Blocking Interleukin-1 Beta Reduces the Evolution of Thoracic Aortic Dissection in a Rodent Model.

OBJECTIVE: Thoracic aortic dissection (TAD) is associated with matrix changes, biochemical changes, and inflammatory markers like interleukin-1 beta (IL-1ß). However, the exact mechanism remains unknown. This study aimed to investigate the role of IL-1ß, matrix metalloproteinase (MMP)-2, MMP-9, smooth muscle cell apoptosis, and elastic fibre fracture in the development of TAD in a rat model. METHODS: The TAD rat model was induced by ß-aminopropionitrile (BAPN). TAD was investigated in 112 male Sprague-Dawley rats, which were equally divided into four groups of 28 rats (Control, BAPN, BAPN + IL-1ß, and BAPN + IL-1ß antibody). Systolic blood pressure, survival, and the development of TAD were measured after six weeks. Expression of IL-1ß, MMP-2, and MMP-9 was measured by Western blot. Apoptosis, aortic elastin concentration, and biomechanical characteristics were measured by the TdT mediated dUTP nick end labelling assay, Victoria blue staining, and in vitro testing. RESULTS: During six weeks, the mortality was 0% (0/28) in the control group, 53.6% (15/28) in the BAPN group (p < .001 compared with the control group), 75.0% (21/28) in the BAPN + IL-1ß group (p = .007 compared with the BAPN group), and 35.7% (10/28) in the BAPN + IL-1ß antibody group (p = .023 compared with BAPN group and p < .001 compared with the BAPN + IL-1ß group). IL-1ß treatment deteriorates BAPN induced mortality and aneurysm expansion, which were attenuated by anti-IL-1ß treatment. In BAPN + IL-1ß group, stress and strain parameters were decreased by 13.5%-53.5% and elastin content was decreased by 14%, and IL-1ß, MMP-2, and MMP-9 were expressed higher by 117%, 108%, and 75% when compared with the rats in the BAPN group. Contrarily, in the BAPN + IL-1ß antibody group, the above changes could be completely (strain, elastin content, and expression of MMP-2) or partly (elasticity modulus, stress, and expression of MMP-9) blocked by anti-IL-1ß treatment. CONCLUSION: IL-1ß plays a critical role in TAD formation by altering the expression of MMP-2 and MMP-9, degrading the aortic wall matrix, causing elastic fibre rupture, and changing the stress or strain of the aortic wall. Anti-IL-1ß reduces the later effects and could be one of the molecular targets for prognosis and drug treatment of TAD in the future.

Off-the-Shelf Devices for Treatment of Thoracic Aortic Diseases: Midterm Follow-up of TEVAR With Chimneys or Physician-Made Fenestrations.

Purpose: To evaluate the midterm outcomes of thoracic endovascular aortic repair (TEVAR) using chimney grafts (ch-TEVAR) or thoracic stent-grafts with fenestrations made on the back table (f-TEVAR) to treat thoracic aortic dissection (TAD) and thoracic aortic aneurysm (TAA). Materials and Methods: A retrospective analysis was conducted of 474 consecutive patients (mean age 62.3±10.7 years; 346 men) treated with either f-TEVAR (n=110) or ch-TEVAR (n=364) for 352 TADs (81 f-TEVAR and 271 ch-TEVAR) or 122 TAAs (29 f-TEVAR and 93 ch-TEVAR) from 2008 to 2016. The primary endpoints at 30 days and during follow-up were overall mortality, aorta-related mortality, and major complications. The secondary endpoints were endoleak and reintervention. The patency of the target branches, cost of hospitalization, and the use of antiplatelet drugs were also analyzed. Results: Intraoperative type I endoleaks were treated in 69 (14.6%) cases (4 f-TEVAR and 65 ch-TEVAR, p<0.01) to achieve 100% technical success. Four (0.8%) patients died within 30 days [1 (0.9%) f-TEVAR and 3 (0.8%) ch-TEVAR]. Perioperative cerebral ischemia (1 fatal stroke) occurred in 9 (1.9%) patients: (1 f-TEVAR and 8 ch-TEVAR, p=0.39). During the mean follow-up of 50.6±20.0 months (49.5±18.3 months in f-TEVAR and 50.9±20.6 months in ch-TEVAR), 11 (2.3%) patients died of an aorta-related event. Type I endoleak was present in 40 (8.4%) patients (1 f-TEVAR and 39 ch-TEVAR, p<0.01). Eleven (2.3%) patients experienced stent-graft migration and 13 (2.7%) had a retrograde dissection. One hundred (16.9%) of the 593 branch stents occluded (4/75 in the f-TEVAR group and 96/518 in the ch-TEVAR group, p<0.01). The branch reintervention rate was 7.2% (34/474). The f-TEVAR group had a significantly higher probability of freedom from branch occlusion (92%) than the ch-TEVAR group (83%, p=0.007). Conclusion: Off-the-shelf techniques employing chimney grafts and homemade fenestrations are both suitable options for TAD and TAA involving the supra-aortic branches, with a low incidence of reintervention. Fenestrated TEVAR seems to have more favorable short- and midterm outcomes. Further study of these off-the-shelf techniques for aortic arch repair is warranted.

