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Protective effects of polysaccharide fucoidin on myocardial ischemia-reperfusion injury in rats
1Pharmaceutical Research Laboratory II, Suntory Institute for Biomedical Research, Osaka, Japan.
Abstract:
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.
Insights
Fucoidin, a polysaccharide, reduces heart damage after ischemia and reperfusion in rats. It works by blocking P-selectin, which prevents harmful neutrophil infiltration in the heart.
Area of Science:
- Cardiovascular Science
- Immunology
- Pharmacology
Background:
- Myocardial ischemia-reperfusion (I/R) injury is a significant clinical problem.
- Leukocyte adhesion and infiltration play a critical role in I/R injury.
- P-selectin is implicated in mediating leukocyte rolling and adhesion.
Purpose of the Study:
- To investigate the protective effects of fucoidin in a rat myocardial I/R injury model.
- To determine the role of P-selectin in mediating I/R injury and fucoidin's mechanism of action.
Main Methods:
- A rat model of 30-min myocardial ischemia and 6-h reperfusion was used.
- Fucoidin was administered intravenously at various time points.
- Myocardial infarct size was assessed using histological methods.
- P-selectin expression was determined immunohistochemically.
- Neutrophil infiltration was quantified by myeloperoxidase activity.
Main Results:
- Fucoidin significantly attenuated myocardial infarct size.
- P-selectin expression was observed on venular endothelial cells post-reperfusion.
- Neutrophil infiltration increased significantly after reperfusion.
- A 4-hour infusion of fucoidin reduced neutrophil infiltration, but a 2-hour infusion did not.
Conclusions:
- Neutrophil infiltration and myocardial injury in this model are linked to P-selectin expression.
- Fucoidin exerts protective effects by inhibiting P-selectin-mediated neutrophil rolling.
- Fucoidin demonstrates potential as a therapeutic agent for myocardial I/R injury.