EFFECTS OF THERMAL EXPOSURE ON BINDING OF HEPARIN IN-VITRO TO THE ARTERIAL-WALL AND TO CLOT AND ON THE CHRONIC ANGIOGRAPHIC LUMINAL RESPONSE TO LOCAL APPLICATION OF A HEPARIN FILM DURING ANGIOPLASTY IN AN IN-VIVO RABBIT MODEL

Experimentally, heparin inhibits mechanisms that promote fibrosis, neo intimal cellular proliferation, and thombin bound to fibrin at the sur face of intraluminal thrombus, but only in relatively high concentrati ons. A preliminary hypothesis was tested and confirmed in vitro that i nitial binding of H-3-heparin to mechanically injured porcine aorta is concentration-dependent over a 1,000-50,000 units/ml range (r = 0.9). The hypothesis was then tested in vitro that thermal exposure during contact of heparin to arterial tissue and to clot would enhance bindin g of the drug. H-3-heparin binding to clot, whole blood particulates, and washed erythrocytes was markedly enhanced by exposure to temperatu res > 70-degrees-C. Thermal exposure (80-degrees-C X 40 s) also enhanc ed tissue persistence of the drug within porcine aorta subjected to a shear rate of 1,100-1 in an annular Baumgartner chamber perfused with normal saline at 37-degrees-C for 48 h. Heparin in vitro anticoagulant activity persisted after thermal exposure and binding to tissues. A n ew method was developed for local application of a heparin film that p rovides a maximum concentration with a tolerable systemic dose during an angioplasty procedure. In an in vivo rabbit model of mural fibrosis after iliac artery angioplasty, the 1-month mean angiographic luminal diameter loss (23% compared to the acute postangioplasty result by co mputer image analysis) in response to conventional balloon angioplasty (BA) and laser balloon angioplasty (LBA) was the same (P > 0.05). Loc al application of a heparin film (3,000 units at a concentration > 100 ,000 units/g), however, reduced the mean % loss in diameter 1 month af ter LBA (12%), but not after BA (29%), compared to arteries subjected to angioplasty without local heparin (P < .05). The results are consis tent with the hypothesis that thermal energy enhances heparin binding to tissues and that local application of a heparin film favorably modu lates arterial luminal responses to LBA, but not to BA, in this animal model. (C) 1994 Wiley-Liss, Inc.