Korean Circ J.  2005 Jan;35(1):15-21. 10.4070/kcj.2005.35.1.15.

LB30057, a Direct Thrombin Inhibitor, the Effect of Restenosis in Porcine Coronary Injury Model

Affiliations
  • 1Department of Cardiology, Wonju College of Medicine, Yonsei University, Wonju, Korea. yoonj@wonju.yonsei.ac.kr
  • 2Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju, Korea.
  • 3LG Chemical, Daejeon, Korea.

Abstract

BACKGROUND AND OBJECTIVES
In a previous study, LB30057 was found to inhibit smooth muscle cell proliferation in a dose dependent manner, and prolonged 1 4-day oral administration of LB30057 is effective in reducing the neointimal hyperplasia in a rat carotid balloon injury model. The prolonged administration of LB30057, an orally active direct thrombin inhibitor, was evaluated and found to be a potential inhibitor of restenosis in a porcine coronary injury model.
MATERIALS AND METHODS
An oversized balloon injury and a stent injury were given to the right coronary artery and left anterior descending artery, respectively, in the porcine model. LB30057 (50mg/kg) or a placebo was administrated for 28 days, using an osmotic pump, starting 6 hours prior to the injury until sacrifice on the 28th day. The drug concentration and antithrombotic effects (aPTT, thrombin-anti thrombin complex levels) were measured, and a histo-morphometric analysis performed 28 days later.
RESULTS
The drug concentrations were 271+/-1 24 and 67+/-52 ng/mL on days 1 and 28 after injury in the drug group. The TAT (thrombin-antithrombin complex) levels were significantly lower in the drug than the control group on the 2nd and 7th days after injury (p<0.05). There were no significant differences in the injury scores, and the luminal, intimal and medial areas between the two groups.
CONCLUSION
Prolonged administration of LB30057, using an osmotic pump, was not effective in reducing the restenosis in our pig coronary injury model.

Keyword

Thrombin; Coronary restenosis; Coronary disease

MeSH Terms

Administration, Oral
Animals
Arteries
Coronary Disease
Coronary Restenosis
Coronary Vessels
Hyperplasia
Myocytes, Smooth Muscle
Phenobarbital
Rats
Stents
Thrombin*
Phenobarbital
Thrombin
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