title: Acute infusion of levosimendan enhances atrial fibrillation in an experimental whole-heart model.
abstract: BACKGROUND
  The calcium sensitizer levosimendan is clinically employed in decompensated heart failure. The aim of the present study was to assess effects of levosimendan on atrial electrophysiology in an experimental whole-heart model.
  
  
  RESULTS
  13 rabbit hearts were isolated and Langendorff-perfused. Thereafter, hearts were paced at cycle lengths of 350ms, 250ms and 200ms in the atrium. A standardized protocol employing atrial burst pacing induced atrial fibrillation (AF) in 4 of 13 hearts under baseline conditions (mean: 3.3±2.1 episodes). Subsequently, levosimendan was administered in two concentrations (0.25μM, 0.5μM). Two monophasic action potential recordings on the left- and two on the right atrial epicardium displayed a decrease of atrial action potential duration (aAPD, -27ms, p<0.05) and atrial effective refractory period (aERP; -29ms, p<0.05) under the influence of 0.5μM levosimendan. The described alterations of atrial electrophysiology led to and increased inducibility of AF. Of note, treatment with 0.25μM levosimendan resulted in induction of AF in 11 of 13 hearts (mean: 8.9±3.5 episodes). Under the influence of 0.5μM levosimendan 12 of 13 hearts were inducible (mean: 9.8±3.8 episodes).
  
  
  CONCLUSIONS
  In the present study acute infusion of levosimendan in isolated rabbit hearts resulted in an abbreviation of atrial action potential duration and a reduction of aERP. This led to a significantly elevated inducibility of atrial fibrillation. These results suggest a proarrhythmic effect of levosimendan regarding atrial fibrillation. This aspect should be further investigated in the clinical setting.
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany. Electronic address: gerrit.frommeyer@ukmuenster.de.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Frommeyer
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Kohnke
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Ellermann
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Dirk G
authors.initials: DG
authors.lastname: Dechering
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Kochhäuser
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Reinke
authors.affiliation: Clinic of Exotic Pets, Reptiles, Exotic and Feral Birds, University of Hanover, Hanover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Fehr
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Eckardt
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001281:Atrial Fibrillation / Q000139:chemically induced* / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006835:Hydrazones / Q000008:administration & dosage* / Q000009:adverse effects*; D009924:Organ Culture Techniques; D011724:Pyridazines / Q000008:administration & dosage* / Q000009:adverse effects*; D011817:Rabbits; D000077464:Simendan; D013997:Time Factors
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan
keywords: Atrial fibrillation; Atrial refractory period; Levosimendan; Therapeutic safety