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.