MYOCARDIAL SALVAGE BY 1-O-HEXADECYL-SN-GLYCEROL - POSSIBLE ROLE OF PEROXISOMAL DYSFUNCTION IN ISCHEMIA-REPERFUSION INJURY

A recent study demonstrated biochemical and structural alterations of peroxisomes in rat kidney after ischemia/reperfusion. We examined whet her peroxisomes play any role in the pathophysiology of myocardial isc hemia/reperfusion injury. Isolated perfused rat heart was made ischemi c for 30 min by terminating coronary flow (CF), followed by 30-min rep erfusion. Experiments were divided into two groups; the experimental g roup received 1-O-hexadecyl-Sn-glycerol (chimyl alcohol) (25, 50, and 100 mu M) before ischemia, and the control group received an equivalen t amount of saline. Two of the experimental groups (50 and 100 mu M) d emonstrated improved postischemic myocardial performance, as demonstra ted by accelerated recovery in left ventricular developed pressure (LV DP) and CF, as well as reduction in the incidence of ventricular fibri llation (VF). However, because the heart rate (HR) was significantly r educed in the 100-mu M chimyl alcohol group, subsequent studies were p erformed with 50 mu M chimyl alcohol as the optimal dose. Chimyl alcoh ol (50 mu M) also reduced cellular injury, as evidenced by reduced cre atine kinase (CK) release, and decreased development of oxidative stre ss, as evidenced by reduced formation of malonaldehyde (MDA). Peroxiso mal catalase activity was decreased in the control group after ischemi a/reperfusion, and chimyl alcohol treatment restored the activity of t he enzyme. Our results indicate that chimyl alcohol, a precursor of et her-linked phosphoglyceride biosynthesis, can reduce myocardial ischem ia/reperfusion injury, possibly by restoring catalase activity and red ucing oxidative stress through synthesis of ether lipids, suggesting a possible role of peroxisomal disorder in ischemia/reperfusion injury.