THE ROLE OF MITOCHONDRIA IN THE SALVAGE AND THE INJURY OF THE ISCHEMIC MYOCARDIUM

The relationships between mitochondrial derangements and cell necrosis are exemplified by the changes in the function and metabolism of mito chondria that occur in the ischemic heart. From a mitochondrial point of view, the evolution of ischemic damage can be divided into three ph ases. The first is associated with the onset of ischemia, and changes mitochondria from ATP producers into powerful ATP utilizers. During th is phase, the inverse operation of F0F1 ATPase maintains the mitochond rial membrane potential by using the ATP made available by glycolysis. The second phase can be identified from the functional and structural alterations of mitochondria caused by prolongation of ischemia, such as decreased utilization of NAD-linked substrates, release of cytochro me c and involvement of mitochondrial channels. These events indicate that the relationship between ischemic damage and mitochondria is not limited to the failure in ATP production. Finally, the third phase lin ks mitochondria to the destiny of the myocytes upon post-ischemic repe rfusion. Indeed, depending on the duration and the severity of ischemi a, not only is mitochondrial function necessary for cell recovery, but it can also exacerbate cell injury. (C) 1998 Elsevier Science B.V. Al l rights reserved.