Relationship between coagulation cascade, cytokine, adhesion molecule and aortic aneurysm

Objectives: Patients with aortic aneurysm (AA) were in the chronic inflammatory condition and are often combined with disseminated intervascular coagulation. Recent studies demonstrated that atherosclerosis was inflammatory disease. AA and severe atherosclerosis with ulcer formation contain macrophages and T lymphocytes and accelerate the production of interleukin (IL)-2, which activates lymphocytes and lead to further adhesion of leukocytes. This study was designed to clarify the coagulation condition, cytokine, adhesion molecule, and collagen turnover in patients with AA and finally their relationship with the aneurysmal size. Methods: Thrombin–antithrombin III complex (TAT), plasma D-dimer, serum type III procollagen peptide (PIIIP), serum soluble IL-2 receptor (sIL-2R), Free tissue factor pathway inhibitor (TFPI), and soluble intercellular adhesion molecule (ICAM-1) were measured preoperatively around the same period when computed tomography (CT) was taken in 17 patients with AA (mean age: 72.2 years). Age-matched (mean age:70 years) volunteers were served as control. Maximum aneurysmal size was measured by CT and aneurysmal volume was also calculated from CT. Results: AA patients showed significantly higher level in preoperative TAT and D-dimer compared to control (TAT: control 2.5±1.2 ng/ml, pre 7.2±4.5, ng/ml; P=0.0001; D-dimer: control 107±46 U/ml, pre 420±256 U/ml; P=0.0001). Cytokine also showed higher level preoperatively (sIL-2R: control 398±132 U/ml, pre 735±260 U/ml; P=0.0001). TFPI showed higher value preoperatively (control 22.9±4.9 ng/ml, pre 30.4±6.9 ng/ml; P=0.003). PIIIP (collagen turnover) showed no difference between the groups (P=0.0057) and neither did ICAM-1(P=0.0087). TAT (r=0.799, P=0.0001), D-dimer (r=0.56, P=0.0193), sIL-2R (r=0.709, P=0.0021), PIIIP (r=0.561, P=0.00239), and sICAM-1 (r=0.505, P=0.046) level showed positive correlation with aortic aneurysmal size and also TAT D-dimer, and sIL-2R levels were positively correlated with aneurysmal volume (r=0.714 P=0.0013, r=0.556 P=0.00204, r=0.693 P=0.0029, respectively). Conclusions: AA patients were in the hypercoagulation and inflammatory condition. Aneurysmal size was well correlated with TAT, D-dimer, sIL-2R, PIIIP, and sICAM-1, suggesting that these markers could be good diagnostic and monitoring tool for the disease progression.     

Activated coagulation during open and endovascular abdominal aortic aneurysm repair

OBJECTIVE: The study was conducted to determine activation of coagulation in patients undergoing open and endovascular infrarenal abdominal aortic aneurysm repair (EVAR). METHODS: In a prospective, comparative study, 30 consecutive patients undergoing open repair (n = 15) or EVAR (n = 15) were investigated. Blood samples to determine fibrinopeptide A, fibrin monomer, thrombin-antithrombin complex, and D-dimer were taken up to 5 days postoperatively. Routine hematologic and hematochemical parameters as well as clinical data were collected. RESULTS: Both groups showed comparable demographic variables. Operating time was longer in open repair (249 +/- 77 minutes vs 186 +/- 69 minutes, P < .05). Perioperatively elevated markers of coagulation were measured in both groups. Fibrinopeptide A levels did not differ significantly between the groups (P = .55). The levels of fibrin monomer and thrombin-antithrombin complex were significantly higher in patients undergoing EVAR (P < .0001), reflecting increased thrombin activity and thrombin formation compared with open surgery. The D-dimer level did not differ significantly between the groups. These results were also valid after correction for hemodilution. CONCLUSION: These data suggest increased procoagulant activity in EVAR compared with open surgery. A procoagulant state may favor possible morbidity derived from micro- and macrovascular thrombosis, such as in myocardial infarction, multiple organ dysfunction, venous thrombosis and thromboembolism, or disseminated intravascular coagulation.     

