Protective effects of polysaccharide fucoidin on myocardial ischemia-reperfusion injury in rats.
We tested whether polysaccharide fucoidin, which inhibits leukocyte rolling in the mesenteric venule, has protective effects in the rat myocardial 30-min ischemia and 6-h reperfusion injury model. Intravenous infusion of fucoidin (27 microg/kg/min from 10 min before to 6 h after reperfusion) significantly attenuated myocardial infarct size 6 h after reperfusion. In this ischemia and reperfusion heart model, expression of P-selectin (determined immunohistochemically) was observed on the venular endothelial cells in the heart 30 min after reperfusion and also was sustained after 6 h. Neutrophil infiltration as estimated by myeloperoxidase activity significantly increased 2 h after reperfusion and kept increasing with time until 6 h after reperfusion. Four-hour infusion of fucoidin after reperfusion significantly reduced neutrophil infiltration, whereas the 2-h infusion of fucoidin did not. These results indicate that neutrophil infiltration and myocardial injury are attributed to expression of P-selectin after reperfusion, and that one of the inhibitory mechanisms of fucoidin seems to be blockade of P-selectin-mediated neutrophil rolling on the vessel wall.
Omata
M
M
Pharmaceutical Research Laboratory II, Suntory Institute for Biomedical Research, Osaka, Japan.
Matsui
N
N
Inomata
N
N
Ohno
T
T
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D007150:Immunohistochemistry / Q000379:methods; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D008643:Mesentery / Q000098:blood supply; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D019007:P-Selectin / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D014699:Venules / Q000187:drug effects / Q000473:pathology
D000925:Anticoagulants; D019007:P-Selectin; D011134:Polysaccharides; C007789:fucoidan; D009195:Peroxidase