Simvastatin suppresses experimental aortic aneurysm expansion

OBJECTIVE: Abdominal aortic aneurysm (AAA) formation is a result of inflammation and extracellular matrix (ECM) remodeling mediated by matrix metalloproteinases (MMPs). Hydroxymethylglutaryl-coenzyme A inhibitors (statins), although clinically used as lipid-lowering agents, have also been demonstrated to have anti-inflammatory effects. This study was designed to determine whether the hydroxymethylglutaryl-coenzyme A inhibitor simvastatin suppresses aneurysm formation in an elastase-induced rat AAA model. METHODS: Aneurysms were created in adult male Wistar rats by infusion of elastase into isolated infrarenal aortic segments. The rats were randomized to receive either simvastatin (n = 17) or placebo (n = 17) by gastric lavage daily starting the day before surgery. The rats were euthanized and the infrarenal aortas harvested on postoperative day 7. Aortic diameters were measured before infusion, immediately after infusion, and at the time of harvesting. Protein expression was measured by immunoblot analysis. Gene expression profiling using Affymetrix U34A rat genome chips was performed to identify changes in gene expression caused by simvastatin treatment. RESULTS: Mean aneurysm diameter was significantly less in the simvastatin treatment group compared with controls (3.4 +/- 0.08 mm vs 4.3 +/- 0.19 mm; P = .0001). MMP-9 and nuclear factor-kappaB protein levels were decreased in the aortas of simvastatin-treated animals. Gene microarray analysis revealed 315 genes with statistically significant changes in expression (P < .05) in the simvastatin group. Genes related to inflammation, ECM remodeling, and oxidative stress function were downregulated. These included genes for interleukin 1, interleukin 4, inducible nitric oxide synthase, P-selectin, platelet-derived growth factor alpha, tumor necrosis factor, and several chemokines. CONCLUSIONS: Simvastatin significantly suppresses experimental aneurysm expansion and reduces protein levels of MMP-9 and nuclear factor-kappaB. Gene array analysis provides evidence that several mediators of inflammation, matrix remodeling, and oxidative stress are downregulated by simvastatin treatment. This suggests that simvastatin inhibits AAA formation by blocking the expression of certain proinflammatory genes. Simvastatin may be useful as an adjuvant therapy to suppress the growth of small aneurysms.     

MF-tricyclic inhibits growth of experimental abdominal aortic aneurysms

BACKGROUND: Experimental abdominal aortic aneurysm (AAA) development can be pharmacologically suppressed by inhibiting matrix metalloproteinase-9 (MMP-9). Cyclooxygenase-2 (COX-2) inhibitors are potent anti-inflammatory agents that have been demonstrated to inhibit experimental aneurysm development. We hypothesized that treatment with MF-tricyclic, a selective COX-2 inhibitor, incorporated into rodent chow would inhibit aneurysm development in a rat AAA model. METHODS: Twelve male Sprague Dawley rats underwent induction of experimental AAA using intra-aortic porcine elastase infusion. Six rats received control feed, and six received MF-tricyclic rodent chow for a period of 14 days. Aortic diameters were measured pre- and postinfusion as well as at harvest. Aortic tissue samples were evaluated by real-time polymerase chain reaction (RT-PCR) for MMP-9, by immunohistochemistry for elastin. RESULTS: Elastase infusion produced AAA in all untreated rats. At 14 days MF-tricyclic-treated rats had significantly reduced aortic diameter (1.9 +/- 0.1 mm versus 2.4 +/- 0.0 mm, P = 0.00001). Percent increase in aortic diameter was also significantly less in animals receiving MF-tricyclic (65.7 +/- 8.5% versus 132.3 +/- 7.3%, P = 0.0001). RT-PCR demonstrated a decrease in the mean expression of MMP-9 in the treated animals (0.414 ng of RNA versus 1.114 ng of RNA) (P = 0.07). Sections stained for elastin demonstrated preserved elastin integrity in MF-tricyclic treated aortas. CONCLUSIONS: COX-2 inhibition helps to retard the growth of experimental AAAs possibly through inhibition of MMP-9. Experimentally treated animals demonstrated smaller aortic diameters and lower levels of tissue MMP-9 when compared to untreated animals. Selective COX-2 inhibition may offer an additional method to pharmacologically inhibit AAAs.     

