Restenosis following transluminal angioplasty in experimental atherosclerosis.

Percutaneous transluminal angioplasty has received considerable attention in the treatment of obstructive atherosclerotic lesions in humans. However, restenosis frequently occurs and has limited the long-term effectiveness of this procedure. To study restenosis, a model of atherosclerosis was developed in 16 New Zealand rabbits. Atherosclerosis was induced in one or both iliac vessels by balloon deendothelialization followed by a 2% cholesterol diet for 6 weeks. Angiographic lesions were demonstrable in all animals. Fourteen iliac vessels served as controls, and nine underwent successful angioplasty with an increase in luminal diameter from 1.0 +/- 0.2 to 1.9 +/- 0.4 mm (p less than 0.01). After 4 weeks on a high cholesterol diet, all animals had another angiogram, which documented significant progression of disease in only six of 14 control iliac vessels, but in all nine dilated vessels. The average decrease in luminal diameter was 0.2 +/- 0.3 mm for the control group compared with 1.6 +/- 0.5 mm for the dilated group (p less than 0.01). Histopathological correlates revealed further remodeling of at various stages of organization and recanalization. In summary, this study demonstrates that restenosis occurs following transluminal angioplasty and is significantly more frequent than the natural progression of disease in a rabbit model of atherosclerosis. The mechanism of this restenosis appears to be related to intraluminal thrombosis and acceleration of atherosclerosis. Evaluation of antiplatelet drugs in the prevention of restenosis seems warranted.

The mechanism of transluminal angioplasty: evidence for formation of aneurysms in experimental atherosclerosis.

Quantitative histologic examination (morphometric analysis) of pressure-perfused rabbit atherosclerotic arteries was used to determine whether compression of atheromatous material occurs with transluminal angioplasty. Experimental atherosclerosis was developed in both iliac arteries, with transluminal angioplasty performed on the left iliac while the right iliac served as a nondilated control. Angiography showed equal degrees of luminal narrowing before angioplasty (p = NS). Angioplasty reduced the left iliac narrowing in all animals studied. Morphometric analysis of histologic sections of the left and right iliac arteries disclosed significant differences in luminal and total vessel areas (p less than .05), whereas arterial wall (intima and media) areas were similar (p = NS). Dilated areas often demonstrated marked intimal splitting with dissection into the media. At higher magnification, loss of nuclear staining and dense layers of extracellular matrix consistent with stretching were frequently seen. It is concluded that the major mechanism of successful transluminal angioplasty is stretching of the vessel, resulting in localized aneurysm formation. Intimal splitting implies inelasticity of the neointima. No evidence of compression and remodeling of atheromatous material was disclosed in this study.

Transluminal angioplasty in experimental atherosclerosis. Analysis for embolization using an in vivo perfusion system.

We used polarized light microscopy and thin-layer chromatography to determine whether embolization of atherosclerotic material occurs after transluminal angioplasty. The experimental model consisted of an in vivo perfusion system of the atherosclerotic rabbit left iliac artery. Of eight rabbits that underwent successful angioplasty, four had angiographic evidence of dissection and three showed aneurysm formation. Histologic studies demonstrated fracture of the intimal plaque, dissection, and stretching of the noninvolved portion of the vessel. Perfusate analysis revealed no detectable cholesterol by thin-layer chromatography in six of eight rabbits. In two rabbits, a very small amount of cholesterol was measured, which was totally accounted for by hemorrhage into the perfusate rather than from cholesterol in the plaque. No evidence of arterial wall embolic debris could be detected by polarized light microscopy in seven rabbits, but lipid debris from the plaque was found in the perfusate of one rabbit that had excessive arterial trauma. We conclude that the major mechanism of successful transluminal angioplasty in this experimental model is intimal fracture combined with stretching of a noninvolved portion of the vessel. Furthermore, embolization of atheromatous lipid debris was an uncommon event related to arterial trauma during catheter placement rather than transluminal angioplasty itself.

Acute effects of transluminal angioplasty in three experimental models of atherosclerosis.

Transluminal angioplasty has shown promise as a nonoperative treatment of atherosclerotic obstruction. Despite its increasing clinical use and potential importance, little is known of its mechanism and acute effects. To evaluate transluminal angioplasty, three rabbit models of experimental atherosclerosis were developed: Group 1 (n = 20) = high cholesterol diet plus balloon de-endothelialization; Group 2A (n = 12) = high cholesterol diet plus an indwelling catheter; Group 2B (n = 10) = normal diet plus an indwelling catheter. After 6 weeks or 8 weeks, distinct angiographic and pathological lesions in the iliac artery were evident in all groups. Group 1 showed predominant foam cell lesions, while Group 2 showed eccentric mixed fibrous and foam cell or only fibrous lesions. Significant angiographic stenosis was present in 78% of the animals. Angioplasty of the highest grade iliac stenosis resulted in at least a 20% reduction in luminal diameter narrowing in 26 of 37 animals (70%). Histopathological examination 1 day following angioplasty in 17 animals showed two patterns. In Group 1 animals, neointimal fracture and dissection were evident, while in Group 2 animals thinning and stretching of the nonatherosclerotic portion of the vessel walls could be demonstrated. This study demonstrates that the New Zealand rabbit can be used to produce a spectrum of morphologically distinct atherosclerotic lesions that lend themselves to the study of transluminal angioplasty. The immediate consequences of angioplasty, which appear to depend upon the underlying histopathology and widening of the narrowed lumen, are frequently concurrent with intimal fracture, dissection, or thinning of the nonatherosclerotic portion of the vessel wall.