Elastase is not sufficient to induce experimental abdominal aortic aneurysms

Purpose: Research investigating abdominal aortic aneurysms (AAAs) commonly uses a rat model dependent on aortic infusion of porcine pancreatic elastas e to initiate AAA formation. Unfortunately, the sizes of AAAs generated by this model have varied widely among published studies. This may reflect lot -to-lot variations in commercial elastase preparations. This study was unde rtaken to investigate the ability of different lots of elastase to induce A AAs and explain the variability identified. Methods: Four lots of elastase were evaluated in the standard rat AAA model . Saline solution was used as a control. Additional groups of rats were tre ated with higher concentrations of elastase with or without the macrophage activator thioglycollate medium. Aortic diameters were measured in all rats . Inflammation and elastin degradation was examined histologically. Elastas e activity and purity were evaluated for all lots. Results: Of the four lots tested, only one was able to consistently generat e AAAs at the standard dose (P < .05). Increasing the amount of elastase in fused produced AAAs in some ineffective lots. Infusion of thioglycollate me dium in combination with otherwise ineffective elastase produced AAAs (P =. 02). However, the elastase with the highest purity failed to generate AAAs, even at the highest dose tested or in combination with thyioglycollate med ium. Thioglycollate medium alone failed to result in AAA formation. All ela stase lots displayed elastolytic activity in vitro and produced elastin deg radation in vivo. Elastin degradation did not correlate with AAA size in el astase-treated rats (P = NS). Aneurysm size correlated with extent of infla mmation (P =.005). Conclusion: Induction of AAAs does not correlate with elastolytic activity. Infusion of pure elastase alone is not sufficient to induce AAA formation in spite of evidence of elastin degradation. Presumed inflammatory modifier s, which contaminate some elastase preparations, enhance AAA formation. Fut ure use of this rat model will need to take the variability of elastase pre parations into account with controls for each new elastase lot.