Long-term outcome of sac filling with fibrin sealant after endovascular aneurysm repair of abdominal aortic aneurysm with challenging aortic neck anatomy.

OBJECTIVE: A retrospective single-center study is reported here to assess the safety and long-term effectiveness of applying a fibrin sealant (FS) sac-filling strategy to eliminate type IA endoleak (TIAE) after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysm. METHODS: Characteristics of abdominal aortic aneurysm patients who had challenging proximal aortic neck anatomy (short or angulated) and underwent FS sac filling to resolve TIAE after traditional EVAR in Changhai Hospital between December 2006 and July 2010 were collected and reviewed. Intrasac pressure was measured with a preloaded catheter before and after FS filling to observe the immediate curative effect. The 7- to 10-year long-term effect was evaluated on the basis of the occurrence of endoleak, maximum aneurysm diameter, all-cause mortality, and other severe complications by annual aortic computed tomography angiography check. RESULTS: There were 107 patients with short (≤15 mm; 83/107 [77.6%]) or angulated (>60 degrees; 27/107 [25.2%]) aneurysm neck who underwent FS sac filling. The mean age of the patients was 71.1 ± 12.1 years (68 male patients). Of the 107 endoleaks, 106 (106/107 [99.1%]) were resolved, and 3 (3/107 [2.8%]) patients died in the perioperative period. Intrasac systolic, diastolic, mean, and pulse pressures decreased significantly in the treated cases (systolic pressure, 114.1 ± 16.7 mm Hg vs 59.5 ± 20.4 mm Hg; diastolic pressure, 65.0 ± 10.4 mm Hg vs 51.4 ± 18.2 mm Hg; mean pressure, 81.3 ± 11.4 mm Hg vs 54.1 ± 18.8 mm Hg; pulse pressure, 49.1 ± 12.8 mm Hg vs 8.2 ± 5.2 mm Hg; P < .01). During a median follow-up period of 89.1 months, the mean maximum aneurysm diameter became significantly smaller than that observed before the operation (53.23 ± 10.9 mm vs 59.86 ± 11.77 mm). The postoperative maximum aneurysm diameter decreased in 76 patients and was stable in 22 patients. One patient with aneurysm enlargement was transferred to open surgery because of a type IV endoleak, and another patient with no blood flow into the aneurysm sac observed by computed tomography angiography was closely followed up. Four patients received repeated endovascular treatment after the occurrence of type IB endoleak and aneurysm enlargement. After a median follow-up of 89.1 months, the cumulative survival rate was 90.7%, 80.4%, 72.0%, 58.9%, and 51.4% after 1 year, 3 years, 6 years, 8 years, and 10 years after the operation, respectively. There was no recurrent type I endoleak, distal embolization, migration, kinking, or malfunction after FS injections during the perioperative period and follow-up. CONCLUSIONS: FS sac filling combined with intrasac pressure measurement is a simple and effective treatment method to eliminate TIAE after EVAR, especially for patients with challenging proximal neck anatomy. This method could expand the current indications of EVAR.

Local upregulation of interleukin-1 beta in aortic dissecting aneurysm: correlation with matrix metalloproteinase-2, 9 expression and biomechanical decrease.

