A 7-day administration of tPA or heparin in the prevention of intimal hyperplasia following vascular injury in atherosclerotic rabbits.

The effects on intimal hyperplasia of tissue plasminogen activator (tPA) and heparin following vascular injury were investigated. A common iliac artery in 34 hereditary hypercholesterolemic rabbits was injured by three successive 60-second balloon inflations to a pressure of 6 atm. Thereafter, two groups were continuously infused with tPA for 7 days at rates of 2 mg/kg per 24 hours (tPA-H) or 0.6 mg/kg per 24 hours (tPA-L), and two groups received intraarterial infusions of 750 U/kg (heparin-H) or 150 U/kg (heparin-L) heparin, followed by 625 U/kg or 125 U/kg subcutaneously twice daily for the same period, respectively. Twenty-eight days after injury, the intimal areas of the tPA-H (0.07 +/- 0.13 mm2), tPA-L (0.11 +/- 0.08 mm2), heparin-H (0.17 +/- 0.08 mm2), and heparin-L (0.28 +/- 0.27 mm2) groups were all significantly (P < 0.01) smaller than the controls (0.57 +/- 0.23 mm2), as were the intimal/medial cross-sectional area ratios (0.10 +/- 0.14, 0.21 +/- 0.20, 0.28 +/- 0.10, and 0.50 +/- 0.54 vs 1.13 +/- 0.74, respectively). Thus, attenuation of platelet aggregation by tPA or heparin inhibited medial smooth muscle cell proliferation and intimal hyperplasia in balloon injured arteries.