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This study was designed to assess the potential relationship between the late loss of angiographic luminal diameter and biochemical abnormalities of arterial wall collagen in rabbits subjected to angioplasty, and to test the hypothesis that beta-aminopropionitrile (beta APN), an inhibitor of lysyl oxidase, would inhibit such changes when administered orally for 1 mo after angioplasty. Endovascular injury was induced in rabbit iliac arteries by ipsilateral balloon angioplasty (BA) and by contralateral balloon angioplasty accompanied by exposure to continuous wave neodymium: yttrium aluminum garnet laser radiation (LBA). Computer measurement of angiographic luminal diameter demonstrated significant vessel narrowing at 1 and 6 mo after both procedures. By quantitative histology, the majority of the 1-mo loss in angiographic diameter could not be attributed to neointimal thickening. Analysis of collagen cross-linking by HPLC in collagen obtained from the LBA-injured segments of the arteries 1 mo after angioplasty revealed a significant increase, relative to values from uninjured arteries (P < 0.05), in the difunctional cross-link dihydroxylysinonorleucine (DHLNL). 6 mo after angioplasty, the content of hydroxypyridinium, the trifunctional maturational product of DHLNL, was significantly elevated in both BA- and LBA-treated arteries compared with values from uninjured arteries (P < 0.05). In animals administered beta APN, luminal narrowing at 1 mo, compared with controls, was attenuated (P < 0.01) and DHLNL content was decreased (P < 0.05) in arteries subjected to LBA, but not in arteries subjected to BA. The results suggest that lathyrogenic agents may be efficacious in favorably modulating LBA-induced alterations in vessel diameter and mural connective tissue.

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.

Laser Balloon Angioplasty (LBA) is a technique that may improve the results of balloon angioplasty by thermally sealing arterial dissections and reducing elastic recoil. To define the relationship between laser-exposure duration and the strength of thermal welds made between separated layers of arterial wall, 360 1-cm discs of human postmortem aorta were lased for six different exposure intervals at three different temperature ranges, comparing shear strength of thermal welds in the different groups. Twenty discs were lased to achieve plateau adventitial temperatures of 95 degrees C-104 degrees C (group A), 105 degrees C-114 degrees C (group B), or 115 degrees C-124 degrees C (group C) at each of the exposure periods (5, 10, 15, 20, 25, and 30 sec). A 400-micron fiberoptic coupled to a 1.06 micron continuous wave neodymium:YAG laser was placed perpendicularly 8 mm above the luminal surface of each disc, which had been split midway between the intimal and adventitial surface and reapposed. Mean laser energy ranged 78-378 J delivered in a decremental stepwise fashion to achieve quickly and maintain the target plateau tissue temperature. Mean weld strength increased in relation to both achieved tissue temperature and laser-exposure duration, with at least 10 sec necessary, at temperatures greater than 95 degrees C, for reliable thermal welding. Laser exposure for greater than 20 sec provided no statistical increment in weld strength. In the anticipated clinical performance of LBA, these data suggest that when thermal fusion of disrupted arterial tissues is desired, a laser-exposure duration of 10-20 sec is optimal.

