Effects of myocardial ischemia and reperfusion on mitochondrial function and susceptibility to oxidative stress |
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| Authors: | P Venditti P Masullo S Di Meo |
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| Institution: | (1) Department of General and Environmental Physiology, University of Naples 'Federico II', Via Mezzocannone 8, 80134 Napoli (Italy), Fax: + 39 081 2535090, e-mail: dimeo@biol.dgbm.unina.it , IT |
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| Abstract: | We investigated the effects of ischemia duration on the functional response of mitochondria to reperfusion and its relationship
with changes in mitochondrial susceptibility to oxidative stress. Mitochondria were isolated from hearts perfused by the Langendorff
technique immediately after different periods of global ischemia or reperfusion following such ischemia periods. Rates of
O2 consumption and H2O2 release with complex I- and complex II-linked substrates, lipid peroxidation, overall antioxidant capacity, capacity to remove
H2O2, and susceptibility to oxidative stress were determined. The effects of ischemia on some parameters were time dependent so
that the changes were greater after 45 than after 20 min of ischemia, or were significantly different to the nonischemic control
only after 45 min of ischemia. Thus, succinate-supported state 3 respiration exhibited a significant decrease after 20 min
of ischemia and a greater decrease after 45 min, while pyruvate malate-supported respiration showed a significant decrease
only after 45 min of ischemia, indicating an ischemia-induced early inhibition of complex II and a late inhibition of complex
I. Furthermore, both succinate and pyruvate malate-supported H2O2 release showed significant increases only after 45 min of ischemia. Similarly, whole antioxidant capacity significantly increased
and susceptibility to oxidants significantly decreased after 45 min of ischemia. Such changes were likely due to the accumulation
of reducing equivalents, which are able to remove peroxides and maintain thiols in a reduced state. This condition, which
protects mitochondria against oxidants, increases mitochondrial production of oxyradicals and oxidative damage during reperfusion.
This could explain the smaller functional recovery of the tissue and the further decline of the mitochondrial function after
reperfusion following the longer period of oxygen deprivation.
Received 18 May 2001; received after revision 17 July 2001; accepted 24 July 2001 |
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| Keywords: | , Ischemia-reperfusion, oxidative stress, hydrogen peroxide release, antioxidant capacity, mitochondrial function, |
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