腹主动脉瘤血管腔内治疗与开放手术治疗的疗效比较

目的 比较腹主动脉瘤血管腔内治疗与开放手术治疗的近期疗效。方法 对34例肾下型腹主动脉瘤患者的临床资料进行分析，比较腔内治疗组（15例）与传统开放手术治疗组（19例）的术前状况、手术相关情况、术后并发症、死亡率及手术前后的实验室检查数据。结果 腔内组术中出血量和输血量明显少于手术组（P=0．005、P=0．015），腔内组术后平均禁食时间和平均住院时间较手术组明显缩短（P〈0．0l、P：0．001）。手术组术后并发症发生率明显高于腔内组（P〈0．01）。术后第3天白细胞计数腔内组明显低于手术组（P=0．020）；术后第5天红细胞计数及血肌酐水平在腔内组均明显高于手术组（P=0．011、P=0．034）。结论 腹主动脉瘤血管腔内治疗具有安全、微创、对人体内环境干扰小的优点，近期疗效较传统开放手术好。     

Thoracovisceral segment aneurysm repair after previous infrarenal abdominal aortic aneurysm surgery

OBJECTIVE: Repair of thoracovisceral aortic aneurysms (TVAA) after previous open repair of an infrarenal abdominal aortic aneurysm (AAA) poses significant challenges. We sought to better characterize such recurrent aneurysms and to evaluate their operative outcome. METHODS: We reviewed the records and radiographs of 49 patients who underwent repair of TVAAs between 1988 and 2002 after previous repair of an AAA. Visceral artery reconstructions were completed with combinations of beveled anastomoses, inclusion patches, and side arm grafts. In 14 patients visceral endarterectomy was required to treat associated occlusive disease. Sixteen patients had cerebrospinal fluid drainage, and 10 patients had distal perfusion during cross-clamping. RESULTS: Patient mean age was 72 years, and 80% were men. Fifty-one percent of patients had symptomatic disease, and average TVAA diameter was 6.2 cm. Mean time between AAA and TVAA repair was 77 months. Twenty-six percent of aneurysms were restricted to the lower visceral aortic segment, 35% extended to the diaphragm, another 35% extended to the distal or middle thoracic aorta, and 4% involved the entire remaining visceral and thoracic aorta. The 30-day operative mortality rate was 4.1% in patients with nonruptured aneurysms and 50% in patients with ruptured aneurysms, for an overall mortality rate of 8.2%. Fifteen patients (30.6%) had major morbidity, including paresis in two patients and dialysis-dependent renal failure in five patients. At late follow-up, three patients required further aortic operations to treat additional aneurysms, and four patients had fatal aortic ruptures. Two-year and 5-year cumulative survival rates were 61% (+/-7.5%) and 37% (+/-7.8%), respectively. At univariate analysis, operative blood loss was the sole significant predictor of major morbidity (P <.023), and rupture (P <.030, P <.0001) and aneurysm extent (P <.0007, P <.0001) correlated with both operative death and long-term survival. Only aneurysm extent (P <.010, relative risk 37.3) remained a significant predictor of long-term survival at multivariate analysis. CONCLUSION: Elective repair of TVAAs after previous AAA repair can be performed with an acceptable level of operative mortality, though with considerable operative morbidity. Limited long-term survival mandates careful patient selection, and the high mortality associated with ruptured TVAA underscores the need for post-AAA surveillance.     

Increased nitrotyrosine production in patients undergoing abdominal aortic aneurysm repair

BACKGROUND: Vascular inflammation is implicated in the pathogenesis of atherosclerosis and abdominal aortic aneurysm (AAA), and is thought to involve reactive species such as the nitric oxide-derived oxidant peroxynitrite. In the present study nitrotyrosine was measured as a stable marker of peroxynitrite production in vivo. METHODS: Perioperative blood samples were obtained from patients undergoing elective open or endovascular repair of an AAA and from patients with intermittent claudication, smoking aged-matched controls, non-smoking aged-matched controls and non-smoking young healthy controls. Plasma nitrotyrosine was measured by an enzyme-linked immunosorbent assay. RESULTS: The median plasma nitrotyrosine concentration in patients with an AAA (0.46 nmol nitrated bovine serum albumin equivalents per mg protein) was significantly higher than that in patients with intermittent claudication (0.35 nmol; P = 0.002), smoking controls (0.36 nmol; P = 0.001), non-smoking controls (0.35 nmol; P = 0.002) and young healthy controls (0.27 nmol; P < 0.001). Nitrotyrosine concentrations increased during early reperfusion in open AAA repair, but not during endovascular repair. AAA exclusion from the circulation reduced levels to control values (P = 0.001). CONCLUSION: Patients with an AAA had raised levels of circulating nitrated proteins compared with patients with claudication and controls, suggesting a greater degree of ongoing inflammation that was not related to smoking.     

