2005 Fiscal Year Final Research Report Summary
Inhibitory effects of Sialyl Lewis^x oligosaccharide on reperfusion injury by avoidance of apoptosis
| Project/Area Number |
15591505
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | KURUME UNIVERSITY |
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Principal Investigator |
HAYASHIDA Nobuhiko Kurume University, School of Medicine, MD, 医学部, 講師 (30238141)
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| Co-Investigator(Kenkyū-buntansha) |
ARINAGA Koichi Kurume University, School of Medicine, MD, 医学部, 助手 (10299406)
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| Project Period (FY) |
2003 – 2005
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| Keywords | apoptosis / Sialyl Lewis^x / reperfusion injury / endothelial function / myocardial metabolism |
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| Research Abstract |
Object : Effects of supplemental Sialyl Lewis^x analogue, a major ligand for all three selectin family members, during warm blood cardioplegia were assessed in the blood perfused isolated rat heart. We evaluated the preservation of myocardial and endothelial function, and the avoidance of apoptosis.
Method : The blood-perfused isolated rat heart model was prepared with 20 Wistar rats. The isolated hearts were arrested for 60 min with warm blood cardioplegia given at 20-min intervals. This was followed by 60 min of reperfusion. The hearts were divided into the following two groups according to the supplemental drugs added to the cardioplegic solution. The control group (n=10) received standard warm blood cardioplegia. The SLX group (n=10) received warm blood cardioplegia supplemented with Sialyl Lewis^x analogue (60 μg/ml). Cardiac function, endothelial function, myocardial metabolism and myocardial myeroperoxidase activity were assessed before and after cardioplegic arrest. Tissue morph
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ology was examined by transmission electron microscopy. Apoptosis was determined by DNA fragmentation and TUNEL.
Result : Cardiac function was preserved better in the SLX group than the control group during reperfusion. C.flow and NO prod were greater in the SLX group than the control group when Ach.was added. MPO in myocardial tissue, expression of E-selectin and P-selectin in endthelium were lower in the SLX group than the control group. Transmission electron microscopy showed endothelial cell damage and appearance of apoptosis body in the control group, whereas such morphological change was less in the SLX group. DNA ladder and TUNEL-positive cell was shown in the control group. The results suggest that selectin-mediated endothelial-leukocyte interactions may play an important role in myocardial ischemia and reperfusion injury. Supplementation of Sialyl Lewis^x analogue during warm blood cardioplegia may provide superior myocardial protection by suppressing leukocyte-endothelial interaction and the avoidance of myocardial/endothelial apoptosis during early reperfusion period. Less
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