VASCULAR INJURY AND TIME COURSE OF SMOOTH-MUSCLE CELL-PROLIFERATION AFTER EXPERIMENTAL HOLMIUM LASER ANGIOPLASTY

Background. In vitro experiments have shown that holmium laser energy can effectively ablate even calcified plaque in human arterial vessels. Because high-energy densities from holmium lasers can easily be transmitted through quartz fibers, this solid-state laser has been suggested as an alternative intraluminal treatment of atherosclerotic plaque. Methods and Results. To develop an intimal plaque, 35 New Zealand White rabbits underwent electrical stimulation of their right carotid artery for 28 days. Subsequently, in 25 rabbits, holmium laser angioplasty (wavelength, 2.12 mum; pulse duration, 150 musec; energy density, 350 mJ/mm2) was performed. To study the morphological results, the vessels were excised after 7, 14, 28, and 42 days. Cross sections were analyzed in regard to laser-specific injury. Staining of alpha-actin was used to identify smooth muscle cells (SMCs). After bromodeoxyuridine labeling, the extent of proliferation (number of cells undergoing DNA synthesis) was determined by using a monoclonal antibody. Holmium laser ablation resulted in an initial decrease of the numbers of intimal cell layers in the early group (7 days after treatment: 5+/-1 cell layers with 76+/-39 mum; control: 13+/-3 cell layers with 144+/-44 mum). Quantification of SMCs undergoing DNA synthesis in the intima (control: 51+/-19 cells/mm2) showed a significant increase of labeled cells after 7 (216+/-74 cells/mm2, p=0.003) and 14 days (281+/-139 cells/mm, p=0.011). Integrity of the internal elastic lamina was disrupted in all animals after intervention. Seven and 14 days after treatment, a considerable reduction of medial cell nuclei was found in 10 of 12 animals. SMC proliferation in the medial layer was increased within the first 2 weeks after laser ablation (168+/-113 cells/mm2; control: 8+/-4 cells/mm2; p=0.023). Six weeks after holmium laser angioplasty, SMC proliferation had returned to control levels in the intima and remained increased in the medial layer. This proliferative response resulted in a significant increase of intimal thickening within 6 weeks after laser ablation (30+/-6 cell layers, 375 +/- 97 mum resp.; p =0.001 each). Conclusions. Holmium laser treatment leads to considerable vessel wall injury and results in SMC proliferation in the intimal and medial layer with a maximum of proliferative activity within the first 2 weeks. Subsequently, this results in considerable intimal and medial hyperplasia within 6 weeks after treatment.