title: Role of phospholipases A2 and C in myocardial ischemic reperfusion injury.
abstract: We investigated the role of phospholipase A2 (PLA2) and phospholipase C (PLC) in myocardial phosholipid degradation and cellular injury during reperfusion of ischemic myocardium. For this purpose, isolated rat hearts were perfused with isotopic arachidonic acid to label its membrane phospholipids. Hearts preperfused with antiphospholipase A2 (anti-PLA2) retained a significantly higher amount of radiolabel in phosphatidylcholine and phosphatidylinositol and a corresponding lower amount of radiolabel in lysophosphatidylcholine and nonesterified fatty acids (P less than 0.05) after 30 min of reperfusion following 30 min of normothermic global ischemia compared with hearts preperfused with nonimmune immunoglobulin G. In similar experiments, antiphospholipase C (anti-PLC)-treated hearts were associated with significantly (P less than 0.05) higher radiolabel in all phospholipids and lower radiolabel in diacyglycerol compared with nonimmune immunoglobulin G-treated hearts. Measurement of phospholipase activity in subcellular organelles of these hearts showed decreased PLA2 activity in cytosol, mitochondria, and microsomes of anti-PLA2-treated hearts and decreased PLC activity of microsomes in anti-PLC-treated hearts. Furthermore, both the antiphospholipases attenuated the release of creatine kinase and lactate dehydrogenase into perfusate and increased contractility as well as coronary flow in the reperfused hearts. Results of this study suggest that both PLA2 and PLC are involved in the degradation of phospholipids and cellular injury that occur during reperfusion of ischemic myocardium.
authors.affiliation: Department of Surgery, University of Connecticut School of Medicine, Farmington 06032.
authors.forename: M R
authors.initials: MR
authors.lastname: Prasad
authors.forename: L M
authors.initials: LM
authors.lastname: Popescu
authors.forename: I I
authors.initials: II
authors.lastname: Moraru
authors.forename: X K
authors.initials: XK
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Maity
authors.forename: R M
authors.initials: RM
authors.lastname: Engelman
authors.forename: D K
authors.initials: DK
authors.lastname: Das
mesh_terms: D000818:Animals; D000906:Antibodies / Q000502:physiology; D003326:Coronary Circulation; D003327:Coronary Disease / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000378:metabolism; D010741:Phospholipases A / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D010738:Type C Phospholipases / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D016277:Ventricular Function, Left
chemical_list: D000906:Antibodies; D005230:Fatty Acids, Nonesterified; D010743:Phospholipids; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases