title: Atrial contractile dysfunction after short-term atrial fibrillation is reduced by verapamil but increased by BAY K8644.
abstract: BACKGROUND
  Reduced atrial contractility occurs after cessation of atrial fibrillation. Its mechanism is unknown, and no pharmacological treatment exists. It has been hypothesized that this atrial contractile dysfunction results from intracellular calcium overload due to rapid depolarizations during fibrillation. Accordingly, we examined the effects of drugs that reduce or increase transsarcolemmal calcium influx on postfibrillation atrial dysfunction. Furthermore, we examined whether the dysfunction could be attributed to atrial ischemia.
  
  
  RESULTS
  Atrial contractility after atrial fibrillation was examined in open-chest pigs paced with a constant ventricular rate after complete AV block. Atrial contractility was computed as systolic shortening of left atrial diameter divided by atrial preload. Three groups of six pigs each were subjected to two 5-minute periods of atrial fibrillation separated by 1 hour of AV pacing. Verapamil or the calcium channel agonist BAY K8644 was administered intravenously before the second fibrillation period. The degree and duration of postfibrillation atrial contractile dysfunction were reduced with verapamil but increased with BAY K8644. In a control group, parallel changes occurred after the first and second fibrillation periods. Atrial tissue content of creatine phosphate declined slightly during fibrillation, whereas the tissue content of ATP and lactate remained unchanged.
  
  
  CONCLUSIONS
  Atrial contractile dysfunction after short-term atrial fibrillation is reduced by the calcium antagonist verapamil, which suggests that transsarcolemmal calcium influx contributed to this dysfunction. The calcium agonist BAY K8644 increased postfibrillation atrial contractile dysfunction. Atrial ischemia was not observed during fibrillation.
authors.affiliation: Institute for Experimental Medical Research, University of Oslo, Ullevål Hospital, Norway. elizabeth.leistad@ioks.uio.no
authors.forename: E
authors.initials: E
authors.lastname: Leistad
authors.forename: G
authors.initials: G
authors.lastname: Aksnes
authors.forename: E
authors.initials: E
authors.lastname: Verburg
authors.forename: G
authors.initials: G
authors.lastname: Christensen
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001281:Atrial Fibrillation / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D005260:Female; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010725:Phosphocreatine / Q000378:metabolism; D013552:Swine; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D002120:Calcium Channel Agonists; D007773:Lactates; D010725:Phosphocreatine; D019344:Lactic Acid; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000255:Adenosine Triphosphate; D014700:Verapamil