高风险患者腹主动脉瘤手术与腔内治疗效果的比较

目的 比较高风险患者腹主动脉瘤(abdominal aortic aneurysm,AAA)手术治疗(opensurgical repair,OSR)与腔内治疗(endovascular aneurysm repair,EVAR)的效果,探讨高风险患者AAA治疗方式的选择.方法 利用(customized probability index,CPI)危险评分方法[1]筛选出我院1998年至2008年高风险患者55例,比较OSR组(20例)与EVAR组(35例)围手术期及术后近期结果.结果 OSR组随访率100%,平均随访6年3个月.EVAR组随访率94%,平均随访5年10个月.(1)手术时间高风险患者EVAR组(3.1±0.6)h短于OSR组[(4.9±0.9)h(P<0.05)];(2)EVAR组术中出血、ICU时间和住院时间均短于OSR组(P<0.01);(3)围手术期死亡率EVAR组(2.86%)明显低于OSR组(15.00%);(4)术后并发症发生率EVAR组(17%)明显低于OSR组(40%);(5)EVAR组术后并发症主要为内漏(8.57%);(6)OSR组并发症主要为心脏相关性疾病(25%).结论 EVAR对于高风险患者AAA的治疗可以更少的导致围手术期心血管事件的发生,降低围手术期的死亡率和并发症发生率.CPI可以相对准确评估血管手术围手术期死亡率和并发症的发生率,可用于指导围手术期的治疗策略.     

Pro- and anti-inflammatory cytokine release in open versus endovascular repair of abdominal aortic aneurysm

BACKGROUND: Pro- and anti-inflammatory cytokine release occurs with abdominal aortic aneurysm (AAA) repair although the relative contribution of each is currently poorly understood. Ischaemia-reperfusion injury is thought to play a greater role following open (OR) than endovascular (ER) repair, with resultant greater perioperative morbidity. METHODS: Thirty-two patients undergoing OR (n = 16) and ER (n = 16) of AAA were studied. Systemic venous (SV) blood was taken at induction (baseline), 0 h (last clamp off), 4, 24, 72 and 144 h, and femoral venous (FV) blood (indwelling catheter; lower torso venous effluent) at 0, 4 and 24 h. The cytokines interleukin (IL) 6, IL-8 and IL-10 were measured in these samples. RESULTS: In OR, SV and FV IL-6 increased from baseline to a peak at 24 h (SV 589 pg/ml (P = 0.001 versus baseline) and FV 848 pg/ml (P = 0.05)) before declining at 144 h. In ER, there was a similar pattern but the increase was smaller (24 h: SV 260 pg/ml (P = 0.003 versus baseline) and FV 319 pg/ml (P = 0.06)) at all equivalent timepoints compared with OR. IL-8 peaked earlier (4 h) from baseline in both groups before declining by 144 h, and significant differences between SV and FV were seen only in the OR group. IL-10 levels peaked in both groups at 24 h before declining at 144 h, and there were no significant locosystemic differences between the groups. CONCLUSION: Venous pro-inflammatory cytokine changes (IL-6) are consistent with significantly greater lower-torso reperfusion injury in patients undergoing OR. Smaller responses were seen after ER (IL-6 and IL-8), although both groups showed a similar anti-inflammatory response (IL-10); this pro- and anti-inflammatory imbalance may account for the increased morbidity associated with OR.     