Matrix metalloproteinase expressions in arteriosclerotic aneurysmal disease

Medial degeneration of extracellular matrix (ECM) proteins in the wall of abdominal aortas results in smooth muscle cell destruction, a loss of architectural integrity, and abdominal aortic aneurysm (AAA) formation. It has been theorized that an imbalance between proteinases and their naturally occurring inhibitors is the cause of these observed histologic abnormalities. Therefore, the purpose of this investigation was to determine if differences in the matrix metalloproteinase (MMP) -2 and -9, tissue inhibitor of metalloproteinase-1 (TIMP-1), tissue-type plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA) protein and activity levels existed between infrarenal AAA and normal abdominal aortic tissue specimens. Between November 1995 and January 1997, 10 patients undergoing elective infrarenal AAA repair had a portion of their aneurysm walls snap frozen in liquid nitrogen and processed for subsequent western blot or zymographic analysis. Tissue specimens from 6 normal abdominal aortas obtained from fresh cadaver specimens were similarly processed and served as controls. Protein levels for MMP-2, MMP-9, TIMP-1, uPA, and tPA were analyzed by western blotting. The degree of MMP-2 and MMP-9 gelatinolytic activity was analyzed by zymography. Detection and immunolocalization for MMP-2, MMP-9 and CD68 was performed on tissue sections of AAA and normal infrarenal abdominal aortas fixed in 10% formalin. MMP-9 and tPA protein levels were increased in AAAs compared to controls by western blotting. However, uPA levels were slightly increased in controls. No differences in TIMP-1 protein levels were identified. Similarly, zymography demonstrated increased MMP-2 and MMP-9 gelatinolytic activity in AAAs compared to controls (p < or = 0.05). CD68-positive cells (macrophages) in the adventitia and media demonstrated immunoreactivity to MMP-9. This investigation demonstrated increased MMP-9 proteinase activity and tPA protein levels in the walls of AAAs, as well as inflammatory leukocyte invasion of the adventitia and media compared to controls. These data suggest that leukocyte-derived MMP-9 is associated with aortic wall degeneration and aneurysm formation. Furthermore, activation of MMP-9 may be caused by increased tPA levels in the walls of AAAs.     

Abdominal aortic aneurysms are associated with altered matrix proteins of the nonaneurysmal aortic segments

Purpose: Abdominal aortic aneurysms (AAA) are associated with diffuse arteriomegaly and peripheral aneurysms, suggesting a generalized process. Elastin and collagen are the key structural proteins of the aorta, and their relative content is markedly altered in tissue from AAA. Our purpose was to investigate elastin and collagen content in the proximal, nonaneurysmal segments of aortas with infrarenal AAA.Methods: After extraction of lipid, calcium, and soluble proteins, hydroxyproline (collagen) and desmosine-isodesmosine (elastin) contents were determined by high-performance liquid chromatography in the ascending and descending thoracic, supraceliac, and suprarenal aorta. By repeated measures of analysis of covariance, collagen was found to be increased throughout the aorta in AAA as compared with normal aorta or aorta with atherosclerotic occlusive disease. This difference remained significant when adjustments were made for group differences in age and degree of atherosclerosis. This increase in collagen content results in a dilutional decrease in elastin concentration. These data demonstrate that the same matrix protein alterations found in AAA tissue occur throughout the aorta, differing only in magnitude in the aneurysmal and nonaneurysmal segments. These data suggest that aneurysm formation may relate to alterations in the regulation of elastin and collagen. (J VASC SURG 1994;19:797-803.)     

Impact of endovascular repair on open aortic aneurysm surgical training.

