title: Cyclosporine A at reperfusion fails to reduce infarct size in the in vivo rat heart.
abstract: We examined the effects on infarct size and mitochondrial function of ischemic (Isch), cyclosporine A (CsA) and isoflurane (Iso) preconditioning and postconditioning in the in vivo rat model. Anesthetized open-chest rats underwent 30 min of ischemia followed by either 120 min (protocol 1: infarct size assessment) or 15 min of reperfusion (protocol 2: assessment of mitochondrial function). All treatments administered before the 30-min ischemia (Pre-Isch, Pre-CsA, Pre-Iso) significantly reduced infarct as compared to control. In contrast, only Post-Iso significantly reduced infarct size, while Post-Isch and Post-CsA had no significant protective effect. As for the postconditioning-like interventions, the mitochondrial calcium retention capacity significantly increased only in the Post-Iso group (+58 % vs control) after succinate activation. Only Post-Iso increased state 3 (+177 and +62 %, for G/M and succinate, respectively) when compared to control. Also, Post-Iso reduced the hydrogen peroxide (H2O2) production (-46 % vs control) after complex I activation. This study suggests that isoflurane, but not cyclosporine A, can prevent lethal reperfusion injury in this in vivo rat model. This might be related to the need for a combined effect on cyclophilin D and complex I during the first minutes of reperfusion.
authors: Inserm U1060, CarMeN Laboratoire, Laboratoire de Physiologie Lyon Nord, Lyon University, Univ Lyon-1, 8 Av Rockefeller, 69373, Lyon, France.
authors: Damien
authors: D
authors: De Paulis
authors: Pascal
authors: P
authors: Chiari
authors: Geoffrey
authors: G
authors: Teixeira
authors: Elisabeth
authors: E
authors: Couture-Lepetit
authors: Maryline
authors: M
authors: Abrial
authors: Laurent
authors: L
authors: Argaud
authors: Abdallah
authors: A
authors: Gharib
authors: Michel
authors: M
authors: Ovize
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D057775:Ischemic Postconditioning / Q000379:methods; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009203:Myocardial Infarction / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology* / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D016572:Cyclosporine; D007530:Isoflurane