OBJECTIVES: Our goal was to examine whether interleukin-1 beta (IL-1ß) originates locally and its possible relationship with matrix metalloproteinases (MMPs), apoptosis, elastin fibres and biomechanics in aortic dissecting aneurysms (DAs). METHODS: Aortic DAs were induced in 24 rats with ß-aminopropionitrile (BAPN); another 12 rats without BAPN were designated as controls. Then IL-1ß levels were measured both in the circulation and in local aortic specimens. The expression of MMP-2 and MMP-9 and Victoria blue and TUNEL staining were also detected. Biomechanical parameters such as the elasticity modulus were used to detect the biomechanical changes in the aortic wall. The correlation of IL-1ß, MMP-2, MMP-9, apoptosis and biomechanical properties was analysed. RESULTS: Seventeen rats (17/24, 71%) in the BAPN-treated group died of DA rupture. IL-1ß levels were dramatically increased in the DA specimens but not in the circulation. Victoria blue staining confirmed the formation of the DA and the reduction of elastin content after induction by BAPN. The extent of apoptosis in the aortic media was dramatically higher in rats with BAPN-induced DA than that in the control group and that in rats treated with BAPN but without DA. MMP-2 and MMP-9 levels were significantly increased in BAPN-treated rats compared to the controls, but no statistical significance was found between rats with and without DA. There were significant differences in biomechanical parameters, such as the elasticity modulus. Among the 3 groups, IL-1ß was positively correlated with MMP-2 and MMP-9 levels and with the elasticity modulus but not with apoptosis. CONCLUSIONS: Local IL-1ß might participate in the formation of aortic DA through the upregulation of MMP-2 and MMP-9 and the breakage of elastin fibres, which finally weakens the biomechanical properties of the aortic wall.

D-dimer as a biomarker for acute aortic dissection: a systematic review and meta-analysis.

To perform a meta-analysis and examine the use of D-dimer levels for diagnosing acute aortic dissection (AAD). Medline, Cochrane, EMBASE, and Google Scholar were searched until April 23, 2014, using the following search terms: biomarker, acute aortic dissection, diagnosis, and D-dimer. Inclusion criteria were diagnosis of acute aortic dissection, D-dimer levels obtained, 2-armed study. Outcome measures were the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of D-dimer level for the diagnosis of AAD. Sensitivity analysis was performed using the leave-one-out approach. Of 34 articles identified, 5 met the inclusion criteria and were included in the analysis. The age of participants was similar between treatments within studies. The number of AAD patients ranged from 16 to 107 (total = 274), and the number of control group patients ranged from 32 to 206 (total = 469). The pooled sensitivity of D-dimer levels in AAD patients was 94.5% (95% confidence interval [CI] 78.1%-98.8%, P < 0.001), and the specificity was 69.1% (95% CI 43.7%-86.5%, P = 0.136). The pooled area under the receiver-operating characteristic curve for D-dimer levels in AAD patients was 0.916 (95% CI 0.863-0.970, P < 0.001). The direction and magnitude of the combined estimates did not change markedly with the exclusion of individual studies, indicating the meta-analysis had good reliability. D-dimer levels are best used for ruling out AAD in patients with low likelihood of the disease.

Combined endovenous laser therapy and pinhole high ligation in the treatment of symptomatic great saphenous varicose veins.

BACKGROUND: The aim of this study was to determine the effectiveness and short-term outcomes of endovenous laser therapy (EVLT) combined with pinhole high ligation (PHL) in the treatment of great saphenous varicose veins. METHODS: From February 2011 to May 2012, 200 patients with great saphenous varicose veins were treated using combined EVLT and PHL. Sixty-eight of them had concurrent TriVex suction. There were 118 men and 82 women with a median age of 61 (range 28-82) years. All patients had more than one of the following presentations, including lower extremity heaviness, pain, edema, varicose vein, skin changes, or ulceration. Based on the CEAP clinical classification, 20 patients had C2, 85 had C3, 48 had C4, 23 had C5, and 24 had C6 chronic venous disease. Ninety patients had VV involving the left lower extremity, 56 involving the right lower extremity, and 54 involving the bilateral lower extremities. Duplex ultrasound (US) was performed for all the 200 patients, and showed great saphenous valve dysfunction and reflux in 148 patients. Fifty-two of the 200 patients had concurrent mild femoral vein reflux. Deep venous thrombosis (DVT) was ruled out in all the patients. RESULTS: Technical success rate of PHL and laser ablation was 100%. Median follow-up was 9 months, ranging from 3 to 20 months. Symptoms were resolved or significantly improved in all patients after surgery. The ulcers healed in 23 of the 24 patients (96%) within 3 months. Ten patients developed subcutaneous hematoma, and 8 had slightly worsening edema. Ten patients with complications of numbness due to saphenous nerve burning injury were treated with mecobalamin, and the numbness sensation improved within 1 month and disappeared within 3 months. Nine patients sustained saphenous vein thrombophlebitis postoperatively and were treated with ibuprofen and a heating pad. There was no recanalization of the great saphenous vein, deep venous thrombosis (DVT), or deaths in this group of patients. CONCLUSIONS: Combined EVLT and PHL are less invasive and are effective in the treatment of symptomatic great saphenous varicose veins. PHL prevents DVT, and significantly decreases recanalization of the great saphenous vein after endovenous laser ablation. Short-term outcomes have been satisfactory, but long-term follow-up is needed.

