Role of iron on membrane phospholipid breakdown in ischemic-reperfused rat heart.
Oxygen-derived free radicals have been implicated in causing degradation of myocardial membrane phospholipids associated with ischemia and reperfusion. Since iron is known to catalyze the hydroxyl radical formation responsible for cellular injury, this study was designed to relate the role of iron with phospholipid breakdown in ischemic-reperfused heart. Isolated rat heart perfused by the Langendorff technique was subjected to 30 min of normothermic ischemia followed by 30 min of reperfusion. The experimental group received 0.6 mM deferoxamine, an iron chelator, before reperfusion of ischemic myocardium. Deacylation and reacylation of membrane phospholipids were monitored by using [14C]arachidonic acid (AA), whereas the de novo phospholipid synthesis was evaluated by using [3H]glycerol in the perfusate. In the deferoxamine group, the loss of [14C]phosphatidylcholine (PC) and the corresponding accumulation of isotopic lysophosphoglycerides as well as AA was significantly lower compared with the control. The incorporation of radioactivity for [14C]AA and [3H]glycerol into phospholipids was significantly increased in the treated group compared with the untreated group. In addition, decreased malonaldehyde formation and lactate dehydrogenase release, a higher recovery of high-energy phosphate compounds, and myocardial contractility were noticed in the deferoxamine-treated hearts. These results indicated that postischemic administration of an iron chelator such as deferoxamine can preserve membrane phospholipids and reduce myocardial dysfunction associated with reperfusion of ischemic heart.
Liu
X K
XK
Department of Surgery, University of Connecticut School of Medicine, Farmington 06032.
Prasad
M R
MR
Engelman
R M
RM
Jones
R M
RM
Das
D K
DK
D000215:Acylation; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D003676:Deferoxamine / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006321:Heart / Q000503:physiopathology; D006352:Heart Ventricles; D006900:Hydroxylation; D007501:Iron / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D005230:Fatty Acids, Nonesterified; D008563:Membrane Lipids; D010710:Phosphates; D010743:Phospholipids; D007501:Iron; D007770:L-Lactate Dehydrogenase; D003676:Deferoxamine