Davies N J, Schulz R, Olley P M, Strynadka K D, Panas D L, Lopaschuk G D
Department of Medicine, University of Alberta, Edmonton, Canada.
Circ Res. 1992 Jun;70(6):1161-8. doi: 10.1161/01.res.70.6.1161.
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% 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
溶血磷脂的蓄积与心肌缺血再灌注期间不可逆损伤的发病机制有关。缩醛磷脂(在sn-1位带有乙烯醚键的磷脂)占心肌肌膜和肌浆网总磷脂的50%以上。尚未研究缺血再灌注期间缩醛磷脂胆碱和乙醇胺溶血磷脂(溶血缩醛磷脂酰胆碱和溶血缩醛磷脂酰乙醇胺)的蓄积或外源性脂肪酸对溶血缩醛磷脂蓄积的影响。用含11 mM葡萄糖或11 mM葡萄糖加1.2 mM棕榈酸的缓冲液灌注离体工作大鼠心脏,使其经历有氧、缺血或缺血/再灌注方案。采用两阶段高效液相色谱技术对溶血缩醛磷脂酰胆碱和溶血缩醛磷脂酰乙醇胺的水平进行定量。在仅用葡萄糖灌注的心脏中,缺血或再灌注期间溶血缩醛磷脂酰胆碱或溶血缩醛磷脂酰乙醇胺的水平无显著差异。然而,在脂肪酸灌注的心脏中,溶血缩醛磷脂酰乙醇胺在再灌注期间显著蓄积,但在缺血期间未蓄积(有氧、缺血和缺血/再灌注心脏分别为723±112、734±83和1394±193 nmol/g干重;缺血/再灌注心脏与有氧或缺血心脏相比,p<0.05)。无论灌注液中是否存在脂肪酸,缺血再灌注后的溶血缩醛磷脂酰胆碱水平与有氧时的值无显著差异。在有脂肪酸存在的情况下,有氧和缺血/再灌注的兔心脏在其溶血缩醛磷脂含量方面表现出相似的特征。我们得出结论,当外源性脂肪酸浓度较高时,心肌再灌注期间会发生溶血缩醛磷脂酰乙醇胺的差异蓄积。这可能反映了脂肪酸中间体对溶血缩醛磷脂酰乙醇胺代谢的选择性作用。(摘要截短于250字)