Endovascular stent placement for treatment of spontaneous isolated dissection of the superior mesenteric artery.

BACKGROUND: Spontaneous isolated dissection of the superior mesenteric artery (SIDSMA) is a rare condition often associated with a poor prognosis. The goal of this study is to assess the efficacy of endovascular treatment of SIDSMA with stenting and investigate the possible therapeutic mechanisms involved. METHODS: This is a retrospective review of all patients undergoing endovascular treatment of SIDSMA from January 2009 to December 2011. Patient demographics, history, clinical presentation, laboratory tests, image characteristics, endovascular treatments, and follow-up outcome were analyzed. RESULTS: Twenty-four patients with symptoms were treated. All except 1 patient (23 of 24, 96%) underwent successful stent placement (16 with single stent and 7 with overlapping stents). A total of 30 stents (4 balloon-expanded and 26 self-expanding) were placed during the procedures. In the perioperative period and during follow-up, symptom relief was achieved in 20 (83%) patients, and abdominal pain remained unchanged in 4 (17%). No death or serious complications occurred. The median length of hospital stay and follow-up was 3.25 ± 2.23 days (range 2-7 days) and 13.15 ± 8.27 months (range 6-23 months), respectively. Computed tomography angiography (CTA) performed 6 months postoperatively revealed stent patency in 23 cases (100%), false lumen patency in 5 cases (22%), and new development of dissection in the SMA distal to the stent in 1 case (4%). No significant differences were observed in the incidence of false lumen patency between patients treated with a single stent and those treated with overlapping stents, and between patients with and without symptom relief (P > 0.05 for both). CONCLUSIONS: For symptomatic SIDSMA patients without intra-abdominal hemorrhage and intestinal infarction, endovascular stent placement is a feasible treatment choice with a high success rate and good clinical outcome. Overlapping stenting may be proposed for patients with aneurysmal dilation. False lumen patency may occur in some cases during follow-up, but it does not affect improvement of SIDSMA symptoms.

Endovascular management of pararenal aortic aneurysms with multiple overlapping uncovered stents.

OBJECTIVE: This study aims at evaluating the safety and efficacy of a porous stent system consisting of multiple overlapping uncovered stents in the treatment of complex aortic aneurysms with vital branches. METHODS: Data of all patients with aortic aneurysms treated in our center with multiple overlapping uncovered stents between February 2010 and December 2011 were retrospectively reviewed. Preoperative characteristics, intraoperative details, and follow-up outcomes were documented. Technical success was defined as successful deployment of the stents to target locations without procedure-related complications. Clinical success was characterized by complete shrinkage or stabilization of the aneurysm, preservation of vital branches, and absence of major complications. Patients were grouped, according to rapidity of aneurysm thrombosis, into fast-thrombosis group (complete thrombosis of aneurysmal sac was achieved in ≤6 months) and a delayed-thrombosis group (>6 months required for complete thrombosis). Possible factors affecting the speed of thrombosis were analyzed statistically with the Fisher exact test and the t-test. RESULTS: This porous stent system was used to treat 34 patients (23 men, 11 women; mean age, 65.7 years). Technical success was achieved in all patients (100%). Regular follow-up over 6 months was achieved in 29 patients (mean length of follow-up, 11.4 months). Complete thrombosis of the aneurysm sac within 12 months was observed in 24 patients (83%). Aneurysm shrinkage was documented in seven patients (24%) and stabilization in 21 (72%). All branch arteries covered by bare stents stayed patent during follow-up. The overall clinical success rate reached 97% in the follow-up group. Risk factors for delayed thrombosis included fewer stents implanted (P = .013), longer sac entrance (P = .043), and use of antiplatelet medication (P = .040). CONCLUSIONS: An alternative method of management of complicated aortic aneurysm appears to be feasible using overlapping bare stents, which may prevent aneurysm growth while preserving vital branches. The short-term outcome of our study seems encouraging but is not sufficient to draw a robust conclusion. Further hemodynamic and clinical studies are warranted to evaluate long-term efficacy.

