart Atria; Heart Conduction System; Heart Failure; Mineralocorticoid Receptor Antagonists; Random Allocation; Spironolactone; Tachycardia; Treatment Outcome; Ventricular Dysfunction, Left

Topics: Administration, Oral; Animals; Dogs; Eplerenone; Heart Atria; Heart Conduction System; Heart Failure; Mineralocorticoid Receptor Antagonists; Random Allocation; Spironolactone; Tachycardia; Treatment Outcome; Ventricular Dysfunction, Left