title: Preconditioning with cromakalim improves long-term myocardial preservation for heart transplantation.
abstract: BACKGROUND
  Myocardial preservation for heart transplantation relies on hyperkalemic cardiac arrest and hypothermic storage. Our study investigated whether pretreatment with a potassium-channel opener (cromakalim) before prolonged storage in an extracellular fluid improves left ventricular recovery.
  
  
  METHODS
  Rabbit hearts were submitted to 6-hours' cold storage and assessed on a blood-perfused isolated heart preparation. Hemodynamic recovery, enzyme release (creatine kinase and lactate dehydrogenase), and adenine nucleotide content were determined. Five groups were tested: control (n=6), no ischemia; UW group (n=7), hearts arrested with and stored in University of Wisconsin solution; STH group (n=5), hearts arrested with and stored in St. Thomas' Hospital solution; cromakalim group (n=6), hearts pretreated with cromakalim (30 microg/kg) before arrest with and storage in St. Thomas' Hospital solution; and glibenclamide group (n=5), hearts pretreated with cromakalim followed by glibenclamide (a potassium-channel blocker) before arrest with and storage in St. Thomas' Hospital solution.
  
  
  RESULTS
  Hemodynamic recovery was improved and enzyme release was lower in the UW group than in the STH group. Compared with the STH group, the group pretreated with cromakalim had significantly decreased left ventricular end-diastolic pressures, increased left ventricular developed pressures, increased maximal values of positive and negative rates of rise of left ventricular pressure, and increased time constant of isovolumetric relaxation. Hemodynamic recovery was similar in the UW group and cromakalim groups. Glibenclamide did not abolish the effects of cromakalim. None of the protocols affected myocardial energy stores.
  
  
  CONCLUSIONS
  Pretreatment with cromakalim affords additional protection to that provided by cardioplegic arrest and prolonged cold storage using an extracellular solution. The intracellular mechanisms involved remain to be determined.
authors.affiliation: Centre de Recherches Chirurgicales Henri Mondor, and Pharmacie Centrale, Hôpital Henri Mondor, Créteil, France.
authors.forename: M
authors.initials: M
authors.lastname: Kirsch
authors.forename: C
authors.initials: C
authors.lastname: Baufreton
authors.forename: C
authors.initials: C
authors.lastname: Fernandez
authors.forename: S
authors.initials: S
authors.lastname: Brunet
authors.forename: F
authors.initials: F
authors.lastname: Pasteau
authors.forename: A
authors.initials: A
authors.lastname: Astier
authors.forename: D Y
authors.initials: DY
authors.lastname: Loisance
mesh_terms: D000227:Adenine Nucleotides / Q000032:analysis; D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D002314:Cardioplegic Solutions / Q000494:pharmacology; D003326:Coronary Circulation; D003404:Creatinine / Q000378:metabolism; D019806:Cromakalim / Q000494:pharmacology*; D005978:Glutathione; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D016027:Heart Transplantation; D006439:Hemodynamics; D007328:Insulin; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D015221:Potassium Channels / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D011887:Raffinose; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D000227:Adenine Nucleotides; D001639:Bicarbonates; D002314:Cardioplegic Solutions; D007328:Insulin; D019188:Organ Preservation Solutions; D015221:Potassium Channels; C041711:St. Thomas' Hospital cardioplegic solution; C055206:University of Wisconsin-lactobionate solution; D019806:Cromakalim; D012965:Sodium Chloride; D000493:Allopurinol; D011189:Potassium Chloride; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D008274:Magnesium; D000241:Adenosine; D002122:Calcium Chloride; D011887:Raffinose; D005905:Glyburide