PURPOSE: The purpose of this study was to determine the impact of an endovascular stent-graft program on vascular training in open aortic aneurysm surgery. METHODS: The institutional and vascular surgery fellow experience in aortic aneurysm repair during a 6-year period was reviewed. The 3-year period before introduction of endovascular repair was compared with the 3-year period after introduction of endovascular repair. All patients undergoing abdominal aortic aneurysm (AAA) or thoracoabdominal aortic aneurysm repairs were entered prospectively into a vascular registry and retrospectively analyzed to evaluate the changing patterns in aortic aneurysm treatment and surgical training. RESULTS: Between July 1994 and June 2000, a total of 588 patients with AAA or thoracoabdominal aneurysms were treated at Stanford University Medical Center. There were 296 (50%) open infrarenal AAA repairs, 87 (15%) suprarenal AAA repairs, 47 (8%) thoracoabdominal aneurysm repairs, and 153 (26%) endovascular stent-grafts. The total number of aneurysms repaired per year by vascular fellows before the endovascular program was 71.3 +/- 4.9 (range, 68-77) and increased to 124.7 +/- 35.6 (range, 91-162) after introduction of endovascular repair (P <.05). This increase was primarily caused by the addition of endovascular stent-graft repairs by vascular fellows (51.0 +/- 29.0/year [range, 23-81]). There was no change in the number of open infrarenal aortic aneurysm repairs per year, 53.0 +/- 6.6 (range, 48-56) before endovascular repair versus 47.0 +/- 1.7 (range, 46-49) after (P = not significant). There was a significant increase in the number of suprarenal AAA repairs per year by vascular fellows, 10.0 +/- 1.0 (range, 9-11) before endovascular repair compared with 19.0 +/- 6.5 (range, 13-26) after (P <.05). There was no change in the number of thoracoabdominal aneurysm repairs per year between the two groups, 8.0 +/- 3.0 (range, 4-11) before endovascular repair compared with 7.6 +/- 2.3 (range, 5-9) after. CONCLUSIONS: Introduction of an endovascular aneurysm stent-graft program significantly increased the total number of aneurysms treated. Although the number of open aneurysm repairs has remained the same, the complexity of the open aneurysm experience has increased significantly for vascular fellows in training.     

Collagen types and matrix protein content in human abdominal aortic aneurysms

Deficiencies of total collagen, type III collagen, and elastin have been proposed to explain aneurysm formation. Infrarenal aortas were collected from 19 patients (age 70 +/- 7 years) undergoing operative repair of abdominal aortic aneurysms (diameter 7 +/- 2 cm) and from 13 autopsies (age 63 +/- 17 years) of patients without aneurysm disease (controls). Wall thickness and collagen and elastin concentration were determined in full-thickness aorta. Collagen types I and III were measured after digestion with cyanogen bromide, which solubilized nearly 90% of total collagen for typing. Cyanogen bromide peptides were separated by sequential carboxymethylcellulose and agarose chromatography and quantified by peak area measurement with computerized image analysis. Histologic examination revealed prominent inflammatory cell infiltration and deficient, fragmented elastin in the aneurysms. Aortic wall thickness was similar in aneurysms and in control specimens. In the aneurysms, collagen was increased (37% +/- 16% vs 24% +/- 5%; p less than 0.05) and elastin was decreased (1% +/- 1% vs 12% +/- 7%; p less than 0.001), expressed as a percentage of delipidized, decalcified dry weight. Collagen type I accounted for 74% +/- 4% of aneurysm and 73% +/- 4% of control collagen solubilized for typing, and collagen type III accounted for 26% +/- 4% of aneurysm and 27% +/- 4% of control collagen solubilized for typing. Neither patients with a family history of aneurysms nor those without a history of aneurysms had collagen type III deficiency. Atherosclerotic abdominal aortic aneurysms are associated with an inflammatory process and may result from elastin degradation and not a deficiency of type III collagen.     

直肠癌术前动脉插管化疗后手术时机的选择

探讨直肠癌患者术前动脉管化疗后的手术时机。方法对２７例Ｄｕｋｅｓ’Ｂ－Ｃ期直肠癌患者,选择肠系膜下动脉或左髂内动脉,以５－氟脲嘧啶６００ｍｇ／ｍ＾２、丝裂霉素１５ｍｇ／ｍ＾２、表阿霉素３０ｍｇ／ｍ＾２、丝裂霉素１５ｍｇ／     

Cigarette smoking increases aortic dilatation without affecting matrix metalloproteinase-9 and -12 expression in a modified mouse model of aneurysm formation

