MEASUREMENT OF PLATELET-ACTIVATING-FACTOR IN A CANINE MODEL OF CORONARY-THROMBOSIS AND IN ENDARTERECTOMY SAMPLES FROM PATIENTS WITH ADVANCED CORONARY-ARTERY DISEASE

Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosp hocholine) is a potent phospholipid mediator of numerous inflammatory and thrombotic responses. The purpose of this study was to determine i f PAF synthesis is elevated in damaged coronary arteries after a susta ined period of cyclic flow variation (CEV), a phenomenon caused by alt ernating periods of thrombosis and reperfusion at sites of endothelial injury. Cyclic flow was established and maintained in the left anteri or descending coronary arteries (LADs) of 10 dogs. After 8 hours of CF V, the section of damaged LAD containing the thrombus and control sect ions of the circumflex artery, carotid artery, and saphenous vein was excised, and the total lipids were extracted. The PAF was then purifie d by silica column chromatography and high-performance liquid chromato graphy and assayed by both a rabbit platelet bioassay and a PAF radioi mmunoassay. With the platelet bioassay, PAF levels of 8.9 +/- 4.0 (ran ge, 4.8 to 15.5) pg/mg wet wt were found in the damaged LADs from the 10 dogs. This PAF bioactivity was completely inhibited by a PAF recept or antagonist. When the radioimmunoassay was used, slightly higher PAF levels of 16.3 +/- 12.9 (range, 4.5 to 41.8) pg/mg wet wt were observ ed in the LADs. Overall, these PAF levels were 3- to 63-fold higher th an in the control vessels when either assay method was used. Although increases in PAF were observed in the damaged LADs, measurements of PA F in blood samples taken from the LAD and the aorta (control) failed t o demonstrate any site-specific increase of PAF in the blood. In relat ed experiments, PAF was also measured in 23 endarterectomy samples tak en from the coronary arteries of 16 patients with severe atheroscleros is. The PAF levels in these samples were highly variable (2.9 +/- 2.2 [range, 0.3 to 8.5] pg/mg wet wt) and showed no correlation with tissu e mass, suggesting that PAF is affected by factors other than the simp le presence of atherosclerotic tissue in the vessel. These findings pr ovide direct evidence that PAF is synthesized locally at the site of e ndothelial injury during thrombosis and that PAF accumulates in the at herosclerotic plaque of some patients with advanced coronary artery di sease.