Ultrastructural damage and Ca2+-shifts in the canine myocardium subjected to regional incomplete ischemia

Abstract

The role of Ca2+ in the pathogenesis leading to ischemic myocardial cell death is still controversial. To gain insight into this phenomenon a cytochemical procedure, the phosphate pyroantimonate method, was used to localize different subcellular Ca2(+)-pools at the ultrastructural level. After 45 min of left anterior descending coronary artery (LAD) occlusion, the coronary arteries were perfused with triphenyltetrazoliumchloride staining (TTC) to identify viable ischemic and infarcted tissue. In non-ischemic tissue, Ca2(+)-deposits were confined to the sarcolemma, sarcolemma-derived vesicles, transverse tubules, and intercalated disks. In infarcted tissue (TTC-negative), the sarcolemma lost its Ca2(+)-binding capacity and mitochondria were either overloaded with Ca2(+)-precipitate or they contained amorphous densities. In viable ischemic areas (determined with the TTC-technique) the sarcolemma was virtually devoid of Ca2(+)-deposits. Mitochondria in this area frequently showed clumping of the cristae, associated with an accumulation of Ca2(+)-precipitate in between the clustered cristae. The results of this study indicate that Ca2(+)-shifts occur in ischemic myocardial cells before the occurrence of other ultrastructural signs of irreversible injury which, therefore, narrows the possibility that Ca2(+)-overload is only a consequence of ischemic cell death.

NADH Oxidase Activity of Mitochondrial Apoptosis-inducing Factor

“…However, based on the present data, it is difficult to understand what the physiological function of AIF in normal (non-apoptotic) conditions may be. Since AIF is the only NADH oxidase detected in the intermembrane space, it is tempting to speculate that AIF accounts for the mitochondrial superoxide anion or hydrogen peroxide-generating NADH oxidase activity (54,55), which is lost from mitochondria, once cells have been induced to die (55). Clearly, an NADH oxidase activity causing the collateral generation of superoxide anion radicals would be of no advantage for the cell.…”

Global ischaemia induces a biphasic response of the mitochondrial respiratory chain. Anoxic pre-perfusion protects against ischaemic damage

“…Complexes I and III, are the major sources of free radicals produced by mitochondria in vitro [37]. NADH-dependent production of free radicals has been demonstrated cytochemically in the mitochondrial cristae of dog heart, this activity being low in normoxic tissue, markedly increased in viable ischaemic tissue and absent from severely infarcted regions [38]. This may be explained on the basis of a stimulation of free-radical production by Complex I, which is ultimately self-destructive, as these free radicals peroxidize cardiolipin.…”