1996 Fiscal Year Final Research Report Summary
The Effects of locally administered argatroban on restenosis after balloon angiopiasty
| Project/Area Number |
07670799
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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 |
Circulatory organs internal medicine
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| Research Institution | Nursing College, Wakayama Medical University (1996)
Wakayama Medical University (1995) |
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Principal Investigator |
ARITA Mikio Nursing College, Wakayama Medical University, Professor, 教授 (40168018)
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| Co-Investigator(Kenkyū-buntansha) |
TOMOBUCHI Yoshiaki Wakayama Medical College, Instructor, 講師 (30188809)
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| Project Period (FY) |
1995 – 1996
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| Keywords | intimal thickening / argatroban / local delivery |
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| Research Abstract |
This study was designed to elucidate the preventive effects of locally administered argatroban, a competitive inhibitor of thrombin, on restenosis after balloon angioplasty.
Experimental study : Japanese white rabbits weighing 2.1-2.5kg were used in this experiment. A hydrogel-coated balloon was immersed in argatroban/saline solution for 60 seconds three times, and was inflated at a pressure of 6atm, and left in the rabbit common carotid artery for 1 minute. The similar procedure was carried out, without drug, as a control. The pharmacokinetics of delivered argatroban in the arterial wall were assessed by HPLC and liquid scintilation counter. Platelet deposition 2 hours after balloon injury was observed by fluorescence study using antiplatelet antibody and scanning electron microscopy. Vascular smooth muscle cell (VSMC) proliferation 3 days after balloon injury was assessed by immunohistochemical staining using proliferating cell nuclear antigen (PCNA). In addition, intimal thickening 2
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0 days after ballooning was also examined. Results. The mean contents of argatroban immediately after ballooning and 2,6 hours after deflation were 24.63,0.49, and 0.11 nmole/gram wet weight of artery, respectively. Argatroban was undetected at 24 hours after deflation. Two hours after deflation, argatroban-treated arteries showed less platelet adhesion than saline-treated controls. The mean number of PCNA positive cells were 16.9% in argatroban and 43.8% in control groups (p<0.01), reflecting a significant suppressive effect on VSMC proliferation by argatroban. Intima-media area ratio 20 days after balloon injury were significantly smaller in the argatroban group with 1 and 0.1mg/ml than that in the argatroban group with 0.01mg/ml or saline-treated group, suggesting that locally administered argatroban inhibits intimal thickening in a rabbit injured carotid artery in a dose-dependent manner.
Clinical Study : We divided 50 elective PTCA patients into argatroban and control group. PTCA was performed using argatroban-immersed or -nonimmersed, hydrogel-coated balloon catheter with protective sheeth. Results. The mean late gain-loss was 8.2% in the argatroban group and 27.3% in the control group (p<0.05). The mean late restenosis rate was 11.1% in the argatroban group and 41.4% in control group (p<0.05).
Conclusions : These data suggest that blood coagulation plays an important role in VSMC proliferation after balloon injury and that locally administered argatroban using hydrogel-coated balloon prevents post-PTCA. Less
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