Relationship between lysophospholipid accumulation and plasma membrane injury during total in vitro ischemia in dog...

The relationship between alterations in tissue phospholipid composition and disruption of the plasma membrane during ischemia in dog heart was examined using a homogeneous in vitro model of total ischemia. This preparation was known to be associated with signs of membrane damage and was ideal for quantitation of phospholipid changes in ischemia because the weight of the tissue is unaffected by the duration of ischemia and because there is no collateral flow to remove the endproducts of phospholipid degradation. Measurements of phospholipid phosphate per gram of tissue confirmed that recovery of phospholipids and their degradation products was essentially complete in all samples including a sample taken after 24 h ischemia. The results showed that lysophospholipids gradually accumulated in the ischemic tissue; after 24 h in vitro ischemia, they comprised 12% of the total tissue phospholipids. Discontinuities of the plasma membrane were detected ultrastructurally in myocardium subjected to 150 min total ischemia, while under the same conditions, the lysophospholipid content amounted to less than 1% of the total tissue phospholipids. Phospholipid degradation was not limited by calcium availability since the rate of lysolipid production was not enhanced by incubation of myocardial tissue in a medium containing 1.25 mM calcium despite ultrastructural evidence of antecedent plasma membrane disruption. These data indicate that lysophospholipids accumulate in ischemic myocardium in the absence of collateral flow or inflammatory cell infiltration but that lysophospholipid accumulation occurs slowly and does not appear to be the dominant mechanism of plasma membrane fragmentation.