Thermal fusion of intimal plaque with the arterial wall during coronary balloon angioplasty may significantly reduce the incidence of abrupt closure and may reduce the occurrence of delayed restenosis by improvement of luminal size and shape. Although Nd:YAG laser energy has been shown to be effective in the thermal fusion of plaque-arterial wall separations in vitro, the most efficient manner of energy delivery for rapid achievement of therapeutically useful equilibrium tissue temperature during laser exposure has not been defined. A comparison of weld strength achieved was therefore made between two formats of laser delivery: constant power vs. decremental power with an initial high dose followed by the minimal serial decrements necessary to maintain tissue temperature constant for 15 seconds. One hundred sixty-six tissue discs of human postmortem aorta of 11 mm diameter were studied. Intimal plaque was separated from the media, the two layers were juxtaposed, a force of 4 pounds was applied, and a fiberoptic-delivered laser beam was directed perpendicular to the tissue over a 3-mm-diameter nominal spot size. Weld strength was measured as the shear force required to separate completely the two tissue layers. The mean weld strength (75 g) achieved by use of the decremental power format was significantly higher (P less than .01) than the mean strength (32 g and 56 g) achieved by using constant power for 20 and 30 seconds, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Restenosis after percutaneous transluminal coronary angioplasty may result primarily from the combination of a thrombogenic surface and local flow separation produced by disruption of the arterial wall and lumen. Elastic recoil and, perhaps, cellular proliferation further contribute to luminal compromise after percutaneous transluminal coronary angioplasty. Laser balloon angioplasty, performed during the final inflation of an otherwise conventional balloon angioplasty procedure, uses the coagulative properties of Nd:YAG laser radiation to weld together disrupted tissue elements thermally, to reduce elastic recoil and to destroy viable arterial tissue. Studies in human postmortem atheromatous arteries and in animal models in vivo indicate that laser balloon angioplasty, by creating a lumen that approximates the size and smooth cylindrical shape of the balloon, should be effective in the treatment of important causes of restenosis.

Reduction of vascular recoil is an important goal of laser balloon angioplasty (LBA), wherein Nd:YAG laser radiation is delivered radially during balloon inflation. To define the acute and chronic effects of LBA on the normal arterial lumen in comparison with those of balloon angioplasty (BA), 36 New Zealand White male rabbits (3-4 kg) were subjected to LBA of an external iliac artery and to BA of the contralateral artery with two 1-minute balloon inflations. During LBA, which was performed during the second balloon inflation, either 300 (n = 26) or 176 (n = 10) J were delivered to achieve high and moderate laser doses, respectively, in different LBA groups. Angiography was performed pre- and post-LBA/BA and subsequently at intervals of either 1, 2, 7, 28, 48, or 223 days. Automated analysis of digitized images was used to measure lumen diameter. No instance of perforation or thrombosis occurred. LBA-treated arteries acutely showed an increase in mean diameter over baseline (+ .5 mm, P less than .01) and that of BA-treated arteries (+ .4 mm, P less than .01). While arteries treated with the high laser dose showed a loss of the initial gain in lumen diameter by 1 month, caused by both extravascular fibrosis of the thinwalled (less than 0.1 mm) artery and mild neointimal proliferation which were not reduced by daily administration of aspirin in seven rabbits, arteries treated with the moderate laser dose retained the increment in mean diameter at 1 month over that of BA-treated arteries (+ .5 mm, P less than .05). Thus, unlike BA, LBA increases luminal diameter acutely and, at a moderate laser dose, chronically.

Dehiscence of portions of atheromatous plaques fractured during percutaneous transluminal coronary angioplasty may contribute to both abrupt reclosure and gradual restenosis. Laser balloon angioplasty has been shown to be effective in welding human plaque-arterial wall separations in vitro by heating tissues with a Nd:YAG laser during balloon inflation. To define the potentially useful therapeutic range of tissue temperature required to achieve thermal welds, 220 1-cm diameter discs of human postmortem atheromatous aortic tissue, the intimal plaque of which had been separated from the media, were exposed to 3-25 watts of Nd:YAG laser radiation delivered over a 12-mm2 nominal spot size for 20 seconds via a 400-micron core optical fiber. As measured with a thermistor, adventitial temperature reflected the temperature at the plaque-media junction to within 10 degrees C. The degree of tissue temperature elevation was related to delivered energy, while effective tissue penetration increased to maximum depth of 3 mm at the highest power density. Strength of tissue welds was defined as the force required to shear opposing layers of welded segments. Adventitial tissue temperatures below 80 degrees C were not associated with appreciable welds, while equilibrium temperatures between 95 degrees C and 140 degrees C were consistently associated with effective mean weld strengths, which increased linearly from 25 to 110 g, respectively. Temperatures greater than 150 degrees C were associated with rapid tissue dehydration and charring. These data suggest that the therapeutic range of tissue temperature that provides effective thermal fusion of intima-media separations is broad and that the depth and degree of thermal coagulation can be controlled by manipulation of laser energy delivery.