PURPOSE: To develop a small animal model of controlled aortic intimal injury with ultrasound (US) imaging guidance. MATERIALS AND METHODS: Via carotid artery cutdown, a custom-made microcatheter/angled metal device system was advanced to damage the intima of the ascending aortas of 20 Sprague-Dawley rats and 10 JCR atherosclerotic rats. This minimally invasive endovascular procedure was monitored by a clinical US imaging system. Injured aortas were harvested for histologic confirmation via a grading system: grade I, intima injury; grade II, injury to media; and grade III, injury through the entire aortic wall. Neointimal reactions at the injury site were compared by calculating the ratio of intimal to medial thickness among different animal groups at various survival times (week 1, weeks 2-3, and weeks 4-7). RESULTS: Clear visualization of the architecture of the heart and great vessels and the exact location of the angled metal device by US imaging ensured consistent intimal damage of the aorta. Histopathologic analysis confirmed that most of the aortic injures were classified as grade I. There was no significant difference between the two rat groups. Analysis of pathophysiologic reactions at the injury sites revealed increased thickening of neointimal hyperplasia as animal survival times extended from week 1 to weeks 4-7 after the aortic interventions. CONCLUSIONS: This study demonstrates the feasibility of clinical US imaging to precisely guide the creation of controlled aortic intimal injury in rats, which may become a useful tool to facilitate research involving the prevention and treatment of atherosclerotic cardiovascular disease.
PURPOSE: To develop a small animal model of controlled aortic intimal injury with ultrasound (US) imaging guidance. MATERIALS AND METHODS: Via carotid artery cutdown, a custom-made microcatheter/angled metal device system was advanced to damage the intima of the ascending aortas of 20 Sprague-Dawley rats and 10 JCR atheroscleroticrats. This minimally invasive endovascular procedure was monitored by a clinical US imaging system. Injured aortas were harvested for histologic confirmation via a grading system: grade I, intima injury; grade II, injury to media; and grade III, injury through the entire aortic wall. Neointimal reactions at the injury site were compared by calculating the ratio of intimal to medial thickness among different animal groups at various survival times (week 1, weeks 2-3, and weeks 4-7). RESULTS: Clear visualization of the architecture of the heart and great vessels and the exact location of the angled metal device by US imaging ensured consistent intimal damage of the aorta. Histopathologic analysis confirmed that most of the aortic injures were classified as grade I. There was no significant difference between the two rat groups. Analysis of pathophysiologic reactions at the injury sites revealed increased thickening of neointimal hyperplasia as animal survival times extended from week 1 to weeks 4-7 after the aortic interventions. CONCLUSIONS: This study demonstrates the feasibility of clinical US imaging to precisely guide the creation of controlled aortic intimal injury in rats, which may become a useful tool to facilitate research involving the prevention and treatment of atherosclerotic cardiovascular disease.
Authors: Jan H von der Thüsen; Bart J M van Vlijmen; Rob C Hoeben; Mark M Kockx; Louis M Havekes; Theo J C van Berkel; Erik A L Biessen Journal: Circulation Date: 2002-04-30 Impact factor: 29.690