Journal
ARCHIVES OF MEDICAL SCIENCE
Volume 9, Issue 6, Pages 968-975Publisher
TERMEDIA PUBLISHING HOUSE LTD
DOI: 10.5114/aoms.2013.38175
Keywords
cyclosporine A; infarct size; ischemic postconditioning; mitochondrion; myocardial ischemia/reperfusion
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Funding
- German Research Foundation [He1320/18-1]
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Introduction: Ischemic postconditioning (PoCo) and cyclosporine A (CysA) given prior to reperfusion reduce myocardial infarct size after ischemia/reperfusion. Ischemic postconditioning's protection is characterized by better preservation of mitochondrial respiration and calcium retention capacity. Protection by CysA is not entirely clear. Cyclosporine A inhibits not only mitochondrial permeability transition pore (mPTP) opening but also the phosphatase calcineurin. We have investigated whether CysA mediates protection not only by mPTP inhibition but also through a more upstream inhibition of calcineurin with subsequently better preserved mitochondrial respiration. Material and methods: Anesthetized pigs were subjected to 90 min ischemia and 10 min reperfusion initiated with either PoCo (6 x 20 s reperfusion/re-occlusion; n = 9), CysA infusion (5 mg/kg iv.; 5 min before reperfusion; n = 4), or immediate full reperfusion (IFR; n = 8). Mitochondria were isolated from myocardial tissue for measurement of respiration and calcium retention capacity. Results: In mitochondria from ischemic/reperfused myocardium, ADP-stimulated complex I respiration was similar between CysA (116 +/- 11 nmol O-2/min/mg protein) and 4FR (117 +/- 8), but better preserved with PoCo (160 +/- 9; p < 0.05). Calcium retention capacity was greater with both PoCo and CysA (1096 +/- 45 and 1287 +/- 128 nmol Ca2+/mg protein) than with IFR (756 +/- 103; p < 0.05). Conclusions: Cyclosporine A's protection is not associated with improved mitochondria! respiration. Protection is unlikely related to an upstream calcineurin inhibition, but is indeed secondary to mPTP inhibition.
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