Preconditioning with cromakalim improves long-term myocardial preservation for heart transplantation.
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.
Kirsch
M
M
Centre de Recherches Chirurgicales Henri Mondor, and Pharmacie Centrale, Hôpital Henri Mondor, Créteil, France.
Baufreton
C
C
Fernandez
C
C
Brunet
S
S
Pasteau
F
F
Astier
A
A
Loisance
D Y
DY
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
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