trilinolein and Myocardial-Ischemia

In a previous study we demonstrated that trilinolein, a natural plant triacylglycerol, is a novel myocardial protective agent in vivo. The mechanism probably involves an antioxidant effect. This work investigated the mechanism of myocardial protection of trilinolein to determine if inhibition of calcium influx and alteration of activity of superoxide dismutase are involved. In isolated cardiomyocytes, pretreatment with trilinolein at a low concentration of 10(-9) M effectively reduced 45Ca2+ influx stimulated by hypoxia/normoxia by 34%. In isolated perfused rat heart subjected to 60 min global hypoxemia without reperfusion, pretreatment with 10(-7) M trilinolein for 15 min reduced infarct size by 37%. Assay of superoxide dismutase-mRNA by Northern blot analysis in in vivo rat heart subjected to 30 min ischaemia and 10 min reperfusion showed pretreatment with 10(-7) M trilinolein had a synergistic action with antioxidant systems preventing the rise in superoxide dismutase-mRNA. These results reconfirm the myocardial protection of trilinolein and suggest it may be related to antioxidant activity and inhibition of 45Ca2+ influx.

Topics: Animals; Blotting, Northern; Calcium; Calcium Radioisotopes; Cardiomyopathies; Male; Myocardial Infarction; Myocardial Ischemia; Myocardium; Oxygen; Plants, Medicinal; Rats; Rats, Sprague-Dawley; RNA, Messenger; Superoxide Dismutase; Triglycerides

Oxygen-derived free radicals (OFR) have been proposed as the cause of myocardial damage through lipid peroxidation during ischemia and reperfusion. Antioxidants can effectively ameliorate the damage induced by lipid peroxidation. Trilinolein is a triacylglycerol recently purified from the well known traditional Chinese herb Panax pseudoginseng, which has been used in treating circulatory disorders among Chinese for hundreds of years; it has linoleate as the only fatty acid residue in all three esterified positions of glycerol. This chemical has recently been demonstrated to have antioxidant activity by enhanced chemiluminescence. The addition of phorbol myristic acetate (PMA) to medium containing leukocytes produces OFR; this phenomenon was measured by chemiluminescence. Addition of trilinolein to medium containing leukocytes preceding the addition of PMA suppressed the production of OFR. The control value of chemiluminescence of a medium containing leukocytes with addition of PMA was 9.23 +/- 1.19 x 10(3) mV. The most effective concentration of trilinolein was 10(-7) mol/l which decreased the signals to 4.59 +/- 0.02 x 10(3) mV (p < 0.001). The antioxidant effect had a concentration-response curve similar to alpha-tocopherol. After pretreatment for 15 min with trilinolein at a concentration of 10(-7) mol/l in isolated perfused rat heart which had been subjected to 60 min of global ischemia, the integrity of the rat heart mitochondria was preserved as examined under the electron microscope. No swelling of mitochondria occurred and there was good alignment of cristae and absence of amorphous density. Previous experiments have shown that trilinolein can also improve erythrocyte deformability in vitro. Infarct size reduction of about 50% was also demonstrated in in vivo rat heart subjected to 4 h coronary occlusion. The mechanism of myocardial protection, in addition to the antioxidant effect, is suggested as maintaining the membrane fluidity of cardiomyocytes.

Topics: Animals; Antioxidants; In Vitro Techniques; Luminescent Measurements; Male; Mitochondria, Heart; Myocardial Ischemia; Myocardium; Platelet Aggregation Inhibitors; Rats; Rats, Sprague-Dawley; Triglycerides; Vitamin E