The External Aortic Wrapped Graft Restrain the Growth of the Ascending Aorta in a Large Animal Model: Functional, Molecular and Morphological Changes After Minimally Invasive Aortic Root Support: Six-month Follow-up

Abstract

Introduction: Elective external aortic root support is intended to prevent further aortic dilatation, to preserve the valve function, and secure the size and configuration of the aortic wall. The aim of this study was to determine the feasibility of conducting a minimally invasive external aortic root support in a growing porcine model and to evaluate functional, molecular and morphological changes in the structure of the reinforced aortic wall during six-month follow up. Methods: Nine animals were randomized into one control group (3 animals without aortic root support) and one treatment group (6 animals). In the treatment group the segment of prosthetic tube graft was trimmed and secured around of the ascending aorta (from the aortic annulus to the innominate artery) via a minimally invasive approach. Six months after implantation the wrapped aorta and surrounding tissues were removed. The fragments were collected from the different aortic areas for histologic and molecular studies. Morphometric analyzes were performed on electron transmission microscopy samples using image software system. We additionally performed an assessment of cardiac structures and valve function using transthoracic and epicardial aortic echocardiography and spectral Doppler modalities. For molecular evaluation of aortic fibrosis the transforming growth factor beta (TGFβ) pro-fibrotic signaling genes, Smad protein family and different types of collagen were examined by real-time polymerase chain reaction and western blotting. Results: All animals survived without any complications until planned euthanasia. The external wraps were well incorporated into the aortic adventitia. No graft migration, hematoma formation, medial necrosis or aortic erosion were observed. All animals had normal LV systolic and diastolic dimensions, shortening fractions and ejections fractions at baseline. At the 6-month follow-up we did not find significant changes in end-systolic and end-diastolic volume, LV ejection fraction, aortic and mitral valve functions. Aortic flow velocity in pre- and post-graft areas was similar (∼1.5 m/s). The expression of signaling components of TGFβ system and Smad family genes were not significantly up-regulated in the segments of external prosthetic wrapping. A significant increase was found in the ratio of the de novo to mature collagen by multispectral histological imaging. The abundance of muscle fibers and smooth muscle cells in the aortic media tended to decrease but was not significantly different between the groups. Despite the restrained of growth of the ascending aorta and aortic root, all animals showed normal growth pattern, including size and body weight. Conclusion: The implanted graft was embedded in the adventitia and not separable from the aortic wall. The external aortic wrapped material successfully restrained the growth of the ascending aorta in an animal model without affecting the normal growth pattern of the animal itself. Molecular and morphometric analysis revealed a moderate fibrotic reaction without significant inflammation. Disclosure: Nothing to disclose