title: Reduced production of the deleterious hydroxyl free radical during the final reperfusion of isolated rabbit heart with the use of an improved sodium lactobionate-based cardioplegic medium.
abstract: The production of free radicals during the reperfusion of hearts after prolonged ischemia might be responsible for the deleterious effects observed. Several strategies have attempted to limit this production or trap the radicals produced. This study aimed to evaluate the efficacy of a sodium lactobionate-based solution supplemented with 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl, a stable nitroxide free radical, in scavenging hydroxyl radicals produced during the reperfusion of the isolated rabbit heart. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl was administered just before the end of the storage period (6 hours) in a cardioplegic solution, either crystalloid solution or sodium lactobionate-based solution. The production of hydroxyl radicals was assessed through the production of dihydroxybenzoic acid, a reaction compound of hydroxyl radicals with salicylate. Two main isomers of dihydroxybenzoic acid were found in the coronary effluents: 2,3 and 2,5 dihydroxybenzoic acid. The production was 40-fold lower when the hearts received sodium lactobionate-based solution than when they received crystalloid solution (p < 0.001). The presence of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl had no influence on the production of hydroxyl radicals. The production of hydroxyl radicals was maximal during the first minute of the reperfusion. Iron ions, directly involved in the production of hydroxyl radicals, were shown to be complexed by sodium lactobionate in vitro. These results underlie the important role of lactobionate in the prevention of the reperfusion injury and the inefficacy of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl to decrease the production of hydroxyl radicals.
authors.affiliation: Department of Pharmacy-Toxicology, Centre Hospitalier Universitaire Henri Mondor, Créteil, France.
authors.forename: C
authors.initials: C
authors.lastname: Charloux
authors.forename: K
authors.initials: K
authors.lastname: Ishii
authors.forename: M
authors.initials: M
authors.lastname: Paul
authors.forename: D
authors.initials: D
authors.lastname: Loisance
authors.forename: A
authors.initials: A
authors.lastname: Astier
mesh_terms: D000225:Adenine; D000241:Adenosine / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D001639:Bicarbonates / Q000737:chemistry / Q000627:therapeutic use; D002314:Cardioplegic Solutions / Q000627:therapeutic use*; D002614:Chelating Agents / Q000737:chemistry / Q000627:therapeutic use; D015925:Cryopreservation; D003497:Cyclic N-Oxides / Q000627:therapeutic use; D004187:Disaccharides / Q000737:chemistry / Q000627:therapeutic use*; D005841:Gentisates; D006531:HEPES / Q000737:chemistry / Q000627:therapeutic use; D062385:Hydroxybenzoates / Q000037:antagonists & inhibitors / Q000737:chemistry; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors* / Q000737:chemistry; D058085:Iron Compounds / Q000737:chemistry; D007552:Isotonic Solutions / Q000627:therapeutic use; D008297:Male; D015425:Myocardial Reperfusion / Q000379:methods; D010710:Phosphates / Q000737:chemistry / Q000627:therapeutic use; D017680:Potassium Compounds / Q000627:therapeutic use; D011817:Rabbits; D000077325:Ringer's Lactate; D012980:Sodium Salicylate / Q000737:chemistry; D013113:Spin Labels; D014021:Tissue Preservation
chemical_list: D001639:Bicarbonates; D002314:Cardioplegic Solutions; D002614:Chelating Agents; D003497:Cyclic N-Oxides; D004187:Disaccharides; D005841:Gentisates; C082203:Henri-Mondor solution; D062385:Hydroxybenzoates; D058085:Iron Compounds; D007552:Isotonic Solutions; D010710:Phosphates; D017680:Potassium Compounds; D000077325:Ringer's Lactate; D013113:Spin Labels; C018369:potassium cardioplegic solution; D017665:Hydroxyl Radical; C005608:lactobionic acid; C009135:2,3-dihydroxybenzoic acid; D000225:Adenine; D000241:Adenosine; D006531:HEPES; C001803:tempol; C010925:2,5-dihydroxybenzoic acid; D012980:Sodium Salicylate