Phospholipase activation has been suggested to represent one of the most relevant biochemical steps toward irreversible myocardial injury during ischemia. Accordingly, the time-course of myocardial phospholipid degradation was studied in 167 rats surviving coronary artery occlusion randomly divided into 83 controls and 84 treated with the phospholipase inhibitor quinacrine (75 mg/Kg s.c. every 8 h). The animals were sacrificed at different times ranging from 2 to 48 h post-occlusion and phospholipids and creatine kinase activity (CK) were measured on the supernatant of the left ventricular homogenates. In control animals a rapid fall in phospholipid concentration (from 1.33 +/- 0.12 to 0.67 +/- 0.05 microgram P/mg of protein) and CK activity (from 9.84 +/- 0.49 to 6.93 +/- 0.60 IU/mg of protein) was observed within 4 hours post-occlusion; these parameters remained almost unchanged throughout the rest of the study. In quinacrine-treated animals left ventricular phospholipids and CK also fell during the first hours post-occlusion; however, 24 and 48 h after the occlusion they were significantly higher than in controls (phospholipids: 0.99 +/- 0.05 vs 0.62 +/- 0.04 microgram P/mg of protein, p less than 0.001, and CK: 7.76 +/- 0.54 vs 4.99 +/- 0.37 IU/mg of protein, p less than 0.001, at 48 h). The effect of quinacrine on the extent of necrosis was then assessed in 13 anesthetized dogs undergoing ligation of the left anterior descending coronary artery. To measure the area at risk (RZ), 99Tc-PP labeled albumin microspheres were injected into the left atrium 5 min after coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)