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 whether peroxisomes play any role in the pathophysiology of myocardial ischemia/reperfusion injury. Isolated perfused rat heart was made ischemic for 30 min by terminating coronary flow (CF), followed by 30-min reperfusion. Experiments were divided into two groups; the experimental group received 1-O-hexadecyl-Sn-glycerol (chimyl alcohol) (25, 50, and 100 microM) before ischemia, and the control group received an equivalent amount of saline. Two of the experimental groups (50 and 100 microM) demonstrated improved postischemic myocardial performance, as demonstrated by accelerated recovery in left ventricular developed pressure (LVDP) and CF, as well as reduction in the incidence of ventricular fibrillation (VF). However, because the heart rate (HR) was significantly reduced in the 100-microM chimyl alcohol group, subsequent studies were performed with 50 microM chimyl alcohol as the optimal dose. Chimyl alcohol (50 microM) also reduced cellular injury, as evidenced by reduced creatine kinase (CK) release, and decreased development of oxidative stress, as evidenced by reduced formation of malonaldehyde (MDA). Peroxisomal catalase activity was decreased in the control group after ischemia/reperfusion, and chimyl alcohol treatment restored the activity of the enzyme. Our results indicate that chimyl alcohol, a precursor of ether-linked phosphoglyceride biosynthesis, can reduce myocardial ischemia/reperfusion injury, possibly by restoring catalase activity and reducing oxidative stress through synthesis of ether lipids, suggesting a possible role of peroxisomal disorder in ischemia/reperfusion injury.
Maulik
N
N
Department of Surgery, University of Connecticut School of Medicine, Framington 06030-1110.
Tosaki
A
A
Engelman
R M
RM
Cordis
G A
GA
Das
D K
DK
D015104:3,4-Methylenedioxyamphetamine / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D005995:Glyceryl Ethers / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008830:Microbodies / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D014693:Ventricular Fibrillation / Q000188:drug therapy
D005995:Glyceryl Ethers; D015104:3,4-Methylenedioxyamphetamine; D002374:Catalase; D003402:Creatine Kinase; C004348:chimyl alcohol