A novel pressure difference-induced perforation aortic stent-grafts system: an experimental study.

BACKGROUND: Most of endovascular stent-graft modifications to preserve side branch must be customized according to extensive pre-operative assessment, which may not be possible in many hospitals and emergency settings. The study was to develop a novel stent-grafts system that would allow in situ "fenestration", with less reliance on preoperative imaging. METHODS: The magnitude of pressure difference (PD) between left subclavian artery (LSA) and aortic arch were measured in 12 experimental pigs. Changes of PD before and after LSA was covered were analyzed respectively. The novel stent graft was made by multi-dimensional and multiple textiles forming technology. According to the PD measurement in pigs, we evaluated the feasibility of the stent-graft in a mock circulation system. RESULTS: In pigs, the blood pressure of aortic arch was significantly higher than that of LSA after it was covered (P < 0.001) and PD was (42.78 ± 5.17) mmHg. After target vessel was covered and when PD between the LSA and aorta reached the magnitude measured in pigs, contrast media oozed from the cranny of graft to the LSA, which was generated by sliding and deformation of yarns of novel stent-graft. CONCLUSIONS: The study proposes the design of pressure difference-induced perforation aortic stent-grafts system and verifies that the PD between LSA and aortic arch is high enough to allow in situ "fenestration" by stent graft made by multi-dimensional and multiple textiles forming technology.

Multiple overlapping bare stents for endovascular visceral aneurysm repair: a potential alternative endovascular strategy to multilayer stents.

BACKGROUND: Multilayer stent has become a new endovascular strategy for visceral artery aneurysm repair. However, its use was not allowed in some areas, such as China. This study evaluates an alternative method: multiple overlapping bare stents for repairing visceral artery aneurysms. METHODS: Twenty-four patients with celiac artery aneurysm (n = 2), splenic artery aneurysm (n = 8), hepatic artery aneurysm (n = 3), superior mesenteric artery aneurysm (n = 6), and renal artery aneurysm (n = 5) were treated with 2 to 4 overlapping bare stents. Long-term results, including clinical achievement ratio and target artery patency, were followed up with computed tomographic angiography. RESULTS: Insertion of overlapping bare stents was successful in all patients. Five aneurysms (21%) were totally excluded 3 months after operation, increasing to 12 (50%) and 20 (83%) aneurysms with total isolation at 6 and 12 months' follow-up, respectively. The clinical achievement ratios of multiple overlapping bare stents on splenic artery aneurysms, hepatic artery aneurysms, renal artery aneurysms, celiac artery aneurysms, and superior mesenteric artery aneurysms were 75%, 100%, 80%, 50%, and 100%, respectively. All cases combined had 100% target artery patency. CONCLUSIONS: Preliminary experience showed that repair using multiple overlapping bare stents seemed to be a potential alternative strategy for treating visceral artery aneurysm, resulting in target artery patency. However, the exact mechanism requires further study and more cases should be involved.

Comparison of ß-aminopropionitrile-induced aortic dissection model in rats by different administration and dosage.

This study compared three ß-aminopropionitrile (BAPN) treatment rats to find the optimal BAPN model for thoracic aortic dissection and aneurysm in one study. Sixty rats were divided into five groups: control, injected control, 0.25% and 0.4% BAPN treatment (orally), and 667 mg/kg/day BAPN injection subcutaneously. Incidence of aortic dissection and aneurysm, aortic weight and diameter were measured directly. Thickness of media and area of aorta were measured by hematoxylin and eosin and Victoria blue staining. The mortality, incidence of aortic dissection and the rupture rate of dissected aneurysm in 0.25% group was much higher than in the other two BAPN treatment groups. The diameter of thoracic aorta in 0.25% and the whole aorta in 0.4% group significantly increased. Media thickness and area of thoracic aorta were increased by 91% and 54% in 0.25% group, and by 17% and 12% in the BAPN injection group. Thickness and area were increased by 49% and 35% on thoracic aorta, and 29% and 46% on abdominal aorta in 0.4% group. In conclusion, 0.25%, 0.4% and BAPN injection groups might be appropriate for aortic dissection and pharmaceutical study, thoracic-abdominal aortic aneurysm or dilation and biomechanical research, respectively.

