Purpose: Thrombus formation enhances both neointima formation and clinical restenosis after vascular injury or angioplasty. Thrombotic occlusions and intimal hyperplasia limit the success of vascular reconstructive procedures. Thrombolysis is expected to improve the outcome for both restenosis and acute arterial occlusion after injury. Tissue-type plasminogen activator (tPA) is commonly used clinically, and it is thought to play a critical role in vascular remodeling by mediating intravascular clot lysis and modulating cell migration within the vessel wall. However, there is controversy about the late effects of tPA on the vascular lumen either for preventing or enhancing intima hyperplasia in vivo. Thus, this study was done to evaluate the impact of a clinical infusion of tPA on the neointima formation after a balloon injury.
Method: Forty male Sprague- Dawley rats weighting of 250∼300 gm each were underwent aortic intimal denuation with a 2F balloon catheter. The rats were divided into two groups: the control group (n=20: normal saline infusion), and the experiment group (n=20: intravenous injection of tPA; 0.15 mg/kg immediately after balloon injury, 0.75 mg/kg at 30 minutes after injury and, 0.50 mg/kg at 60 minutes after injury). The aortas were harvested at various time intervals (at 1, 5, 7 and 21 days) after the injury (n= 5: each time, respectively). The intima to media area ratio (IMAR) was evaluated microscopically, and the MMP expression was analyzed by using gelatin zymography.
Result: The mean IMAR on the 21st day was 1.14⁑0.16 in the control group and 1.10⁑0.11 in the experiment group. The mean IMAR was lower in the experiment group, but the result was not statistically significant. In comparison to the gelatinolytic activity of MMP-9 and, activated MMP-2, there was no significant difference between the two groups.
Conclusion: These results suggest that the effect of tPA on intimal hyperplasia after balloon injury to rat aorta showed minimal significance.
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