lysophosphatidylethanolamine and Coronary-Disease

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.

Topics: Animals; Cell Membrane; Coronary Disease; Diffusion; Dogs; Female; In Vitro Techniques; Inulin; Lysophosphatidylcholines; Lysophospholipids; Male; Microscopy, Electron; Myocardium; Phosphatidylethanolamines; Phospholipids

This study was performed to determine the early and delayed metabolic effects of myocardial ischemia on the major membrane phospholipids and to reassess the potential role of lysophospholipids in the genesis of malignant dysrhythmias induced by ischemia. Samples taken from in situ hearts before ant at various intervals up to 40 minutes after abrupt ligation of LAD were extracted by the classical Folch technique with modifications to avoid artifactual lysophospholipid production and losses. Following thin layer chromatography of lipid extracts, phospholipid fractions were quantified by phosphorus estimation and lysophospholipids by a more sensitive method employing gas liquid chromatography. The total phospholipid content with the exception of lysophospholipids remained essentially constant throughout the early phases of acute ischemia, but fell by 6 and 14% after 8 and 24 ours, respectively. At 8 minutes, lysophospholipid levels n ischemic myocardium were significantly increased by 60% compared to pre-occlusion controls in the ischemic zone and by 25% in post-occlusion controls. They changed little thereafter. The molecular species of lysophospholipids remained unchanged throughout the period of ischemia studied. The mole fraction of other phospholipids as well as their fatty acyl and aldehyde profiles also were unchanged. Despite significant elevations in lysophospholipids levels, their absolute quantities were very small (0.6% of total phospholipid P) and 15-fold smaller than that reported in vitro to simulate electrophysiological manifestation of ischemia. However, such small amounts in vivo, if produced in the microenvironment of certain membrane-bound enzymes along with acidosis, hypoxia, and fatty acids, could be potentially deleterious to cell functions.

Topics: Animals; Coronary Disease; Lysophosphatidylcholines; Lysophospholipids; Myocardium; Phosphatidylcholines; Phosphatidylethanolamines; Phospholipids; Plasmalogens; Swine; Time Factors