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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
Author(s) -
Spears J. Richard,
Yellayi Subrahmanya S.,
Makkar Raj,
Nallamothu Nasaraiah,
Rizvi Mohammad A. D.,
Sheriff Mohammad U.,
Khetpal Vikram,
Zhan Hong,
Jang Jie,
Kundu Sourav K.,
Zaidan Jonathan T.,
McMath Linda P.,
Wang Tao,
Mammen Eberhard F.,
Khan Muhammad A.,
Sathavorn Charn S.,
Fromm Barbara
Publication year - 1994
Publication title -
lasers in surgery and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.888
H-Index - 112
eISSN - 1096-9101
pISSN - 0196-8092
DOI - 10.1002/lsm.1900140406
Subject(s) - heparin , angioplasty , in vivo , aorta , medicine , anticoagulant , thrombus , in vitro , fibrin , pharmacology , pathology , chemistry , surgery , cardiology , immunology , biology , biochemistry , microbiology and biotechnology
Experimentally, heparin inhibits mechanisms that promote fibrosis, neointimal cellular proliferation, and thombin 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 3 H‐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. 3 H‐heparin binding to clot, whole blood particulates, and washed erythrocytes was markedly enhanced by exposure to temperatures > 70°C. Thermal exposure (80°C × 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°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. © 1994 Wiley‐Liss, Inc.