Radiation diagnosis of abdominal aortic aneurysms

Four hundred and forty seven patients with aneurysms of the abdominal aorta (AAA), including 238 patients with aneurysmal rupture, were admitted to the Research Institute of Emergency Care in 1990 to 2000. The results of studies in 225 patients (ultrasonography in 197, computed tomography in 59, and angiography in 104), including 155 patients with aneurysmal rupture were analyzed. Computed tomography (CT) has proved to be the most accurate technique in the detection and estimation of the size of aneurysms, as well as in the identification of ruptures (83.9%) and inferior to angiography (AG) in the study of involvement of the branches of the abdominal aorta. Ultrasound study (US) ranks below CT in its accuracy (US detects ruptures in 67.8%); however, US surpasses CT and AS in screening, particularly valuable at an admission unit and an intensive care unit, which permits repeated studies. AG has turned out to be the most valid method in identifying the involvement of renal and iliac arteries in aneurysm and in detecting aortocaval anastomoses; yet it is inferior to US and CT (the former revealed rupture and dissection in 18.6% of cases) in solving other diagnostic tasks. Based on the analysis, the optimal sequence of studies in the patients is US, CT, and AG.     

Extracellular matrix composition and remodeling in human abdominal aortic aneurysms: a proteomics approach

Abdominal aortic aneurysms (AAA) are characterized by pathological remodeling of the aortic extracellular matrix (ECM). However, besides the well-characterized elastolysis and collagenolysis little is known about changes in other ECM proteins. Previous proteomics studies on AAA focused on cellular changes without emphasis on the ECM. In the present study, ECM proteins and their degradation products were selectively extracted from aneurysmal and control aortas using a solubility-based subfractionation methodology and analyzed by gel-liquid chromatography-tandem MS and label-free quantitation. The proteomics analysis revealed novel changes in the ECM of AAA, including increased expression as well as degradation of collagen XII, thrombospondin 2, aortic carboxypeptidase-like protein, periostin, fibronectin and tenascin. Proteomics also confirmed the accumulation of macrophage metalloelastase (MMP-12). Incubation of control aortic tissue with recombinant MMP-12 resulted in the extensive fragmentation of these glycoproteins, most of which are novel substrates of MMP-12. In conclusion, our proteomics methodology allowed the first detailed analysis of the ECM in AAA and identified markers of pathological ECM remodeling related to MMP-12 activity.     

Porohyperelastic finite element modeling of abdominal aortic aneurysms

Abdominal aortic aneurysm (AAA) is the gradual weakening and dilation of the infrarenal aorta. This disease is progressive, asymptomatic, and can eventually lead to rupture--a catastrophic event leading to massive internal bleeding and possibly death. The mechanical environment present in AAA is currently thought to be important in disease initiation, progression, and diagnosis. In this study, we utilize porohyperelastic (PHE) finite element models (FEMs) to investigate how such modeling can be used to better understand the local biomechanical environment in AAA. A 3D hypothetical AAA was constructed with a preferential anterior bulge assuming both the intraluminal thrombus (ILT) and the AAA wall act as porous materials. A parametric study was performed to investigate how physiologically meaningful variations in AAA wall and ILT hydraulic permeabilities affect luminal interstitial fluid velocities and wall stresses within an AAA. A corresponding hyperelastic (HE) simulation was also run in order to be able to compare stress values between PHE and HE simulations. The effect of AAA size on local interstitial fluid velocity was also investigated by simulating maximum diameters (5.5 cm, 4.5 cm, and 3.5 cm) at the baseline values of ILT and AAA wall permeability. Finally, a cyclic PHE simulation was utilized to study the variation in local fluid velocities as a result of a physiologic pulsatile blood pressure. While the ILT hydraulic permeability was found to have minimal affect on interstitial velocities, our simulations demonstrated a 28% increase and a 20% decrease in luminal interstitial fluid velocity as a result of a 1 standard deviation increase and decrease in AAA wall hydraulic permeability, respectively. Peak interstitial velocities in all simulations occurred on the luminal surface adjacent to the region of maximum diameter. These values increased with increasing AAA size. PHE simulations resulted in 19.4%, 40.1%, and 81.0% increases in peak maximum principal wall stresses in comparison to HE simulations for maximum diameters of 35 mm, 45 mm, and 55 mm, respectively. The pulsatile AAA PHE FEM demonstrated a complex interstitial fluid velocity field the direction of which alternated in to and out of the luminal layer of the ILT. The biomechanical environment within both the aneurysmal wall and the ILT is involved in AAA pathogenesis and rupture. Assuming these tissues to be porohyperelastic materials may provide additional insight into the complex solid and fluid forces acting on the cells responsible for aneurysmal remodeling and weakening.     