OBJECTIVE: The development of abdominal aortic aneurysms (AAA) is presumed to result from multiple genetic and environmental factors, with exposure to tobacco smoke the single largest known factor predisposing to aneurysm growth. We have attempted to adapt the elastase-perfused animal model to determine whether tobacco exposure can lower the threshold of aortic injury necessary for AAA development. METHODS: Adult C57BL/6 mice underwent transient perfusion of the infrarenal aorta with an active solution of elastase: high-dose (HDE, 0.19 U/mL, n=9), standard-dose (SDE, 0.16 U/mL, n=21) or low-dose (LDE, 0.07 U/mL, n=24). Control animals (n=24) were treated with heat inactivated elastase (HIE). Twenty LDE perfused mice were exposed to cigarette smoke (LDE-S) beginning 2 weeks before perfusion and continuing until aortic harvest. Aortic diameter (AD) was measured preperfusion, postperfusion, and at harvest on day 14. AAA was defined as %DeltaAD>or=100% between preperfusion and harvest. Aortas from each group (except HDE) were analyzed for matrix metalloproteinase-9 (MMP-9) and MMP-12 expression by real-time polymerase chain reaction normalized to glyceraldehyde-3-phosphate dehydrogenase. RESULTS: All SDE mice developed large AAA by %DeltaAD (189.3%+/-16.9%, mean+/-standard error of the mean), but control mice had only a small dilatation (69.7%+/-3.7%, P<.01). Higher doses of elastase did not produce larger aneurysms in HDE mice. In contrast, only 63% of LDE mice showed aneurysmal dilatation, and these were significantly smaller (104.3%+/-4.2%, P<.01). When exposed to cigarette smoke, LDE animals developed significantly larger aneurysms (%DeltaAD, 134.5%+/-7.9%, P=.0021). There was no difference in normalized aortic MMP-9 and MMP-12 expression between elastase doses or between smoke-exposed and unexposed animals. Histologic analysis revealed that smoking increased the extent of aortic elastin degradation when compared with LDE-S animals. CONCLUSION: Aneurysm development in the elastase model is dependent on the quantity of active elastase infused. Exposure of animals to tobacco smoke after a relatively minor aortic elastase injury produces increases in elastin degradation and aneurysm size without affecting MMP-9 or MMP-12 expression. To our knowledge, this is the first demonstration in an animal model that smoking can act as a synergistic factor in AAA development. Further understanding of the relationship between smoking and AAA in this model may help unveil the pathophysiologic pathways involved between cigarette smoke and AAAs.     

The creation of an infrarenal aneurysm within the native abdominal aorta of swine

BACKGROUND: Models of native abdominal aortic aneurysms (AAA) have been created in rodents using elastase and calcium chloride perfusion. These models, however, do not permit the evaluation of endovascular devices. This study describes the use of mechanical and enzymatic techniques to create native AAA in swine. METHODS: Surgically exposed abdominal aortas of ten male Yorkshire swine (25-35 kg) were dilated, then perfused for 20 min with a 50-mL solution of elastase (30 units) and collagenase (8000 units). Serial magnetic resonance imaging (MRI) at 1, 3, and 6 wk was used to evaluate postoperative aortic diameter. Animals were euthanized at 24 h, 48 h and 1, 2, and 6 wk for histological evaluation. RESULTS: MRI demonstrated an increase in mean aortic diameter by 73.3% +/- 30.2% (33.3-116.7%), which gradually increased postoperatively. Partial endothelial loss, mural neutrophil infiltrate, and elastin disruption were evident (1, 3, and 7 days). Smooth muscle cell attrition occurred within the inner tunica media (7 days). Collagen deposition, limited SMC repopulation and luminal reendothelialization appeared at 3-6 wk. Elastin injury persisted. CONCLUSIONS: The creation of an infrarenal aneurysm is possible within the native aorta of swine. After aneurysm creation, progressive increase in aortic diameter was detectable. Further evaluation will be necessary to more completely characterize the nature and extent of elastase-induced porcine aortic aneurysmal degeneration.     

Collagen and elastin gene expression in aortic aneurysms.

BACKGROUND. The decreased elastin concentration found in abdominal aortic aneurysms (AAAs) may result from a differential synthetic response wherein elastin gene expression fails to increase in parallel with type I procollagen (COL I) gene expression. The purpose of this study is to determine tissue mRNA levels for elastin and COL I in AAAs compared with levels in normal, age-matched aorta and to determine the relationship between aging and COL I gene expression. METHODS. Total RNA exacted from normal infrarenal aortic tissue (n = 7) and AAA (n = 10) tissue was subjected to Northern analysis. Mean values for COL I, elastin, and alpha-tubulin mRNA levels were compared by use of the Student t test. Age and COL I mRNA levels were analyzed by regression analysis. RESULTS. COL I mRNA was increased significantly in AAAs (1.18 +/- 0.13) compared with normal aortas (0.14 +/- 0.05). A commensurate increase in elastin mRNA (AAAs, 0.11 +/- 0.02, vs normal aortas, 0.39 +/- 0.2) was absent. There was no correlation between age and COL gene expression. CONCLUSIONS. The decreased elastin concentration relative to collagen in AAAs may be explained, in part, by the changes in message level of elastin and collagen. The enhanced COL I gene expression in AAAs is unrelated to age.     

