title: Alterations in phospholipid metabolism in the globally ischemic rat heart: emphasis on phosphoinositide specific phospholipase C activity.
abstract: The effect of global ischemia on myocardial ventricular membrane phospholipids was evaluated using a modified Langendorff preparation. Isolated rat hearts were perfused at 37 degrees C with oxygenated Krebs Ringer solution or rendered ischemic by cessation of perfusion (10 min to 3 h). Longer periods of ischemia were assessed by incubating preperfused (10 min) intact hearts in non-oxygenated Krebs (37 degrees C) for 6 to 18 h. Ischemia-induced alterations in phosphatidylinositol levels and phosphoinositide-specific phospholipase C (PI PLC) activity were assessed in detail, since inositol phospholipids and PI-PLC play putative roles in the regulation of cell function and Ca2+ homeostasis. Decreases in major membrane phospholipids (phosphatidylcholine, phosphatidylserine, cardiolipin and sphingomyelin) were demonstrated after long ischemic periods (6 to 18 h). While periods of ischemia (3 h or less) induced no change in structural phospholipids, an elevation in lysophosphatidylcholine and free fatty acids was found by 1 h. Notably a significant increase in phosphatidylinositol content and an accompanying decrease in cytosolic PI PLC activity was detected by 30 mins of ischemia. Reduced enzymic activity was not due to altered in vitro activation or deactivation of PI-PLC, to a change in the Ca2+ requirement of the enzyme, or to translocation of the enzyme from the cytosol to a membrane fraction. The isolated rat heart made globally ischemic for 30 mins under conditions described for this investigation shows signs of irreversible injury i.e. increased cell Ca2+ content and inability to initiate and maintain rhythmic contraction upon reperfusion. Therefore, it is possible that altered phosphoinositide metabolism may contribute to the evolution of ischemia-elicited irreversible cell injury.
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago 60612.
authors.forename: D W
authors.initials: DW
authors.lastname: Schwertz
authors.forename: J
authors.initials: J
authors.lastname: Halverson
authors.forename: T
authors.initials: T
authors.lastname: Isaacson
authors.forename: H
authors.initials: H
authors.lastname: Feinberg
authors.forename: J W
authors.initials: JW
authors.lastname: Palmer
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003327:Coronary Disease / Q000201:enzymology / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D006352:Heart Ventricles / Q000201:enzymology / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D010716:Phosphatidylinositols; D010743:Phospholipids; D010738:Type C Phospholipases; D002118:Calcium