Shortened Elastase Infusion Time in the Elastase-Induced Rat Aneurysm Model

Yamaguchi, Toshiyuki; Yokokawa, Masayasu; Suzuki, Mamoru; Higashide, Shinji; Katoh, Yoshimasa; Sugiyama, Shigeki; Misaki, Takuro

doi:10.1006/jsre.1999.5622

Cited by 10 publications

(9 citation statements)

References 14 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some investigators have recently pointed out that the 2-hour infusion time in this model has some drawbacks, including high mortality related to the long elastase infusion time and hind limb ischemia caused by the cross-clamping period of the infrarenal aorta. 13,21 We also recognized the difficulty in keeping a constant pressure for the elastase infusion for such a long time. A decrease in the elastase infusion time would be expected to reduce those drawbacks, and Yamaguchi et al 14 and Sinha et al 15,16 have recently shown successful rat AAA models with a 30-minute elastase infusion.…”

Section: Discussionmentioning

confidence: 97%

A novel rat model of abdominal aortic aneurysm using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure

Tanaka

Hasegawa

Chen

et al. 2009

Journal of Vascular Surgery

View full text Add to dashboard Cite

Objective: An ideal animal model of abdominal aortic aneurysm (AAA) is of great importance for clarifying unknown complex mechanisms of the pathogenesis. We introduce a new, simple technique to create reliable AAAs that simulate human aneurysms. Methods: Experimental models of AAAs were created in 71 rats by means of a 20-minute application of intraluminal elastase (30 U) and extraluminal calcium chloride (0.5M) in the 1-cm segment of infrarenal abdominal aorta (group EC, n ‫؍‬ 26). A single application of elastase (group E, n ‫؍‬ 24) or calcium chloride (group C, n ‫؍‬ 21) was used as control. The treated aorta in each group was measured under physiologic conditions and harvested at 1 and 4 weeks. Successful AAA formation was defined as a dilation ratio >50%. Inflammatory response, elastolytic activity, and histology in the treated aorta were evaluated among the three groups. Results: The surgical procedure in each group was similarly completed for approximate 30 minutes and performed without any technical failure or operative death. At 4 weeks, the dilation ratio and wall thickness were 94.8% ؎ 9.9% and 125.4 ؎ 5.6 m in group EC, 43.3% ؎ 6.3% and 149.6 ؎ 6.5 m in group E, and 10.9% ؎ 4.2% and 152.9 ؎ 7.2 m in group C. The success rate of AAA formation in group EC (92.7%) was significantly higher than that in group E (25.0%) and group C (0.0%). Less elastin content in the aortic wall was observed in group EC. At 1 week, tumor necrosis factor-␣ and interleukin-1␤ messenger RNA (mRNA) expressions were significantly upregulated, and CD3؉ and CD11b؉ cells were significantly infiltrated into the treated aorta of group EC, compared with groups E or C. Gelatinolytic activities and mRNA expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were also significantly activated in group EC. Conclusion: The rat AAA model using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure is simple and easy to perform and is highly reliable and reproducible to create a saccular aneurysm similar to human AAAs. This model could be more useful to clarify AAA pathogenesis, mechanisms, and treatment interventions in experimental researches. ( J Vasc Surg 2009;50:1423-32.)Clinical Relevance: Abdominal aortic aneurysm (AAA) typically has a silent nature, and its rupture has high morbidity and mortality. There are currently no therapeutic approaches to prevent AAA, and complete mechanisms of AAA formation are still poorly understood. We developed a novel rat AAA model using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure. This model is simple and easy to perform and is highly reliable and reproducible to create a saccular aneurysm. It could become a powerful tool not only to elucidate etiopathogenetic mechanisms of AAA formation but also to explore new diagnostic and therapeutic possibilities.

show abstract

Section: Discussionmentioning

confidence: 97%

A novel rat model of abdominal aortic aneurysm using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure

