Inhibition of ischemia-induced phospholipase activation by quinacrine protects jeopardized myocardium in rats with coronary artery occlusion.
Phospholipase activation has been proposed as one relevant biochemical step toward irreversible myocardial injury during ischemia. Accordingly, after coronary artery occlusion, the time course of myocardial phospholipid degradation was studied in 83 control rats and 84 rats treated with quinacrine (75 mg/kg s.c. every 8 hr), a phospholipase inhibitor. Animals were sacrificed at different times ranging from 2 to 48 hr postocclusion. In controls a rapid fall in left ventricular phospholipid concentration (from 1.33 +/- 0.12 to 0.67 +/- 0.05 micrograms of P/mg of protein) and creatinkinase (CK) activity (from 9.84 +/- 0.49 to 6.93 +/- 0.60 I.U./mg of protein) was observed within 4 hr postocclusion. In quinacrine-treated animals phospholipids and CK also fell initially; however, 24 and 48 hr after occlusion they were higher than in controls (phospholipids: 0.99 +/- 0.05 vs. 0.62 +/- 0.04 micrograms of P/mg of protein, P less than .001; CK: 7.76 +/- 0.54 vs. 4.99 +/- 0.37 I.U./mg of protein, P less than .001, at 48 hr). Additional rats surviving coronary occlusion were divided randomly into a control (n = 14) and three treated groups receiving quinacrine every 8 hr at the dose of 5 (n = 13), 20 (n = 13) or 75 mg/kg (n = 15); 13 rats were sham-operated. Forty-eight hours postocclusion myocardial phospholipids were measured and infarct size calculated by CK depletion. Infarct size was significantly smaller in high dose quinacrine-treated than in control rats (16.6 +/- 5.7 vs. 42.1 +/- 4.4% of left ventricle, P less than .001). In treated animals, myocardial phospholipid concentration was also significantly higher.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000201:enzymology* / Q000473:pathology; D003402:Creatine Kinase / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D007527:Isoenzymes; D008297:Male; D008433:Mathematics; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology; D009206:Myocardium / Q000201:enzymology*; D010740:Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011796:Quinacrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D007527:Isoenzymes; D010743:Phospholipids; D003402:Creatine Kinase; D010740:Phospholipases; D011796:Quinacrine