腹主动脉瘤中细胞黏附分子差异表达的研究

目的研究腹主动脉瘤 (AAA)中细胞黏附分子的差异表达与AAA发病的关系。方法利用基因芯片技术筛查AAA和正常腹主动脉中差异表达的细胞黏附分子基因 ,再利用分子生物学方法在基因、蛋白质水平检测。结果AAA中有 3种细胞黏附分子存在差异表达 ,它们是VCAM 1,PECAM 1,TSP ,上调比率分别达到 5 7,3 6及 5 7 4倍。结论AAA中有细胞黏附分子的表达差异 ,差异表达基因可能在AAA的发病过程中起作用     

Percutaneous repair of abdominal aortic aneurysm

OBJECTIVE: Percutaneous treatment of an abdominal aortic aneurysm (AAA) is feasible, but is associated with a unique set of risks. A comparison of Excluder endograft deployment with femoral artery cutdown (FAC) versus percutaneous femoral access (PFA) for treatment of infrarenal AAA was undertaken. METHODS: A single-institution, controlled, retrospective review was carried out in patients who underwent either bilateral FAC or bilateral PFA for endovascular repair of infrarenal AAA with the Gore bifurcated Excluder endograft between March 1999 and November 2003. To November 2000, 35 patients underwent bilateral FAC; since then, 47 patients have undergone bilateral PFA. All have been followed up for at least 30 days. RESULTS: Mean AAA size was 5.7 cm in the FAC group and 6.0 cm in the PFA group. During hospitalization there were six access-related complications in the FAC group; three required early surgical intervention. In the PFA group nine perioperative access-related complications occurred, all consisting of either hemorrhage or arterial occlusion; seven required additional intervention, and were recognized and ameliorated while the patient was still in the operating room. At 30-day follow-up there were no additional access-related complications in the PFA group. There were eight other access-related complications in eight additional patients who underwent FAC. In patients undergoing bilateral PFA total operative time was shorter (PFA 139 minutes vs FAC 169 minutes; P =.002), total in-room anesthesia time was less (PFA 201 minutes vs FAC 225 minutes; P <.008), and use of general anesthesia was reduced (P <.001). No significant differences were observed between groups with respect to estimated blood loss (PFA 459 mL vs FAC 389 mL; P =.851). CONCLUSION: Complete percutaneous treatment of AAA may have some advantages over open femoral artery access, but it is not free from risk. Percutaneous treatment of AAA can be completed successfully in most patients, but should be performed at an institution where conversion to an open procedure can be completed expeditiously if necessary.     

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应用跨肾动脉支架人工血管腔内修复术治疗腹主动脉瘤,并探讨其手术适应证,操作要点及并发症的预防。方法对２例病人采用全麻,在动态数字减影血管造影监测下用跨肾动脉支架分叉型人工血管对腹主动脉瘤进行了腔内修复术,结果手术中ＤＳＡ提示动脉瘤消失,无内漏发生。术后１周及分别随访３和９个月,螺旋ＣＴ检查提示腔内人工血管无移位扭曲,血流通畅无内漏发生,结论腹主动脉瘤腔内修复术手术创伤小,病人恢复快,跨肾动支架人工     

Changes in coagulation condition, cytokine, adhesion molecule after repair of type A aortic dissection.

OBJECTIVE: Because residual dissection often exists even after the repair of a type A dissection, we evaluated coagulation conditions, cytokine levels, and adhesion molecule levels in mid-term follow up after repair of type A dissections. METHODS: Thrombin-antithrombin III complex (TAT), D-dimer, soluble interleukin-2 receptor (sIL-2R), soluble intercellular adhesion molecule (sICAM)-1, and type III procollagen peptide (PIIIP) were measured in 12 patients (mean age=63 years) following the repair of a type A aortic dissection at 6-82 months after repair (median=33 months). RESULTS: In the chronic phase, TAT and D-dimer were significantly higher in patients following the repair of a type A dissection compared to healthy controls (TAT; 12+/-8 vs. 2.5+/-1.2 ng/ml, P = 0.0001, D-dimer; 779+/-1384 vs. 104+/-46 U/ml, P = 0.0001). Cytokine was significantly higher in the affected patients (sIL-2R; 556+/-205 vs. 398+/-132 U/ml, P = 0.003, sICAM-1; 255+/-131 vs. 211+/-48 ng/ml, P = 0.136). Collagen turnover (PIIIP) showed a significantly higher value in the affected patients (0.80+/-0.32, vs. 0.58+/-0.13 U/ml, P = 0.002). sIL-2R, sICAM-1 and PIIIP showed a negative correlation with the follow-up period (sIL-2R; r = -0.733, P = 0.0067, sICAM-1; r = -0.61, P = 0.035, PIIIP; r = -0.692, P = 0.0126). We found a positive correlation between aortic size and TAT (r = 0.644, P = 0.0238, n = 12) as well as with D-dimer (r = -0.7831, P = 0.0106, n = 12) and TAT showed significantly higher values in the residual dissection group compared to those without residual dissection (16.6+/-7.9 vs. 7.45+/-4.75 ng/ml, P = 0.035). CONCLUSION: Hypercoagulation conditions continued even after repair. Both TAT and D-dimer would be good indices for following up patients having repaired aortic dissections. Furthermore, cytokine, adhesion molecules, and collagen turnover would return to a stable state unless impairment and expansion of the vessel wall occurred.     