Matrix metalloproteinase 8 (neutrophil collagenase) in the pathogenesis of abdominal aortic aneurysm

BACKGROUND: Loss of elastin is the initiating event in abdominal aortic aneurysm (AAA) formation, whereas loss of collagen is required for continued expansion. The elastolytic matrix metalloproteinases (MMPs) 2 and 9 are well described, but the source of excessive collagenolysis remains undefined. The aim of this study was to determine the expression of MMP-8, a potent type I collagenase, in normal aorta and AAA. METHODS: Infrarenal aortic biopsies were taken from 40 AAA and ten age-matched normal aortas. The concentrations of MMP-8 protein and its inhibitors, tissue inhibitor of metalloproteinase (TIMP) 1 and TIMP-2, were quantified by enzyme-linked immunosorbent assay. Immunohistochemistry was used to localize MMP-8 expression. RESULTS: MMP-8 concentrations were significantly raised in AAA compared with normal aorta (active MMP-8: 4.5 versus 0.5 ng per mg protein, P < 0.001; total MMP-8: 16.6 versus 2.8 ng per mg protein, P < 0.001). Levels of TIMP-1 and TIMP-2 were significantly lower in AAA than in normal aortic samples (TIMP-1: 142.2 versus 302.8 ng per mg protein; P = 0.010; TIMP-2: 9.2 versus 33.1 ng per mg protein, P < 0.001). Immunohistochemistry localized MMP-8 to mesenchymal cells within the adventitia of the aortic wall. CONCLUSION: The high concentration of MMP-8 in aortic aneurysms represents a potent pathway for collagen degradation, and hence aneurysm formation and expansion.     

Mitochondrial-dependent apoptosis in experimental rodent abdominal aortic aneurysms

OBJECTIVES: While extrinsic mechanisms of apoptosis in abdominal aortic aneurysms (AAAs) are recognized, this project hypothesizes that an intrinsic, mitochondrial-dependent, mechanism of apoptosis also contributes to experimental AAA formation. METHODS: Rat aortas were perfused with either saline or elastase (N = 5 per group) and harvested 7 days postperfusion. The aortas were placed in gluteraldehyde for subsequent transmission electron microscopy, Bouin's solution for TUNEL, or paraformaldehyde for immunohistochemical staining for caspase-9, caspase-3, and Bid. RESULTS: Abdominal aortic diameters increased 168 +/- 25% (mean +/- SEM) after elastase perfusion. compared with 30 +/- 5% after saline perfusion (P < .001). Apoptosis of aortic smooth muscle cells, macrophages, and neutrophils was evidenced by transmission electron microscopy and TUNEL in the elastase-perfused aneurysmal aortas. Quantitative analysis of the apoptotic cells revealed a significant (P < .01) increase in the number of total apoptotic cells in the elastase-perfused aortas (12 +/- 3 cells per high-power field), compared with that of saline-infused controls (1.3 +/- 0.2). Caspase-9, the key initiator in the mitochondrial-dependent apoptotic pathway, stained positively in only elastase-perfused aortas. Bid staining was not detected in either the elastase-perfused aortas or the saline controls. CONCLUSIONS: Apoptosis is evident in multiple cell lines in elastase-perfused aneurysmal aortas, but rarely observed in control aortas. Caspase-9, the key initiator of intrinsic apoptosis, was documented only in elastase-perfused aortas. These results suggest that mitochondrial-dependent apoptosis is associated with abdominal aortic aneurysm formation.     

