Background: Small-animal models of arterial aneurysm have provided important insights concerning pathogenesis but do not permit evaluation of novel medical devices where an aortic diameter similar to human is deemed necessary. Existing large-animal models, e.g. balloon-dilatation, periaortic restriction, or surgical patch to enlarge the lumen, are of limited use for determining the effect of novel technologies on cellular mechanisms of aneurysmal dilatation. We present a novel, laparoscopy-based, mechanism-oriented pig model of AAA.
Methods: The infrarenal aorta of seven male arlan pigs (33-37kg) was exposed laparoscopically. CaCl2(0.5M) was applied to the central third by saturating cotton gauze placed periarterially(20min.). Angiotensin-II was delivered by osmotic minipump (Alzet-2ML4) inserted retroperitoneally or into the abdominal cavity. Instruments were then withdrawn and access ports closed. The diet of 3 was supplemented with 1%-cholesterol and 20%-beef tallow beginning 1 month prior to induction of aneurysm. The animals were imaged serially by ultrasonography or CT until sacrifice at 4-6 weeks and the aortas excised for histopathology.
Results: Correlation of H&E- with Von Kossa-stained sections showed preferential deposition of calcium within the elastic lamellae of the intima and media. This was confirmed by electron-dispersive spectroscopy. The calcium-elastic tissue complex was the focus of inflammatory-cell infiltration. Disruption of the medial lamellar units was associated with focal replacement of SMC by extracellular matrix and variable degrees of intramural hemorrhage. Aortic-wall expansion occurred in all, but luminal expansion (>50% over baseline) occurred only in the 3 fed a hyperlipidemic diet (diet-vs-no diet: 3 of 3-vs-0 of 4, p=0.029 by Fisher Exact). Two of the 3 hyperlipidemic pigs had aortic rupture.
Conclusion: This study points to an important contributory role for diet in luminal expansion of aortas with calcific deposits, and provides strong support for the relevance of this laparoscopy-based model to the pathobiology of human AAA and for testing novel mechanism-based treatments.