Endovascular abdominal aortic aneurysm repair in women

The objective of this review is to establish the role of endovascular aortic aneurysm repair (EVAR) in women. A step by step approach is taken looking at sex and gender differences in epidemiology, pathogenesis and natural history. We then proceed to discuss the results from the three randomized controlled trials comparing EVAR to open repair. Finally, sex-specific secondary prevention, risk factor management and medication, is discussed. Women seem to have higher mortality and more complications after EVAR. Risk factors such as diabetes and hypertension are associated with worse outcome in women compared to men. The role of EVAR in women is poorly investigated and its definite role remains to be determined. Aggressive treatment of risk factors and the optimisation of medication in women are indicated and deserve more attention in clinical practice and future research.     

Colon ischemia following abdominal aortic aneurysm repair in the era of endovascular abdominal aortic repair

OBJECTIVE: To review, in the era of endovascular abdominal aortic repair (EVAR), the clinical spectrum of colonic ischemia (CI) following abdominal aortic aneurysm (AAA) repair and to assess the rate, overall mortality, and associated factors of occurrence. METHODS: Between 1995 and 2005, 1174 patients with infrarenal AAA were treated either by open surgery (n = 682) or by EVAR (n = 492). Preoperative risk factors, clinical presentation, intraoperative data, and early postoperative outcomes were prospectively assessed. Overt colonic ischemia as proven by colonoscopy and/or by operation was considered as a validating event and was correlated to collected variables. RESULTS: CI occurred in 34 patients (2.9%). Eighteen out of 34 (53%) patients died within 1 month. At 2 years, the survival rate was 35% in the CI group vs 86% in the non-CI group. Associated factors of occurrence of CI were: type of operation (open group = 27/682 [4%] vs EVAR = 7/492 [1.4%] [P = .01]), aneurysm rupture (11/88 [12.5%] vs 23/1086 [2.1%], P < .001), preoperative renal insufficiency (4/30 [13.3%] vs 29/1133 [3.1%], P = .01), preoperative respiratory insufficiency (8/157 [7%] vs 23/1005 [2%], P = .01), duration of operation (<2 hours [518] = 1.7%, between 2 to 4 hours [558] 2.9%, more than 4 hours [66] 13.6%, P = .001). Mean blood loss was greater in patients with CI (CI = 2000 ml [650-3350] than in those without CI = 1000 ml [500-1800] P = .008). Logistic regression analysis showed that rupture (OR 6.03 [interval of confidence (IC) 95% 2.68-13.5] P = .0001), duration of operation (OR 5.73 [IC 95% 2.06-15.9] P = .001) and creatinin > 200 mol/l (OR 4.67 [IC 95% 1.39-15.7] P = .028) were independent factors of CI. The mortality due to colonic ischemia was not statistically different between open surgery 14/27 (52%) and EVAR 4/7 (57%). CONCLUSION: CI remains a serious complication following AAA repair. In the univariate analysis, EVAR was associated with a lower rate of colonic ischemia. However, the logistic regression analysis showed that only rupture, long duration of operation, and prior renal disease were independently associated with CI. Within the two treatment modalities, the mortality rate remained identical.     

