Abstract |
Reperfusion injury is related closely to inflammatory reactions such as the activation and accumulation of neutrophils. We investigated the efficacy of a novel small molecule selectin antagonist ( bimosiamose) in a rat model of transient left coronary artery occlusion (30 min) and reperfusion (24 h). Treatment with bimosiamose (25 mg/kg, intravenously at reperfusion) showed a significant reduction in infarction area/area at risk of approximately 41% compared to vehicle control (P=0.01) and preserved the left ventricular function. The accumulation of polymorphonuclear neutrophils at the site of area at risk was decreased significantly, accompanied by 78% reduction of the myeloperoxidase activity. Parallel-plate flow chamber analysis revealed that bimosiamose showed a significant inhibition in rolling (62%, P<0.001) and adhesion (38%, P<0.05) of HL-60 cells to activated human umbilical vein endothelial cells compared with vehicle control. This study demonstrates for the first time that bimosiamose, a novel small molecule selectin antagonist, attenuates significantly ischemia/reperfusion injury.
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Authors | Yasuyuki Onai, Jun-ichi Suzuki, Yasunobu Nishiwaki, Ryo Gotoh, Kurt Berens, Richard Dixon, Masayuki Yoshida, Hiroshi Ito, Mitsuaki Isobe |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 481
Issue 2-3
Pg. 217-25
(Nov 28 2003)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 14642789
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Biphenyl Compounds
- Mannosides
- Selectins
- bimosiamose disodium
- Mannose
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Topics |
- Animals
- Biphenyl Compounds
(pharmacology, therapeutic use)
- Cells, Cultured
- HL-60 Cells
- Humans
- Male
- Mannose
(analogs & derivatives)
- Mannosides
(pharmacology, therapeutic use)
- Myocardial Ischemia
(pathology, prevention & control)
- Myocardial Reperfusion Injury
(pathology, prevention & control)
- Neutrophils
(drug effects)
- Rats
- Rats, Sprague-Dawley
- Selectins
(physiology)
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