Lysophosphoglycerides and ventricular fibrillation early after onset of ischemia

Lysophosphoglycerides accumulate in ischemic myocardium and induce electrophysiologic alterations in normoxic tissue in vitro closely analogous to those seen during ischemia in vivo. The present study was performed to define the temporal alterations of myocardial phospholipids during the first 3 minutes of ischemia in anesthetized cats and to determine whether the magnitude of the increase in lysophosphoglycerides correlates with the severity of ventricular arrhythmias. Fast-frozen transmural biopsies were obtained simultaneously from the ischemic and non-ischemic zones of the left ventricle. In control animals, values of lysophosphatidylcholine (LPC) did not differ in anterior (2.1±0.2 nmol/mg protein) compared with lateral (2.2±0.2 nmol/mg protein) regions of the left ventricular wall. The values for LPC in the anterior and lateral regions were also identical when expressed as % of total phospholipid phosphorus (1.4±0.1%). Comparing these values to those of all other animals biopsied within 3 minutes of ischemia, no significant increase in LPC was seen (1.7±0.2%). However, stratification of the animals based on the severity of ventricular arrhythmias showed striking differences. In animals without arrhythmias, no significant change occurred in LPC (1.2±0.2% phospholipid phosphorus or 2.0±0.3 nmol/mg protein) compared with the non-ischemic tissue control values (1.4±0.1% phospholipid phosphorus or 2.1±0.2 nmol/mg protein). In contrast, in animals with arrhythmias, a striking and significant increase in LPC (to 2.0±0.2% phospholipid phosphorus or 3.1±0.3 nmol/mg protein) was seen. Animals with unifocal and multifocal premature ventricular complexes but no ventricular fibrillation within 3 minutes of onset of ischemia demonstrated a significant but less marked increase in LPC (to 2.7±0.2 nmol/mg protein). In animals that developed spontaneous ventricular fibrillation within 2.3 minutes, the increase in LPC in the ischemic region was even greater (to 3.5±0.5 nmol/mg protein). Electrical induction of ventricular fibrillation 2 minutes after onset of ischemia in animals without arrhythmias did not elevate the lysophosphoglyceride values. The results indicate that ischemia can elicit significant increases of LPC in vivo within 3 minutes and that the severity of spontaneous ventricular arrhythmias is directly related to the magnitude of the increase. These results are discussed relative to previous findings and areas requiring future investigation are outlined.