Endovascular repair of late abdominal aortic aneurysm rupture owing to mixed-type endoleak following endovascular abdominal aortic aneurysm repair

We report the successful endovascular repair of a ruptured abdominal aortic aneurysm (AAA) in a multimorbid patient 8 months after endovascular abdominal aortic aneurysm repair (EVAR). A 74-year-old man with a history of EVAR 8 months earlier presented with hypotension, severe back pain, and tenderness on abdominal palpation. A contrast-enhanced computed tomographic scan showed a large retroperitoneal hematoma and confirmed the diagnosis of secondary abdominal aortic rupture. Because the patient had severe comorbidities, the endovascular method was chosen for further management. Two stent grafts were placed appropriately to eliminate a type 1a and a type 3 endoleak owing to modular separation of the left iliac graft limb from the main body stent graft. An additional self-expanding stent was deployed in the solitary right renal artery to open its origin, which was partially overlapped by the proximal cuff. The patient was discharged on the tenth postoperative day and is alive and well 1 year postoperatively. This case indicates that endovascular repair is feasible not only in cases of primarily ruptured AAAs but also in secondarily ruptured AAAs after failure of EVAR.     

Cost-effectiveness of endovascular abdominal aortic aneurysm repair

BACKGROUND: The rapid introduction of endovascular abdominal aortic aneurysm repair (EVAR) has considerable implications for the management of abdominal aortic aneurysm (AAA). This study was undertaken to determine an optimal strategy for the use of EVAR based on the best currently available evidence. METHODS: Economic modelling and probabilistic sensitivity analysis considered reference cases representing a fit 70-year-old with a 5.5-cm diameter AAA (RC1) and an 80-year-old with a 6.5-cm AAA unfit for open surgery (RC2). Results were assessed as incremental cost-effectiveness ratio (ICER) compared with open repair (RC1) or conservative management (RC2). RESULTS: In RC1 EVAR produced a gain of 0.10 quality-adjusted life years (QALYs) for an estimated cost of 11,449 pound, giving an ICER of 110,000 pound per QALY. EVAR consistently had an ICER above 30,000 pound per QALY over a range of sensitivity analyses and alternative scenarios. In RC2 EVAR produced an estimated benefit of 1.64 QALYs for an incremental cost of 14,077 pound giving an incremental cost per QALY of 8579 pound. CONCLUSION:: It is unlikely that EVAR for fit patients suitable for open repair is within the commonly accepted range of cost-effectiveness for a new technology. For those unfit for conventional open repair it is likely to be a cost-effective alternative to non-operative management. Sensitivity analysis suggests that research efforts should concentrate on determining accurate rates for late complications and reintervention, particularly in patients with high operative risks.     

Comparison of perioperative factors of elective abdominal aortic aneurysm surgery and those of ruptured abdominal aortic aneurysm surgery

BACKGROUND: Currently the mortality rate of elective abdominal aortic aneurysm (eAAA) surgery has improved. However the mortality rate of ruptured abdominal aortic aneurysm (rAAA) surgery remains high. We compared perioperative variables of eAAA surgery and those of rAAA surgery. METHODS: From 1997 to 2002, 98 consecutive patients who had undergone graft replacement of infrarenal AAA (56 eAAA and 42 rAAA) were evaluated retrospectively. RESULTS: Significant differences existed between eAAA and rAAAs in following perioperative variables: agg (eAAA: 74.2 +/- 6.8 years, rAAA: 74.2 +/- 8.6 years), duration from the admission to the time of starting operation (eAAA: 62 +/- 11 min, rAAA: 28 +/- 17 min), duration from the time of starting operation to the aortic cross clamping (eAAA: 87 +/- 29 min, rAAA: 29 +/- 32 min), duration of the aortic cross clamping (eAAA:59 +/- 19 min, rAAA: 71 +/- 29 min), blood loss (eAAA: 1297 +/- 1046 ml, rAAA: 4619 +/- 4960 ml), total amount of blood products required (eAAA: 1058 +/- 953 ml, rAAA: 5619 +/- 4945 ml), intensive and/or high care unit stay (eAAA: 1.8 +/- 1.2 days, rAAA: 6.4 +/- 8.1 days), the postoperative mortality rate (eAAA: 0%, rAAA: 19%), and postoperative complications (eAAA: 14%, rAAA: 48%), CONCLUSIONS: Patients who had undergone rAAA surgery had higher mortality and more postoperative complications than those after eAAA surgery. Elective rapair before AAA ruptures is recommended.