HOXA4 protein levels and localization in the aorta and in human abdominal aortic aneurysms

This report presents evidence for the specificities of select commercially available HOXA4 antibodies in regards to concerns about the specificity of the HOXA4 antibody used by Lillvis et al. (Regional expression of HOXA4 along the aorta and its potential role in human abdominal aortic aneurysms. BMC Physiol 2011, 11:9). Using an antibody characterized extensively by us, Lillvis et al. report detecting HOXA4 at a size of 33 kDa despite our previous reports that HOXA4 is detected at ~37-39 kDa and that the ~30-33 kDa band is non-specific. Using small interfering RNA targeting HOXA4, forced expression of full-length HOXA4 and HOXA4-positive and -negative ovarian cancer cell lines, we confirm our previous findings that the ~30-33 kDa band is non-specific and that HOXA4 is detected at ~37-39 kDa. Moreover, we demonstrate that HOXA4 small interfering RNA reduces the ~37-39 kDa HOXA4 band, but not the ~30-33 kDa non-specific band, in a human acute monocytic leukemia cell line used by Lillvis et al. Western blot analysis performed with two additional commercially available HOXA4 antibodies also detected HOXA4 at ~37-39 kDa. Lastly, immunofluorescent staining of a HOXA4-negative ovarian cancer cell line with the antibody used by Lillvis et al. yields strong perinuclear staining, similar to that observed by Lillvis et al., which cannot be attributed to HOXA4. Our results highlight and briefly discuss the importance of careful antibody validation and selection for use in various applications.     

Variations of dissection properties and mass fractions with thrombus age in human abdominal aortic aneurysms

Introduction

Thrombus ages, defined as four relative age phases, are related to different compositions of the intraluminal thrombus (ILT) in the abdominal aortic aneurysm (AAA) (Tong et al., 2011b). Experimental studies indicate a correlation between the relative thrombus age and the strength of the thrombus-covered wall.

Methods

On 32 AAA samples we performed peeling tests with the aim to dissect the material (i) through the ILT thickness, (ii) within the individual ILT layers and (iii) within the aneurysm wall underneath the thrombus by using two extension rates (1 mm/min, 1 mm/s). Histological investigations and mass fraction analysis were performed to characterize the dissected morphology, to determine the relative thrombus age, and to quantify dry weight percentages of elastin and collagen in the AAA wall.

Results

A remarkably lower dissection energy was needed to dissect within the individual ILT layers and through the thicknesses of old thrombi. With increasing ILT age the dissection energy of the underlying intima–media composite continuously decreased and the anisotropic dissection properties for that composite vanished. The quantified dissection properties were rate dependent for both tissue types (ILT and wall). Histology showed that single fibrin fibers or smaller protein clots within the ILT generate smooth dissected surfaces during the peeling. There was a notable decrease in mass fraction of elastin within the thrombus-covered intima–media composite with ILT age, whereas no significant change was found for that of collagen.

Conclusions

These findings suggest that intraluminal thrombus aging leads to a higher propensity of dissection for the ILT and the intima–media composite of the aneurysmal wall.     

