Recombinant Tissue Plasminogen Activator Prevents Intimal Hyperplasia After Balloon Angioplasty in Hypercholesterolemic Rabbits

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Abstract
The purpose of this study was to clarify whether continuous infusion of recombinant tissue plasminogen activator (rtPA) prevents intimal hyperplasia at the site of arterial injury. Forty-three Kurosawa and Kusanagi hypercholesterolemic (KHC) rabbits which underwent balloon angioplasty of the right common iliac artery were randomly divided into 2 groups; rtPA for 7 days (n = 29) and untreated (n = 14). The former group was subdivided into a high-dose group (n = 15) (2 mg/kg per day continuously for 7 days after 3 mg/kg for 4h) and a low-dose group (n = 14) (0.6 mg/kg per day for 7 days after 0.6 mg/kg for 4 h). Balloon angioplasty was performed with a 2.5-mm balloon (3 x 60-sec, 6-atm inflations at 60-sec intervals) 1 h after the initiation of rtPA infusion via an ear vein. The iliac arteries of the rabbits were histologically studied at 28 days. The cross-sectional areas of the intima, media, and adventitia were calculated at the site of intimal hyperplasia. The intimal cross-sectional area was 0.07 +/- 0.11 (mean +/- SD) mm2 for the high-dose rtPA group and 0.11 +/- 0.07 mm2 for the low-dose rtPA group, and both of these values were significantly less than that for the control group (0.57 +/- 0.21 mm2 p < 0.01). The ratio of the intimal to medial cross-sectional area was significantly (p < 0.01) lower for the rtPA groups than for the control group (high-dose rtPA; 0.10 +/- 0.13, low-dose rtPA; 0.21 +/- 0.19, control; 1.25 +/- 0.55). In conclusion, continuous infusion of rtPA for 7 days prevented intimal hyperplasia after balloon injury.
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