A minimally invasive endovascular rabbit model for experimental induction of progressive myocardial hypertrophy

The purpose of this paper is to describe a novel minimally invasive endovascular model of progressive myocardial hypertrophy in rabbits as an experimental protocol of hypertrophic cardiomyopathy. Nine New Zealand White rabbits underwent transauricular aortic catheterization. Under fluoroscopy a bare metal stent was partially deployed in the descending thoracic aorta (balloon length/stent length=1/2) so as to produce a funnel-shaped thoracic stent. Another nine animals underwent a sham procedure without stent placement (control). Follow-up computed tomography imaging was performed to exclude aortic occlusion. Subjects were killed after 3 months and their hearts were harvested and weighed. Cardiac hypertrophy was assessed with the heart weight-to-body weight (HW/BW) ratio and post-mortem histology was performed. We also used immunohistochemical staining for myogenin to compare the thickness of the wall between the two groups. The stents were polymer embedded for histomorphometry. Expressions of vascular endothelial growth factor (VEGF) and pleiotrophin (PTN) were analyzed by western blot analysis of total protein heart extracts. Computerized image analysis of CD34 and VEGF immunoreactivity was used to quantify myocardial angiogenesis. After 3 months, cross-sectional microscopic analysis of the harvested aortas showed total stent occlusion of the distal underdeployed area and some evidence of thrombus formation at the transitional zone toward the fully deployed stent in all cases. There was a nearly +10% increase of the adjusted HW/BW ratio compared with controls (absolute ratio difference was 0.02±0.01%; P=0.02). VEGF and CD34 expression was significantly suppressed, but expression of PTN was significantly increased in case of myocardial hypertrophy (stent group). Cardiac hypertrophy was evidenced using immunohistochemical staining for myogenin by significantly increased cardiomyocyte cross-sectional area (+38.4%; P<0.0001) compared with the control animals. In conclusion, this minimally invasive novel technique of transauricular funnel-shaped stent insertion in the descending thoracic aorta may achieve progressive myocardial hypertrophy in rabbits.