title: Adenosine triphosphate-dependent potassium channel modulation and cardioplegia-induced protection of human atrial muscle in an in vitro model of myocardial stunning.
abstract: OBJECTIVE
  Although adenosine triphosphate-dependent potassium channel openers have been shown to enhance cardioplegic protection in animal myocardium, there is a lack of data on human cardiac tissues. We aimed at determining, on human atrial muscle, whether adenosine triphosphate- dependent potassium channels are involved in protection caused by high-potassium cardioplegia and whether adenosine triphosphate-dependent potassium channel activation might improve cardioplegic protection in an in vitro model of myocardial stunning.
  
  
  METHODS
  Human atrial trabeculae were obtained from adult patients undergoing cardiac operations. In an organ bath at 37 degrees C, the preparations were subjected to 60 minutes of hypoxia at a high stimulation rate either in Tyrode solution (control, n = 17) or in St Thomas' Hospital solution without additives (n = 6) or associated with 100 nmol/L bimakalim (n = 7) or 1 micromol/L glibenclamide (n = 7), followed by 60 minutes of reoxygenation and 15 minutes of positive inotropic stimulation with 1 micromol/L dobutamine.
  
  
  RESULTS
  Atrial developed tension was reduced by hypoxia to 27% +/- 5% of baseline and incompletely recovered after reoxygenation to 38% +/- 7%, whereas dobutamine restored contractility to 74% +/- 7% of basal values. St Thomas' Hospital solution with or without bimakalim improved developed tension after reoxygenation and dobutamine (P <.0001 vs control), whereas glibenclamide inhibited these protective effects of cardioplegic arrest (P =.001 vs St Thomas' Hospital solution). After reoxygenation, the protective effect of bimakalim disappeared at a high pacing rate (400- and 300-ms cycle length) but recovered during dobutamine superfusion.
  
  
  CONCLUSIONS
  Adenosine triphosphate-dependent potassium channels are likely involved in the cardioprotective effects of cardioplegia in human atrial trabeculae and adenosine triphosphate-dependent potassium channel activation with bimakalim used as an additive to cardioplegia enhanced protection.
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Department of Cardiac Surgery and Second Section of Cardiology, University of Rome "La Sapienza," Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Monti
authors.forename: K
authors.initials: K
authors.lastname: Iwashiro
authors.forename: S
authors.initials: S
authors.lastname: Picard
authors.forename: A
authors.initials: A
authors.lastname: Criniti
authors.forename: S
authors.initials: S
authors.lastname: La Francesca
authors.forename: G
authors.initials: G
authors.lastname: Ruvolo
authors.forename: U
authors.initials: U
authors.lastname: Papalia
authors.forename: P P
authors.initials: PP
authors.lastname: Campa
authors.forename: B
authors.initials: B
authors.lastname: Marino
authors.forename: P E
authors.initials: PE
authors.lastname: Puddu
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D000328:Adult; D000368:Aged; D016280:Atrial Function, Right / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology; D001639:Bicarbonates; D002122:Calcium Chloride; D002314:Cardioplegic Solutions; D002316:Cardiotonic Agents / Q000494:pharmacology; D015687:Cell Hypoxia; D004095:Dihydropyridines / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006324:Heart Arrest, Induced; D006801:Humans; D066298:In Vitro Techniques; D008274:Magnesium; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D017682:Myocardial Stunning / Q000503:physiopathology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011189:Potassium Chloride; D012965:Sodium Chloride
chemical_list: D001578:Benzopyrans; D001639:Bicarbonates; D002314:Cardioplegic Solutions; D002316:Cardiotonic Agents; D004095:Dihydropyridines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C041711:St. Thomas' Hospital cardioplegic solution; D004280:Dobutamine; D012965:Sodium Chloride; C061050:bimakalim; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D008274:Magnesium; D002122:Calcium Chloride; D005905:Glyburide