Multilayer stents, a new progress in the endovascular treatment of aneurysms.

OBJECTIVE: To review the recent progress of multilayer stents in treating arterial aneurysms and to draw an initial conclusion about its paradigm. DATA SOURCES: PubMed database and ELSEVIER database were searched with the keywords "cardiatis" or "multilayer stent" for relevant articles from January 2008 to September 2012. Relevant websites (provided by Cardiatis) were also involved in the review process. STUDY SELECTION: Well-controlled, relatively large-scale, retrospective studies as well as meaningful individual cases were all selected as materials. RESULTS: A total of 23 articles were involved in this review. The newly introduced Cardiatis multilayer stent aims at creating an active flow-modulating barrier between normal blood flow and aneurismal sac, which can induce thrombosis within aneurismal sac and preserve collateral circulation at the same time. Currently, it has been applied for complicated aneurysms located in different segments of the arterial system. CONCLUSION: This new concept of multilayer uncovered stent offers a promising alterative in the treatment of arterial aneurysms. However, a further large-scale clinical and hemodynamic study is required to evaluate the long-term effects.

Innovative sandwich technique in treating a symptomatic saccular suprarenal aneurysm involving the celiac trunk.

PURPOSE: To describe a new technique that combines traditional stent graft and multiple overlapping uncovered stents to form a sandwich-like structure in the management of a wide-necked saccular suprarenal aneurysm. CASE REPORT: An 83-year-old woman was admitted to the hospital with a large symptomatic aortic aneurysm that involved celiac trunk. Traditional stent graft and coiling were precluded due to the anatomical complexity of the aneurysm. A novel combination of multiple overlapping stents and grafted stents was utilized in this patient in order to maximally reduce the blood flow into the sac and to preserve visceral branches. At 3-month follow-up, patent celiac artery and superior mesenteric artery along with complete shrinkage of aneurismal sac were documented. CONCLUSION: The combination of grafted stents and uncovered stents can effectively reduce velocity and volume of blood flow into the aneurismal sac, which induces thrombosis within the sac, while all the branches could be preserved.

Dramatic decrease of aortic longitudinal elastic strength in a rat model of aortic dissection.

BACKGROUND: This study aimed to evaluate thoracic aortic longitudinal elastic strength in a rat model of aortic dissection (AD). METHODS: Young Sprague Dawley rats were fed 0.25% ß-aminopropionitrile (BAPN). Biomechanical and biochemistry properties of the aorta were analyzed. Elasticity modulus, maximum stretching length, draw ratio, maximum load, maximum strength, and maximum extensibility were measured. RESULTS: More than one-half of BAPN-treated rats (52.9%) died of aortic rupture secondary to AD during the experiment. The diameter of the aneurysms was 6.33 ± 1.17 mm and the length was 9.33 ± 4.95 mm. The maximum diameter was significantly increased in BAPN-treated rats with AD (group B2) compared with rats without AD (group B1) and control group (group A) (P = 0.001 and P < 0.001, respectively), but was not different between group B1 and group A (P = 0.108). Thickness of media and initial area in aorta of BAPN-treated rats were significantly increased compared with control group (P = 0.001 and P < 0.001, respectively), but no difference in initial area was observed between group B1 and group B2 (P = 0.54). Maximum stretching length, draw ratio, maximum load, maximum strength, maximum extensibility, and elasticity modulus were dramatically decreased in group B2 compared with group B1 and group A (group B2 vs. group B1: P < 0.001; group B1 vs. group A: P < 0.001). CONCLUSIONS: We successfully established a rat model of AD with a high incidence of rupture and mortality. Examinations of strain and stress parameters as well as elasticity modulus of the dissected and the nondissected aorta help understand pathogenesis of AD.

[Biomechanical properties study of aorta in ß-aminopropionitrile-induced rat model].

