title: 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.
abstract: Experimentally, heparin inhibits mechanisms that promote fibrosis, neointimal cellular proliferation, and thrombin bound to fibrin at the surface of intraluminal thrombus, but only in relatively high concentrations. A preliminary hypothesis was tested and confirmed in vitro that initial binding of 3H-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 binding of the drug. 3H-heparin binding to clot, whole blood particulates, and washed erythrocytes was markedly enhanced by exposure to temperatures > 70 degrees C. Thermal exposure (80 degrees C x 40 s) also enhanced 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 new method was developed for local application of a heparin film that provides 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 computer image analysis) in response to conventional balloon angioplasty (BA) and laser balloon angioplasty (LBA) was the same (P > 0.05). Local application of a heparin film (3,000 units at a concentration > 100,000 units/g), however, reduced the mean % loss in diameter 1 month after LBA (12%), but not after BA (29%), compared to arteries subjected to angioplasty without local heparin (P < .05). The results are consistent with the hypothesis that thermal energy enhances heparin binding to tissues and that local application of a heparin film favorably modulates arterial luminal responses to LBA, but not to BA, in this animal model.
authors.affiliation: Department of Medicine, Harper Hospital, Detroit, Michigan.
authors.forename: J R
authors.initials: JR
authors.lastname: Spears
authors.forename: S S
authors.initials: SS
authors.lastname: Yellayi
authors.forename: R
authors.initials: R
authors.lastname: Makkar
authors.forename: N
authors.initials: N
authors.lastname: Nallamothu
authors.forename: M A
authors.initials: MA
authors.lastname: Rizvi
authors.forename: M U
authors.initials: MU
authors.lastname: Sheriff
authors.forename: V
authors.initials: V
authors.lastname: Khetpal
authors.forename: H
authors.initials: H
authors.lastname: Zhan
authors.forename: J
authors.initials: J
authors.lastname: Jang
authors.forename: S K
authors.initials: SK
authors.lastname: Kundu
mesh_terms: D000800:Angioplasty, Balloon; D017222:Angioplasty, Balloon, Laser-Assisted; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001158:Arteries / Q000378:metabolism*; D001161:Arteriosclerosis / Q000378:metabolism; D001777:Blood Coagulation; D004910:Erythrocyte Membrane / Q000378:metabolism; D006493:Heparin / Q000008:administration & dosage / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D066298:In Vitro Techniques; D011817:Rabbits; D013552:Swine; D013927:Thrombosis / Q000209:etiology
chemical_list: D006493:Heparin