Relationship between oxidative stress and mitochondrial function in the post-conditioned heart

Abstract

The pathways activated by post-conditioning may converge on the mitochondria, in particular on the mitochondrial permeability transition pore. We sought to characterize the inhibition status of the mitochondrial permeability transition early after the post-conditioning maneuver and before long reperfusion was established. We observed that post-conditioning maneuvers applied to isolated rat hearts, after a prolonged ischemia and before reperfusion, promoted cardiac mechanical function recovery and maintained mitochondrial integrity. These effects were evaluated by mitochondrial swelling, calcium transport, and NAD⁺ content measurements; the improvements were established before restoring a long lasting reperfusion period. Mitochondrial integrity was associated with a diminution in oxidative stress, since carbonylation of proteins was prevented and aconitase activity was preserved in the post-conditioned hearts, implying that ROS might mediate mitochondrial dysfunction and mPTP opening. In addition, we found that cytochrome release was significantly abolished in the post-conditioned heart, in contrast with conventionally reperfused hearts.