OBJECTIVE: To investigate thoracic aortic longitudinal elastic strength in ß-aminopropionitrile (BAPN) treated rat model of aortic dissection (AD). METHODS: Twenty-nine young rats (Sprague-Dawley) were divided into tow groups, control group (n = 12) and BAPN group (n = 17). Seventeen rats were treated with 0.25% BAPN mixed in feed for 6 weeks. All the rats were sacrificed in the end of experiment and aorta was harvested for biomechanical and pathological study. Longitudinal elastic strength and stress were detected and analyzed by material testing machine. Elasticity modulus as well as maximum stretching length, draw ratio, maximum load, maximum strength, and maximum extensibility was calculated according to the analysis with thickness and area of aortic media. RESULTS: Nine BAPN-treated rats died of aortic dissecting aneurysm rupture during the experiment. The diameter of the aneurysms was (6.33 ± 1.17) mm and the length was (9 ± 5) mm. The maximum diameter significantly increased in BAPN-induced rats with AD (group B2) compared with without AD (group B1) and control group ((6.49 ± 1.20) mm vs. (1.45 ± 0.11), (1.25 ± 0.26); F = 165.257, P = 0.001 and 0.000, respectively), but there was no significance between group B1 and control group (P = 0.108). Thickness and area of aortic media in BAPN-induced rats significantly increased compared with control group (F = 27.277 and 27.153, P = 0.000 and 0.000, respectively), but there was no significance of area between group B1 and B2 (P = 0.540). Maximum stretching length, draw ratio, maximum load, maximum strength maximum extensibility and elasticity modulus were significantly decreased from group B2, group B1 to control group (P < 0.01, respectively). CONCLUSIONS: This study built a successful model of AD. Biomechanical analysis and the decrease of maximum stretching length, draw ratio, maximum load, maximum strength maximum extensibility and elasticity modulus may explain the formation of AD partly.

[Efficacy of Chinese herbal medicine Mailuo Shutong Granule and Hirudoid cream for chronic venous disorder-induced pigmentation in lower extremities: a prospective, randomized controlled trial].

BACKGROUND: Chronic venous disorder (CVD) of the lower extremities generally induces dermatologic complications in lower extremity skin, such as hyperpigmentation. If not treated effectively, the lesions may develop into severe outcomes, including dermal ulcer or necrosis. OBJECTIVE: To evaluate the clinical efficacy of Mailuo Shutong Granule, a compound traditional Chinese herbal medicine, and Hirudoid cream (heparinoid), in treatment of patients with dermal hyperpigmentation of skin caused by CVD. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 108 CVD outpatients with pigmentation from Department of Vascular Surgery, Shanghai Changhai Hospital were randomly divided into Mailuo Shutong group, Hirudoid group and combined therapy group, with 36 patients in each group. Patients in the Mailuo Shutong group and the Hirudoid group were treated with Mailuo Shutong Granule or Hirudoid cream, respectively, while those in the combined therapy group were treated with Mailuo Shutong Granule plus Hirudoid cream. They were all treated for 28 d. MAIN OUTCOME MEASURES: Before and after the 28-day treatment, area and average gray value of pigmentation lesions were measured and evaluated. RESULTS: Thirty-three cases in the Mailuo Shutong group, 34 cases in the Hirudoid group and 31 cases in the combined therapy group were included for analysis. After treatment, area of pigmentation decreased and average gray value of pigmentation declined in all the 3 groups (P<0.05). The reductions of area and average gray value in the combined therapy group were more significant than those in the Mailuo Shutong group and Hirudoid group (P<0.05). There were no differences in improvement of pigmentation between the Mailuo Shutong group and Hirudoid group (P>0.05). CONCLUSION: These data suggest that both Mailuo Shutong Granule and Hirudoid cream can improve CVD-induced hyperpigmentation, and combined treatment of the two drugs results in better clinical efficacy.

Overexpression of interleukin-1ß and interferon-γ in type I thoracic aortic dissections and ascending thoracic aortic aneurysms: possible correlation with matrix metalloproteinase-9 expression and apoptosis of aortic media cells.

