title: Proarrhythmic effects of aldosterone during myocardial ischemia-reperfusion: implication of the sarcolemmal-KATP channels.
abstract: OBJECTIVE
  To assess the electrophysiological impact of aldosterone during myocardial ischemia-reperfusion.
  
  
  METHODS
  We used an in vitro model of "border zone" using rabbit right ventricle and standard microelectrodes.
  
  
  RESULTS
  Aldosterone (10 and 100 nmol/L) shortened ischemic action potential [action potential duration at 90% of repolarization (APD90), from 55 ± 3 to 39 ± 1 ms and 36 ± 3 ms, respectively, P < 0.05] and induced resting membrane potential (RMP) hyperpolarization in the nonischemic zone (from -83 ± 1 to -93 ± 7 mV and -94 ± 3 mV, respectively, P < 0.05) and in the ischemic zone during reperfusion (from -81 ± 2 to -88 ± 2 mV and -91 ± 2 mV, respectively, P < 0.05). Bimakalim, an ATP-sensitive potassium (K(ATP)) channel opener, also induced RMP hyperpolarization and APD90 shortening. Aldosterone (10 and 100 nmol/L) increased APD90 dispersion between ischemic and nonischemic zones (from 96 ± 3 to 117 ± 5 ms and 131 ± 6 ms, respectively, P < 0.05) and reperfusion-induced severe premature ventricular contraction occurrence (from 18% to 67% and 75%, respectively, P < 0.05). Adding glibenclamide, a nonspecific K(ATP) antagonist, to aldosterone superfusion abolished these effects different to sodium 5-hydroxydecanoate, a mitochondrial-K(ATP) antagonist.
  
  
  CONCLUSIONS
  In this in vitro rabbit model of border zone, aldosterone induced RMP hyperpolarization and decreased ischemic APD90 evoking the modulation of K currents. Glibenclamide prevented these effects different to 5-hydroxydecanoate, suggesting that sarcolemmal-K(ATP) channels may be involved in this context.
authors.affiliation: *Department of Cardiology, CHU de Caen, Caen, France; †Research Unit Signalisation, Électrophysiologie et Imagerie des Lésions d'Ischémie-Reperfusion Myocardique, Université de Caen Basse-Normandie, Caen, France; ‡Department of Cardiovascular Sciences, Sapienza University, Rome, Italy; and §Université de Caen Basse-Normandie, Medical School, Caen, France.
authors.forename: Joachim
authors.initials: J
authors.lastname: Alexandre
authors.forename: Paolo-Emilio
authors.initials: PE
authors.lastname: Puddu
authors.forename: Christophe
authors.initials: C
authors.lastname: Simard
authors.forename: Thomas
authors.initials: T
authors.lastname: Hof
authors.forename: Laurent
authors.initials: L
authors.lastname: Sallé
authors.forename: Romain
authors.initials: R
authors.lastname: Guinamard
authors.forename: Alain
authors.initials: A
authors.lastname: Manrique
authors.forename: René
authors.initials: R
authors.lastname: Rouet
authors.forename: Farzin
authors.initials: F
authors.lastname: Beygui
authors.forename: Paul
authors.initials: P
authors.lastname: Milliez
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000450:Aldosterone / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D054086:KATP Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D010477:Perfusion; D011817:Rabbits; D012508:Sarcolemma / Q000378:metabolism*
chemical_list: D001578:Benzopyrans; D004095:Dihydropyridines; D054086:KATP Channels; D000450:Aldosterone; C061050:bimakalim; D005905:Glyburide