肾动脉下腹主动脉瘤腔内治疗后并发症的防治

目的　总结肾动脉下腹主动脉瘤腔内治疗后常见并发症的预防与处理。　方法对已施行腔内治疗的 71例肾下腹主动脉瘤患者的临床资料进行回顾性分析 ,讨论常见并发症发生的原因、处理、结果及预后。　结果　 71例接受腔内治疗的肾动脉下腹主动脉瘤患者技术成功率1 0 0 % ,无中转开腹手术者。原发性内漏 8例 ,神经并发症合并急性血栓形成 1例。一过性缺血性肠炎 2例。无肾动脉梗死、肢体栓塞等并发症。平均随访时间 (2 6± 5)个月。围手术期病死率 1 3 % (1 /71 ) ,总病死率 4 2 % (3/ 71 )。死亡原因 2例为急性心肌梗死 ,1例为急性心功能衰竭。随访过程中发现 3例原发性内漏转为持续性内漏 ,另发现继发性内漏 4例。本组患者 1个月后内漏发生率 9 8%(7/ 71 )。 2例继发性Ⅰ型内漏随访中瘤体增大 ,1例进行二期腔内治疗。　结论　动脉瘤的腔内治疗具有创伤小、技术操作可行、效果肯定的优点 ,内漏血是该技术主要并发症。对漏血量及瘤体有增大趋势的内漏应积极处理     

Expression of integrin alpha5beta1 and the relationship to collagen and elastin content in human suprarenal and infrarenal aortas

The infrarenal aorta is especially prone to the development of aneurysm, suggesting an intrinsic structural and molecular difference in different parts of the aorta. Previous study from this laboratory has implicated a potential role of integrin alpha5beta1 in maintaining aortic integrity. The aim of this study was to investigate the expression of integrin alpha5beta1 and the relationship to collagen and elastin content between 2 different aortic segments. In this study, the variation of smooth muscle cells and the localization of integrin alpha5beta1 in the suprarenal and infrarenal aorta tissues removed from organ donors were studied immunohistochemically. The biochemical analysis for matrix proteins and integrin alpha5beta1 protein was done by Western Blot on the corresponding tissues. All interested protein content was normalized to the smooth muscle alpha-actin protein. No significant difference of smooth muscle cells density between the 2 segments of aortas was observed. Integrin alpha5beta1 was localized in the outer layer of all aortic media. The authors found that the ratio of collagen/elastin in infrarenal aortas was significantly increased 2-fold because elastin content in infrarenal aortas decreased 49% as compared with suprarenal aortas. Integrin alpha5beta1 content relative to its specific ligand-collagen-did not differ between these 2 different aortic segments. These results suggest that the infrarenal aorta differed biochemically from the suprarenal aorta. A decrease in infrarenal elastin without a corresponding decrease in collagen and integrin alpha5beta1 may affect the compliance and integrity of the distal aorta. These intrinsic anatomic differences may be important in the susceptibility of the infrarenal aortas to aneurysm formation.     

Fate of the ectatic infrarenal aorta: expansion rates and outcomes

The natural history of the ectatic infrarenal aorta remains undetermined. While surveillance protocols have been proposed for true aneurysms, no recommendations are currently available for ectatic aortas. The purpose of this study is to define the natural history and recommend surveillance protocols for the infrarenal aorta 2.5-2.9 cm in diameter. Screening of 12,500 yielded 223 patients with an infrarenal abdominal aorta 2.5-2.9 cm in diameter at a university-affiliated VA medical center. All patients were prospectively followed by ultrasound from August 1993 through October 2000 and expansion rates were calculated by comparing the first and last study. Multivariate analysis of risk factors classically associated with abdominal aortic aneurysm was performed. Current data suggest that ectatic infrarenal aortas expand slowly, do not rupture, and rarely meet criteria for operative repair. No risk factors linked to the development of aneurysms were identified. On the basis of this study we recommend that patients with ectatic aortas have a repeat ultrasound 5 years after the initial study.     

The role of inflammation in nonspecific abdominal aortic aneurysm disease

The predominant pathologic feature of abdominal aortic aneurysm is elastin destruction, and elastin destruction may be mediated by inflammation. In this investigation serial sections of abdominal aortic aneurysm specimens were selectively stained to study the relationship between inflammation and elastin degradation. In addition, soluble aortic extracts were examined for the presence of immunoglobulins. An inflammatory infiltrate was present in 8 of 10 of the abdominal aortic aneurysm specimens examined. The infiltrate was mononuclear, commonly located at the junction of the media and adventitia; it did not codistribute with loss of elastin. The presence of an inflammatory component in abdominal aortic aneurysm was associated with a large amount of immunoglobulin in soluble extracts from aneurysmal tissue compared to atherosclerotic and normal control extracts. This study further characterizes the microscopic pathology of abdominal aortic aneurysm and describes the presence of immunoglobulin in soluble tissue extracts. In addition, the possible role of inflammation in abdominal aortic aneurysm as it relates to protease expression is detailed. Presented in part at the meeting of the New England Vascular Society, September 21–22, 1989, Bretton Woods, New Hampshire.     

