title: Pharmacological postconditioning protects isolated rat hearts against ischemia-reperfusion injury: the role of mitochondrial permeability transition pore.
abstract: Postconditioning has been verified to provide cardioprotection and is associated with the state of mitochondrial permeability transition pore. However, there are a few limitations with clinical use of classic postconditioning; therefore, the purpose of this investigation was to study whether inhibition of mitochondrial permeability transition pore opening with cyclosporine A also provided cardioprotection. Langendorff-perfused Sprague-Dawley rat hearts were perfused for 20 minutes with Krebs-Henseleit buffer followed by 30 minutes of crystalloid cardioplegia and 60 minutes of reperfusion. Control hearts (Con group) were reperfused with Krebs-Henseleit buffer. Postconditioning hearts (Ipo group) were with six cycles of 10 seconds reocclusion separated by 10 seconds perfusion before reperfusion. Cyclosporine A postconditioning hearts (CsA group) were reperfused with Krebs-Henseleit buffer containing 0.8 μmol/L cyclosporine A at first 5 minutes of reperfusion. Compared with Con group, myocardial performance was better preserved in CsA group. Mitochondrial outer membrane integrity was preserved, with less cytosolic diffusion of cytochrome C (p < 0.05) and less frequency of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling-positive myocytes in Ipo and CsA group (p < 0.05). Postconditioning prevented apoptosis-related mitochondrial permeabilization and dysfunction after cardioplegic arrest. Cyclosporine A postconditioning had a better effect than classic postconditioning in myocardial performance.
authors.affiliation: Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Duan
authors.forename: Bingyang
authors.initials: B
authors.lastname: Ji
authors.forename: Kun
authors.initials: K
authors.lastname: Yu
authors.forename: Jinping
authors.initials: J
authors.lastname: Liu
authors.forename: Feilong
authors.initials: F
authors.lastname: Hei
authors.forename: Cun
authors.initials: C
authors.lastname: Long
mesh_terms: D000818:Animals; D017209:Apoptosis; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000037:antagonists & inhibitors; D016572:Cyclosporine / Q000008:administration & dosage; D045304:Cytochromes c / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006439:Hemodynamics; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D004791:Enzyme Inhibitors; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D016572:Cyclosporine; D045304:Cytochromes c; D021983:Cyclophilins