The rapid and reversible activation of a calcium-independent plasmalogen-selective phospholipase A₂ during myocardial ischemia

Recent studies have demonstrated the existence of two members of a novel family of calcium-independent plasmalogen-selective phospholipases A₂ in mammalian myocardium (Wolf, R. A., and R. W. Gross. 1985. J. Biol. Chem. 260:7295-7303; and Hazen, S. L., D. A. Ford, and R. W. Gross. 1991. J. Biol. Chem. 266:5629-5633). To examine the potential role of these calcium-independent phospholipases A₂ in mediating membrane dysfunction during early myocardial ischemia, the temporal course of alterations in phospholipase A₂ activity during global ischemia in Langendorf perfused rabbit hearts was quantified and compared with traditionally accepted markers of myocytic ischemic injury and anaerobic metabolism. We now report that membrane-associated calcium-independent plasmalogen-selective phospholipase A₂ activity increased over 400% during 2 min of global ischemia (P < 0.01), was near maximally activated (> 10-fold) after only 5 min of ischemia, and remained activated throughout the entire ischemic interval examined (2-60 min). Activation of membrane-associated plasmalogen-selective phospholipase A₂ after 5 min of myocardial ischemia was rapidly reversible during reperfusion of ischemic tissue. Both the activation of phospholipase A₂ and its reversibility during reperfusion were temporally correlated to alterations in myocytic anaerobic metabolism. Furthermore, activation of membrane-associated phospholipase A₂ was essentially complete before electron microscopic evidence of cellular damage. Collectively, these results identify dynamic alterations in calcium-independent plasmalogen-selective phospholipase A₂ activity during myocardial ischemia which precede irreversible cellular injury and demonstrate that activation of plasmalogen-selective phospholipase A₂ is amongst the earliest biochemical alterations in ischemic myocardium. (J. Clin. Invest. 1991. 88:331-335.) ischemic injury, phospholipid catabolism, plasmenylcholine, myocardium, Langendorf perfused hearts.