Heparin treatment enhances the recovery of neoendothelial acetylcholine-induced vascular relaxation after balloon catheter injury in the rabbit aorta.

ABSTRACT

BACKGROUND: After catheter injury, the neoendothelium that grows is abnormal in morphology and in acetylcholine-induced generation of endothelium-derived relaxing factor (EDRF). Heparin has been shown to have stimulatory effects on vascular endothelial growth in vitro. Its effect in vivo on neoendothelial cell morphology and metabolism after injury has not been described. We investigated the effect of heparin treatment on the neoendothelium formed after injury. METHODS AND RESULTS: Four groups of New Zealand White rabbits were studied. Group 1 rabbits underwent catheter denudation and were killed 4 weeks after injury without receiving treatment (NO Tx, n = 8). Groups 2 and 3 underwent similar aortic injury, received 2 weeks of treatment with either heparin (n = 7) or low molecular weight heparin (LMWH, n = 5), and were killed at 4 weeks. Group 4 underwent sham operation (SHAM, n = 8). EDRF generation was determined by the relaxation of precontracted aortic rings in an organ bath in response to acetylcholine. The heparin-treated group exhibited a significant improvement in acetylcholine-induced relaxation (27%) versus both LMWH-treated (14%, P = .035) and untreated groups (11%, P = .004), although relaxation was only 50% of that observed in the uninjured control vessels (52%, P = .001). The neoendothelium formed in the heparin-treated group exhibited a more normal histological appearance and was aligned with the direction of blood flow as compared with that observed in the untreated or LMWH-treated groups. CONCLUSIONS: These results demonstrate that in vivo heparin administration enhanced the recovery of EDRF generation and augmented normalization of the morphologic appearance of the neoendothelium.