Lysoplasmenylethanolamine accumulation in ischemic/reperfused isolated fatty acid-perfused hearts.

Abstract

Lysophospholipid accumulation has been implicated in the pathogenesis of irreversible injury during myocardial ischemia and reperfusion. Plasmalogens (phospholipids with a vinyl-ether bond in the sn-1 position) account for more than 50%1 of total myocardial sarcolemmal and sarcoplasmic reticulum phospholipids. Accumulation of plasmalogen choline and ethanolamine lysophospholipids (lysoplasmenylcholine and lysoplasmenylethanolamine) or the effects of exogenous fatty acids on lysoplasmalogen accumulation during ischemia and reperfusion have not been examined. Isolated working rat hearts perfused with buffer containing either 11 mM glucose or 11 mM glucose plus 1.2 mM palmitate were subjected to aerobic, ischemic, or ischemia/reperfusion protocols. Levels of lysoplasmenylcholine and lysoplasmenylethanolamine were quantified using a two-stage high-performance liquid chromatographic technique. In hearts perfused with glucose alone, no significant differences in levels of lysoplasmenylcholine or lysoplasmenylethanolamine were seen during ischemia or reperfusion. In fatty acid-perfused hearts, however, significant accumulation of lysoplasmenylethanolamine occurred during reperfusion but not during ischemia (723+ 112, 734+83, and 1,394± 193 nmol/g dry wt for aerobic, ischemic, and ischemic/reperfused hearts, respectively; p<0.05 for ischemic/reperfused hearts versus aerobic or ischemic hearts). Lysoplasmenylcholine levels after ischemia and reperfusion did not differ significantly from aerobic values, regardless of whether fatty acids were present or absent from the perfusate. Aerobic and ischemic/reperfused rabbit hearts, in the presence of fatty acid, showed a similar profile in their lysoplasmalogen content. We conclude that differential lysoplasmenylethanolamine accumulation occurs during myocardial reperfusion when exogenous fatty acid concentrations are high. This may reflect the selective action of fatty acid intermediates on the metabolism of lysoplasmenylethanolamines. The role of lysoplasmalogens in producing the depressed mechanical recovery of fatty acid-perfused hearts after ischemia/reperfusion remains to be

Plasmalogen-Derived Lysolipid Induces a Depolarizing Cation Current in Rabbit Ventricular Myocytes

“…However, the majority of lysolipids in plasma are bound to protein. 23 In a protein-free bathing solution, the uptake of 10 mol/L [ 14 C]LPC in rat ventricular myocytes after a 60-minute incubation period 44 was comparable to tissue levels found during ischemia in cats, 45 rabbits, 38 dogs, 5,46 and humans. 39 Electrophysiological studies focusing on LPC have ignored the potential contribution of lysolipids derived from plasmalogens.…”

“…Many studies examining lysolipid content after ischemia did not report membrane LPLC content. 5,7,36,37 In rats, 38 rabbits, 38 dogs, 4 and humans, 39 no increases in total LPLC were found for up to 24 hours after myocardial ischemia. This is not surprising for the rat, in which choline plasmalogen content is Ͻ2% of choline phospholipids compared with 36% in humans.…”

Plasmalogens the neglected regulatory and scavenging lipid species

“…Therefore membrane dysfunction and defective contractility of the diabetic heart seem to be linked to high sarcolemmal levels of plasmalogens and an abnormal species distribution of glycerophospholipids (Vecchini et al, 2000). Likewise plasmalogens have also been shown to be selectively hydrolyzed during myocardial ischemia (Davies et al, 1992;Ford and Gross, 1989;Ford et al, 1991). This finding is especially interesting since the intercalation of amphipathic metabolites of phospholipolysis e.g., lysophosphatidylcholine into cardiac sarcolemma has been shown to have effects on the electrophysiological properties of heart cells (Corr et al, 1981;Katz and Messineo, 1981).…”

The role of nitric oxide in cardiac depression induced by interleukin‐1β and tumour necrosis factor‐α

“…(1967) was used, as previously described (Davies et at., 1992 After 20 min equilibration at 9.5 mmHg preload, the preload was altered between 5.5 and 15.5 mmHg in increments of 2 mmHg. Cardiac output, aortic pressure and coronary flow were measured at each interval in order to obtain a baseline ventricular function curve (referred to as t = 0 h).…”