Abstract
Although the mechanisms of the clinical benefits of transmyocardial laser revascularization (TMLR) are considered to be angiogenesis with increased perfusion, denervation and placebo effect, it is unknown whether laser energy is a prerequisite in obtaining these beneficial effects. The present study investigated whether it is possible to create transmyocardial channels and induce angiogenesis by ultrasound. Myocardium was penetrated with an ultrasonically activated surgical blade by advancing the blade tip perpendicularly to the left ventricular free wall of the beating heart of 6 mongrel dogs. The power of ultrasound was set at either the lowest or highest of the system. The animals were killed 30 min (acute; n=3) and 2 weeks (chronic; n=3) after channel creation. Holmium:YAG laser, which is currently used for clinical TMLR, was used to create myocardial channels in 4 other dogs, which were also killed 30 min (n=2) and 2 weeks (n=2) after channel creation. The areas of acute channel core, acute thermal damage and chronic fibrosis were compared between the laser and ultrasound channels by Masson's trichrome stain. Factor VIII and proliferating cell nuclear antigen (PCNA) immunostaining were carried out on the samples obtained from chronic animals. The density of vessels and that of proliferating vascular endothelial cells and vascular smooth muscle cells around the channels were measured. The area of acute core was larger in the lowest and highest outputs of ultrasound than in laser channels (0.78+/-0.09, 1.0+/-0.12 vs 0.38+/-0.04 mm2; p<0.01). The area of acute damage in both laser and the highest output of ultrasound channels was greater than in the channels produced by the lowest output of ultrasound (4.43+/-0.28, 4.63+/-0.44 vs 2.90+/-0.29 mm2; p<0.01). The ratio of acute damage area to acute core area was greater in laser channels than in either type of ultrasound channel (16.86+/-1.66 vs 6.04+/-0.67, 7.86+/-1.07; p<0.01) and the area of chronic fibrosis was greater (3.23+/-0.20 vs 1.59+/-0.18, 2.24+/-0.20 mm2; p<0.01). Factor VIII and PCNA immunostaining revealed new vessels not only inside the areas of chronic fibrosis, but also in the surrounding myocardium, in both laser and ultrasound channels. Ultrasound created transmyocardial channels histologically similar to laser channels and angiogenesis was induced in the normal myocardium surrounding ultrasound channels.
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