title: Inhibition of Na,K-ATPase by external electrical cardioversion in a sheep model of atrial fibrillation.
abstract: BACKGROUND
  Electrical external cardioversion commonly used to treat atrial fibrillation (AF) is associated with myocardial membrane damage and disturbances in ionic homeostasis (hemodynamically unstable). The present study was designed to investigate whether alterations in ionic homeostasis observed were due in part to changes in the myocardial activity of Na,K-ATPase.
  
  
  RESULTS
  AF was induced by pacing in ten anesthetized sheep divided into two groups. Group I (n = 4) received a single external countershock of 360 J after three episodes of AF lasting 10 minutes. Group II (n = 6) served as controls. Activity, responsiveness to ouabain, and membrane expression of catalytic alpha and beta subunits of Na,K-ATPase in sarcolemmal myocardial membrane fractions were investigated. Membrane fluidity and fatty acid composition, and plasma levels of atrial natriuretic factor (ANF) also were measured. One shock after episodes of AF significantly decreased ventricular Na,K-ATPase activity up to 50% (P < 0.001) without modification of atrial activity at the membrane level. Sites with low affinity to ouabain showed a fivefold lower affinity for ouabain in the cardioversion group than in the control group (IC50 = 7.9 micromol/L vs 40 micromol/L ouabain, P < 0.05). Plasma levels of ANF were significantly increased in the cardioversion group compared with the control group. These changes were independent of membrane modulation in terms of expression of Na,K-ATPase, membrane fluidity, and fatty acid composition.
  
  
  CONCLUSIONS
  This study suggests that left ventricular perturbation of ionic homeostasis subsequent to transthoracic cardioversion could result from inactivation of Na,K-ATPase activity.
authors.affiliation: Laboratoire de Recherche Cardiologique, University of Marseille, School of Medicine, Centre Hospitalo-Universitaire Nord, France. Hematim@pharmacie.univ-mrs.fr
authors.forename: J M
authors.initials: JM
authors.lastname: Maixent
authors.forename: O
authors.initials: O
authors.lastname: Barbey
authors.forename: S
authors.initials: S
authors.lastname: Pierre
authors.forename: M J
authors.initials: MJ
authors.lastname: Duran
authors.forename: S
authors.initials: S
authors.lastname: Sennoune
authors.forename: M
authors.initials: M
authors.lastname: Bourdeaux
authors.forename: P
authors.initials: P
authors.lastname: Ricard
authors.forename: S
authors.initials: S
authors.lastname: Lévy
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers; D015153:Blotting, Western; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects; D004195:Disease Models, Animal; D004554:Electric Countershock / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors; D005227:Fatty Acids / Q000378:metabolism; D017136:Ion Transport / Q000502:physiology; D008560:Membrane Fluidity; D008861:Microsomes / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology*; D010042:Ouabain; D012508:Sarcolemma / Q000201:enzymology; D012756:Sheep; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D010042:Ouabain; D009320:Atrial Natriuretic Factor; D000254:Sodium-Potassium-Exchanging ATPase