title: Role of membrane phospholipids in myocardial injury induced by ischemia and reperfusion.
abstract: Depletion of membrane phospholipids is known to be associated with myocardial ischemia, but its relationship to the injury involved with the reperfusion of ischemic myocardium is not known. The present study was designed to relate phospholipid degradation with reperfusion injury. The isolated in situ pig heart was subjected to 60 min of regional ischemia induced by occluding the left anterior descending (LAD) coronary artery and 60 min of global ischemia by hypothermic cardioplegic arrest followed by 60 min of reperfusion. The pigs were divided into two groups. In the treatment group, the heart was preperfused with mepacrine (0.05 mM), a known phospholipase inhibitor, for 15 min prior to LAD occlusion. In the control group, the total phospholipid content was not significantly decreased during LAD occlusion and arrest, but was reduced appreciably after reperfusion. Phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol followed a similar pattern. The lowering of these phospholipids during reperfusion was accompanied by enhancement of lysophosphatidylcholine. Mepacrine restored the normal levels of these phospholipids. During reperfusion, fatty acyl CoA synthetase, lysophospholipase, and lysophosphatidylcholine acyltransferase were depressed, whereas phospholipase A2 was enhanced. Mepacrine inhibited phospholipase A2, but had no effects on the other enzymes. Mepacrine also provided significant protection against reperfusion injury, as documented by the preservation of high-energy phosphate compounds and inhibition of the appearance of creatine kinase activity in the perfusate. These results suggest that membrane phospholipids play an important role in myocardial injury associated with ischemia and reperfusion, primarily because the deacylation-reacylation cycle of phospholipid biosynthesis becomes defective.
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000037:antagonists & inhibitors; D000215:Acylation; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003066:Coenzyme A Ligases / Q000378:metabolism; D003327:Coronary Disease / Q000201:enzymology / Q000473:pathology*; D003402:Creatine Kinase / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006323:Heart Arrest / Q000201:enzymology / Q000473:pathology; D007527:Isoenzymes; D008245:Lysophospholipase / Q000378:metabolism; D008563:Membrane Lipids / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology; D010477:Perfusion; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000502:physiology*; D011796:Quinacrine / Q000494:pharmacology; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D013552:Swine; D013997:Time Factors; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D007527:Isoenzymes; D008563:Membrane Lipids; D010743:Phospholipids; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D008243:1-Acylglycerophosphocholine O-Acyltransferase; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D003402:Creatine Kinase; D010741:Phospholipases A; D054467:Phospholipases A2; D008245:Lysophospholipase; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase; D011796:Quinacrine