THE ELASTASE INFUSION MODEL OF EXPERIMENTAL AORTIC-ANEURYSMS - SYNCHRONY OF INDUCTION OF ENDOGENOUS PROTEINASES WITH MATRIX DESTRUCTION ANDINFLAMMATORY CELL RESPONSE

Purpose: Perfusion of the isolated aorta of the rat with a saline solu tion containing pancreatic elastase induces an abdominal aortic aneury sm (AAA). An interesting feature of this model is the phenomenon of la tency, suggesting that additional steps beyond the initial injury are required for AAA formation. This study was performed to determine whet her the latency period for aortic dilation to aneurysmal proportions i s correlated with the appearance of proteinases of endogenous origin a nd the interval for infiltration of inflammatory cells. Methods: Twent y Wistar rat aortas were perfused with the test solution, and 20 with normal saline solution. Laparotomy was performed on days 1, 2, 3, and 6 for measurement and harvest of the aorta. Histochemical studies were performed to analyze changes in matrix proteins, and substrate gel en zymography was used to determine the appearance of endogenous proteina ses. Immunohistochemical studies were performed with monoclonal antibo dies to T cells (CD-4, -5, and -8), monocytes/macrophages (ED-2), B ce lls (LC-A), immunoglobulin G, and immunoglobulin M. Results: The exoge nously administered elastase was not detectable beyond day 2, but the aortic diameter did not progress to aneurysmal dimensions until the in terval between days 3 and 6. During the period from day 3 to day 6, mu ltiple endogenous matrix proteinases became detectable in the aortic t issue preparations. Immunohistochemical study revealed progressive inf iltration of the aorta with various subsets of inflammatory cells. Con clusion: The results suggest that the latency in AAA formation in this model corresponds with a complex sequence of biochemical and cellular events. The model provides an ''early window'' into these interesting early phases leading to aneurysm formation.