Inflammatory abdominal aortic aneurysm treated by endovascular stent grafting: a case report

Despite complications inherent to open surgical repair of inflammatory abdominal aortic aneurysms, there is expected resolution of the retroperitoneal inflammatory process following graft replacement. An endovascular approach could also exclude the aneurysm while potentially avoiding injury to vital structures in the hostile operative field. However, data are limited regarding the role of endovascular stent grafts in the management of inflammatory abdominal aortic aneurysms. Furthermore, postoperative regression of perianeurysmal inflammation is rarely discussed in the few published accounts of endovascular repair of inflammatory aortic aneurysms. The case presented demonstrates successful endovascular treatment of an infrarenal inflammatory aneurysm with resolution of the retroperitoneal inflammation and hydronephrosis.     

Experience with endovascular grafts in the treatment of infrarenal aortic aneurysms associated with proximal aortic dissection

BACKGROUND: Chronic abdominal and thoracic aortic dissections often present with concomitant infrarenal aortic dilatation. We conducted a retrospective review of 6 patients treated with endovascular stent grafts for coexisting aortic dissection and infrarenal aneurysm. METHODS: Six patients with suprarenal aortic dissections and infrarenal aortic aneurysms (AAA) had their AAAs treated with endovascular grafts. Grafts were constructed of balloon expandable Palmaz stents and expanded polytetrafluoroethylene graft. The device was inserted transfemorally and deployed under fluoroscopy. RESULTS: Successfully primary AAA exclusion was achieved in 5 patients. One patient required a supplemental stent placed above the endograft and into the true lumen to seal the endoleak. No aneurysm has enlarged, and all remain thrombosed for 9 to 24 months (mean 20). One type III dissection enlarged 2 weeks after endograft insertion. One patient had uncomplicated cephalad fenestration of a dissection by the endograft. CONCLUSIONS: Endovascular grafts may be used to treat coexisting AAA and aortic dissection. Attention to the site or sites of reentry of a dissection is essential to insure full aortic aneurysm exclusion. The fate of a chronic aortic dissection cephalad to an endovascularly treated AAA is unclear and will require longer follow-up.     

Inhibition of inducible nitric oxide synthase limits nitric oxide production and experimental aneurysm expansion

PURPOSE: Nitric oxide (NO), frequently cited for its protective role, can also generate toxic metabolites known to degrade elastin. Both abdominal aortic aneurysms (AAAs) and inducible nitric oxide synthase (iNOS) are associated with inflammatory states, yet the relationship between NO production by iNOS and AAA development is unknown. The current study examines iNOS expression, NO production, and the effects of selective inhibition of iNOS by aminoguanidine in experimental AAA. METHODS: An intra-aortic elastase infusion model was used. Control rats received intra-aortic saline infusion and postoperative intraperitoneal saline injections (Group 1). In the remaining groups, intra-aortic elastase infusion was used to induce aneurysm formation. These rats were treated with intraperitoneal injections of saline postoperatively (Group 2), aminoguanidine postoperatively (Group 3), or aminoguanidine preoperatively and postoperatively (Group 4). Aortic diameter and plasma nitrite/nitrate levels were measured on the day of surgery and postoperative day 7. Aortas were harvested for biochemical and histologic analysis on postoperative day 7. RESULTS: Infusion of elastase produced AAAs (P <.001) with significant production of iNOS (P <.05) and nitrite/nitrate (P <.003) compared with controls. Selective inhibition of iNOS with aminoguanidine in elastase-infused aortas significantly reduced aneurysm size (P <.01) compared with elastase infusion alone. Aminoguanidine-treated rats displayed suppression of iNOS expression and plasma nitrite/nitrate production not significantly different from the control group. Histologic evaluation revealed equivalent inflammatory infiltrates in elastase-infused groups. CONCLUSION: Expression of iNOS is induced and plasma nitrite/nitrate levels are increased in experimental AAA. Inhibition of iNOS limits NO production and iNOS expression, resulting in smaller aneurysm size. NO production by iNOS plays an important role with detrimental effects during experimental aneurysm development.