OBJECTIVE: To examine the expression of interleukin-1ß and interferon-γ and their possible roles in aortic dissections and aneurysms. METHODS: Aortic specimens were obtained from patients with type I thoracic aortic dissection, ascending thoracic aortic aneurysms, and control organ donors. The expression of interleukin-1ß, interferon-γ, matrix metalloproteinase-9, and signal transduction factors phospho-p38 and phosphorylated c-jun N-terminal kinase (phospho-JNK) were detected by real time reverse transcription-polymerase chain reaction (real time RT-PCR), Western blot, and immunohistochemistry, respectively. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining was performed to detect apoptosis of media cells. The correlation of these factors and apoptosis was also studied. RESULTS: Apoptosis in the media of thoracic aortic dissection and in ascending thoracic aortic aneurysms was dramatically higher than in the control group. The expression of interleukin-1ß gradually increased from the control group, thoracic aortic dissection to ascending thoracic aortic aneurysms (p < 0.01, respectively). The expression of interferon-γ and matrix metalloproteinase-9 was significantly increased in the media of thoracic aortic dissection and ascending thoracic aortic aneurysms compared with the control group (p < 0.01, respectively). There were positive correlations between interleukin-1ß versus matrix metalloproteinase-9, interleukin-1ß versus phospho-p38 in thoracic aortic dissection (p < 0.01, respectively), and interferon-γ versus matrix metalloproteinase-9, interferon-γ versus phospho-JNK, interferon-γ versus apoptosis, and interleukin-1ß versus apoptosis in ascending thoracic aortic aneurysms (p = 0.02, 0.02, p < 0.01, p < 0.01). CONCLUSIONS: Interleukin-1ß and interferon-γ might effect the formation of thoracic aortic dissection and ascending thoracic aortic aneurysms possibly through the up-regulation of matrix metalloproteinase-9 and the apoptosis of media cells in humans.

A novel strategy for development of glucocorticoids through non-genomic mechanism.

Glucocorticoids (GCs) are routinely believed to take effect through genomic mechanisms, which are also largely responsible for GCs' side effects. Beneficial non-genomic effects of GCs have been reported as being independent of the genomic pathway. Here, we synthesized a new type of GCs, which took effect mainly via non-genomic mechanisms. Hydrocortisone was conjugated with glycine, lysine and phenylalanine to get a bigger molecular structure, which could hardly go through the cell membrane. Evaluation of the anti-inflammatory efficacy showed that hydrocortisone-conjugated glycine (HG) and lysine could inhibit neutrophil degranulation within 15 min. HG could inhibit IgE-mediated histamine release from mast cells via a non-genomic pathway, and rapidly alleviate allergic reaction. Luciferase reporter assay showed that HG would not activate the glucocorticoid response element within 30 min, which verified the rapid effects independent of the genomic pathway. The work proposes a novel insight into the development of novel GCs, and provides new tools for experimental study on non-genomic mechanisms.

[Fibrin glue embolization treating intra-operative type I endoleak of endovascular repair of abdominal aortic aneurysm: long-term result].

OBJECTIVES: To analyze the long-term results of fibrin glue embolization to eliminate type I endoleaks after endovascular aneurysm repair (EVAR), and to assess the feasibility and durability of this technique. METHODS: From August 2002 to June 2010, among the 953 EVAR patients, 51 (5.4%) patients underwent intraoperative transcatheter fibrin glue sac embolization to resolve type I endoleak persisting after initial intraoperative maneuvers to close the leak or in necks too short or angulated for cuff placement. Computed tomographic angiography was performed to assess the outcome after 3, 6, and 12 months and annually thereafter. A retrospective study was conducted, and characteristics of the patients, intra-sac pressure, hospital course, and long-term outcomes were recorded. RESULTS: Among the 51 patients, 19 (37.3%) patients had proximal necks long < 10 mm, and 6 (11.8%) patients had proximal neck angulation > 60°; 22 patients (3 additional iliac extension, 14 cuffs, and/or 8 stents) had been placed with additional devices. After fibrin glue injection, 50 (98.0%) of the 51 endoleaks were successfully resolved, and intra-sac pressure (including systolic, diastolic, mean pressures, pulse pressure, and the mean pressure indexes) decreased significantly in these cases. The patient who failed embolotherapy was converted to open surgery (2.0%); he died 2 months later from multiorgan failure. And other two (4.8%) patients died in the peri-operative period from myocardial infarction. The median of follow-up of 48 patients was 45 months (range 4 - 106 months). The mean maximal aneurysm diameter fell from the baseline (61.5 ± 15.2) mm to (48.8 ± 10.1) mm (P = 0.000). Three (6.2%) patients died in the follow-up duration (1 aneurysm-related, died of renal failure which was caused by the compromised renal artery). Cumulative survival was 97.9% at 1 year, 94.5% at 3 years, and 90.8% at 4 years. No recurrent type I endoleak or glue-related complications were observed in follow-up. CONCLUSIONS: Fibrin glue embolization to eliminate type I endoleak after EVAR has yielded promising results in this study, and it can effectively and durable resolve the type I endoleaks. Balloon occlusion of the inflow of the endoleak must be done during glue injection, to enhance the safety and facilitate formation of a structured fibrin clot.