Tanaka

Hasegawa

Chen

et al. 2009

Journal of Vascular Surgery

View full text Add to dashboard Cite

show abstract

“…10,12,13,[15][16][17][18][19][21][22][23][24] In this study, we used a modification of the model that we recently described. 25 An inflammatory response is a critical step in this model. 11,14 In fact, previous investigators have demonstrated that aortic dilatation was attenuated by systemic treatment with leukocyte-depleting monoclonal antibodies, 16 anti-inflammatory drugs, 18,21 and immunosuppressants 17 using this model.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] These inflammatory cells include neutrophils, monocyte-macrophages, and lymphocytes. 11,13,14,17,18 The interactions of these cells with one another modify their functions at the sites of inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…Surgery was performed in all animals to facilitate elastase infusion of the infrarenal aorta with porcine pancreatic elastase (PPE) as described in our previous study. 25 Briefly, 24 male Sprague-Dawley rats weighing about 300 g were anesthetized with 6% sodium pentobarbital, 0.1 ml/100 g body weight (Abbott Laboratories, North Chicago, IL, USA) and a laparotomy was performed via a midline abdominal wall incision under sterile conditions. A 0.5-cm segment of infrarenal abdominal aorta was dissected free from the inferior vena cava, and the collateral arteries were ligated or clamped.…”

Section: Animal Modelmentioning

confidence: 99%

See 1 more Smart Citation

The Effect of Immunosuppression on Aortic Dilatation in a Rat Aneurysm Model

et al. 2000

Self Cite

View full text Add to dashboard Cite

This study was conducted to investigate whether systemic immunosuppression attenuated aortic dilatation in a rat aneurysm model. Sprague-Dawley rats were subjected to elastase infusion of the infrarenal aorta and divided into two groups of 12 rats each. The immunosuppression group (group 1) was given subcutaneous injections of cyclosporine A (5 mg/kg per day), azathioprine (2 mg/kg per day), and methylprednisolone (2 mg/kg per day) from the operative day until postoperative day (POD) 6. An additional subcutaneus injection of cyclophosphamide 30 mg/kg was also given on the operative day. The control group (group 2) was given subcutaneous injections of saline. Relaparotomy was performed on POD 7. After measurement of the aortic diameter, aortography and ultrasonography were performed in three rats from each group, following which the aortas were excised for histologic examination. The aortic diameter was significantly smaller in group 1 (2.58 +/- 0.37 mm) than in group 2 (6.21 +/- 1.74 mm) (P < 0.01) and the aortic lumen was slightly dilated in group 1, whereas it was spherically dilated in group 2. Total loss of elastic tissue was seen in both groups. Inflammatory cell infiltration and collagen fiber fragmentation were noted in group 2, whereas very little inflammatory cell infiltration and well-preserved collagen fibers were seen in group 1. These findings showed that immunosuppression attenuates aortic dilatation, partly by preserving the collagen fibers, in this rat aneurysm model.

show abstract

“…We recently reported a modified elastase-induced rat aneurysm model. 16 In developing our model, we noticed that the elastin fibers did not stain immediately after elastase infusion despite the absence of inflammatory cell infiltration. Therefore, we questioned the hypothesis that elastin fibers are not degenerated by infused elastase, but instead mainly by endogenous proteinases.…”

Section: Discussionmentioning

confidence: 97%

The time course of elastin fiber degeneration in a rat aneurysm model

et al. 2000

Self Cite

View full text Add to dashboard Cite

Previous findings vary regarding the timing and cause of elastin fiber degeneration in the elastase-induced rat abdominal aortic aneurysm model. We examined the timing and cause of elastin fiber degeneration after elastase infusion using two different elastase infusion times. Twenty-four Sprague-Dawley rats were divided into two groups. The infrarenal abdominal aorta was infused with 15 U of elastase for 15 min (n = 12, 15-min infusion group) or 30 min (n = 12, 30-min infusion group). In each group, three rats were killed immediately and 1, 3, and 7 days after infusion, and then the aortas were excised for a histologic examination. Elastin fibers did not stain, even immediately after elastase infusion, in the 30-min infusion group. The degeneration of elastin fibers did not progress in the 15-min infusion group during the period of observation. Inflammatory cells infiltrated mainly to the adventitia near regions where the degeneration of elastin fibers spread totally through the aortic media. Elastin fibers degenerate immediately after elastase infusion and thus seem to degenerate not due to endogenous proteinases that are produced by the infiltrating cells, but due to the exogenously infused elastase itself. Inflammatory cell infiltration was thus found to be a result of the degeneration of elastin fibers in this model.

show abstract

Shortened Elastase Infusion Time in the Elastase-Induced Rat Aneurysm Model

Cited by 10 publications

References 14 publications

A novel rat model of abdominal aortic aneurysm using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure

A novel rat model of abdominal aortic aneurysm using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure

The Effect of Immunosuppression on Aortic Dilatation in a Rat Aneurysm Model

The time course of elastin fiber degeneration in a rat aneurysm model

Contact Info

Product

Resources

About