Prevention by amiodarone of phospholipid depletion in isoproterenol-induced ischemia in rats.
This work was performed to study phospholipid metabolism in isoproterenol-induced ischemic heart and the possible protective effect of amiodarone (Am) and chlorpromazine (CPZ). Heart weight increased 24 h after subcutaneous injection of isoproterenol (40 mg/kg) whereas myocardial phospholipid content and creatine kinase activity decreased without modification of the cholesterol content. The phospholipid content was significantly correlated with creatine kinase activity (P less than 0.001). Phosphatidylcholine, phosphatidylethanolamine and cardiolipin decreased significantly (P less than 0.001) in the isoproterenol group whereas the lysophosphatidylcholine and lysophosphatidylethanolamine content increased. The lysophosphatidylcholine/phosphatidylcholine and lysophosphatidylethanolamine/phosphatidylethanolamine ratios consequently increased to a significant degree (P less than 0.01) suggesting indirectly the activation of phospholipases A in the ischemic myocardium. Free fatty acid content increased, indicating hydrolysis of phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine and lysophosphatidylethanolamine. Intravenous injection of Am (20 mg/kg) or intraperitoneal injection of CPZ (30 mg/kg) prior to isoproterenol injection provided complete protection against phospholipid depletion and against increase of the lysophosphatidylcholine/phosphatidylcholine and lysophosphatidylethanolamine/phosphatidylethanolamine ratios which returned to control values. Neither substance had any effect on the heart weight increase due to an edematous and inflammatory process. The total protection by both substances against phospholipid depletion was not sufficient to prevent the creatine kinase activity decrease. The improved phospholipid degradation in the ischemic myocardium is discussed in relation to the in vitro inhibitory effect of Am or CPZ on phospholipases A activity.
Sanofi, Centre de Recherche Labaz-Sanofi, Bruxelles, Belgium.
P
P
Chatelain
M
M
Gremel
R
R
Brotelle
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism; D003327:Coronary Disease / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D003402:Creatine Kinase / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D010743:Phospholipids / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D010743:Phospholipids; D011506:Proteins; D002784:Cholesterol; D003402:Creatine Kinase; D007545:Isoproterenol; D000638:Amiodarone; D002746:Chlorpromazine