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10.1016/j.athoracsur.2008.06.033

http://scihub22266oqcxt.onion/10.1016/j.athoracsur.2008.06.033
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suck abstract from ncbi


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pmid18805178
      Ann+Thorac+Surg 2008 ; 86 (4 ): 1286-92
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  • Cyclosporine preserves mitochondrial morphology after myocardial ischemia/reperfusion independent of calcineurin inhibition #MMPMID18805178
  • Leshnower BG ; Kanemoto S ; Matsubara M ; Sakamoto H ; Hinmon R ; Gorman JH 3rd ; Gorman RC
  • Ann Thorac Surg 2008[Oct]; 86 (4 ): 1286-92 PMID18805178 show ga
  • BACKGROUND: Opening of the mitochondrial permeability transition pore (MPTP) has been shown to contribute to myocardial ischemia/reperfusion injury. We sought to demonstrate that the myocardial protective effect of inhibiting MPTP opening with cyclosporine A (CsA) results in stabilization of mitochondrial morphology and is independent of CsA-induced calcineurin inhibition. METHODS: Thirty-seven rabbits were divided into three groups: control (n = 15), CsA (MPTP and calcineurin inhibitor, n = 12), or FK506 (calcineurin inhibitor, n = 10). Each group received a 1-hour infusion of either a saline vehicle, 25 mg/kg CsA or 1 mg/kg FK506. All animals underwent 30 minutes of regional ischemia and 3 hours of reperfusion. Myocardial infarct size was determined using Evans blue dye and triphenyltetrazolium chloride. In situ oligo ligation was used to assess apoptotic cell death. Transmission electron microscopy was used to quantitatively evaluate morphologic differences in the mitochondria between groups. RESULTS: Infarct size in the CsA group (39% +/- 3%) was significantly reduced compared with the control group (60% +/- 2%, p < 0.001) and FK506 group (55% +/- 3%, p = 0.001). Apoptotic cell death was also attenuated in the CsA group (1.2% +/- 0.5%) compared with the control group (4.3% +/- 0.8%, p = 0.01) and FK506 group (4.1% +/- 0.9%, p = 0.05). Transmission electron microscopy revealed a preservation of normal mitochondrial morphology and a reduction in the percentage of disrupted mitochondria in the CsA group (20% +/- 7%) compared with the control group (53% +/- 12%) and FK506 group (47% +/- 9%). CONCLUSIONS: Cyclosporine A-induced MPTP inhibition preserves mitochondrial morphology after myocardial ischemia/reperfusion and limits myocyte necrosis and apoptosis. These effects are independent of calcineurin inhibition.
  • |Analysis of Variance [MESH]
  • |Animals [MESH]
  • |Calcineurin/drug effects/*metabolism [MESH]
  • |Cyclosporine/*pharmacology [MESH]
  • |Disease Models, Animal [MESH]
  • |Immunohistochemistry [MESH]
  • |Ischemic Preconditioning, Myocardial/methods [MESH]
  • |Male [MESH]
  • |Mitochondria, Muscle/drug effects/pathology [MESH]
  • |Mitochondrial Membrane Transport Proteins/*drug effects/metabolism [MESH]
  • |Mitochondrial Permeability Transition Pore [MESH]
  • |Myocardial Infarction/drug therapy/metabolism [MESH]
  • |Myocardial Ischemia/*drug therapy/metabolism [MESH]
  • |Myocardial Reperfusion Injury/pathology/*prevention & control [MESH]
  • |Myocardial Reperfusion/methods [MESH]
  • |Probability [MESH]
  • |Rabbits [MESH]
  • |Random Allocation [MESH]
  • |Sensitivity and Specificity [MESH]


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