Computed tomography in the diagnosis of complicated abdominal aortic aneurysms

The paper analyzes the results of computed tomography (CT) conducted in 54 patients with complicated abdominal aortic aneurysms (AAA). Of them, 37 cases were diagnosed as having a complete rupture. There was dissection of the wall of the aneurysmally altered aorta and its slight tear in 11 and 6 cases, respectively. CT has been shown to allow one to diagnose complications due to AAA, their pattern, and site, to identify the factors that increase a risk for rupture, such as a slight tear of the inner layers of the wall of the aneurysmal abdominal aorta and its wall dissection. This all assists in solving a variety of the problems associated with treatment policy and may substantially reduce postoperative morbidity in this group of patients.     

Pravastatin increases the expression of the tissue inhibitor of matrix metalloproteinase-1 and the oncogene Bax in human aortic abdominal aneurysms

The effect of pravastatin on matrix metalloproteinase-9 (MMP-9) and the level of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 was studied in explants of human abdominal aortic aneurysm (AAA) obtained from 13 patients. The effect of pravastatin on the apoptotic status of human AAA explants was also examined. Total MMP-9 content did not differ in human AAA explants incubated in vitro in the presence or absence of pravastatin (10-6 mol/L) for 48 h. TIMP-1 levels were significantly increased in pravastatin-incubated AAA explants, but TIMP-2 production was not modified by pravastatin. Western blot experiments showed that, whereas Bax expression was increased in pravastatin-incubated AAA explants, the expression of Bcl-2 was not modified. On the other hand, the ratio of the expression of Bax to Bcl-2, an apoptotic index, was not modified by pravastatin. In the human AAA explants, the increase in Bax expression, but not the increase in TIMP-1 expression elicited by pravastatin, was reversed by L-mevalonate, a downstream HMG-CoA reductase metabolite, suggesting that the expression of Bax and TIMP-1 followed HMG-CoA reductase-dependent and -independent pathways, respectively. In conclusion, pravastatin increases both TIMP-1 and Bax expression in human AAA explants without changes in either MMP-9 activity or the apoptotic status.     

Blood flow in abdominal aortic aneurysms: pulsatile flow hemodynamics

Numerical predictions of blood flow patterns and hemodynamic stresses in Abdominal Aortic Aneurysms (AAAs) are performed in a two-aneurysm, axisymmetric, rigid wall model using the spectral element method. Physiologically realistic aortic blood flow is simulated under pulsatile conditions for the range of time-averaged Reynolds numbers 50< or =Re(m)< or =300, corresponding to a range of peak Reynolds numbers 262.5< or =Re(peak) < or = 1575. The vortex dynamics induced by pulsatile flow in AAAs is characterized by a sequence of five different flow phases in one period of the flow cycle. Hemodynamic disturbance is evaluated for a modified set of indicator functions, which include wall pressure (p(w)), wall shear stress (tau(w)), and Wall Shear Stress Gradient (WSSG). At peak flow, the highest shear stress and WSSG levels are obtained downstream of both aneurysms, in a pattern similar to that of steady flow. Maximum values of wall shear stresses and wall shear stress gradients obtained at peak flow are evaluated as a function of the time-average Reynolds number resulting in a fourth order polynomial correlation. A comparison between predictions for steady and pulsatile flow is presented, illustrating the importance of considering time-dependent flow for the evaluation of hemodynamic indicators.     

Indications for surgical treatment of abdominal aortic aneurysms]

The results of the surgical treatment of 115 patients with the abdominal aortal aneurysms are presented. Indications to surgery depending on the stage of aneurysm, way of classification, and coexisting cardiological disorders have been discussed. Excellent and favorable results of surgery have been achieved in 70 patients (60.9%). Overall hospital mortality rate was 39.1%. Out of patients who underwent elective surgery 11.6% died, in the group operated urgently--43.3%, and in emergency situation 89.4% of the operated patients died. Percentage of patients with coexisting cardiological disorders amounted to 54%, 62%, and 80% respectively. A strict correlation of the results of surgery and duration of the disease, and consequently classification to the treatment, has been noted. Indications to the elective surgery are related to the size of aneurysm, rate of its enlargement, patient's age, and general health.     

Diagnosis and management of 528 abdominal aortic aneurysms.

Between 1960 and 1979 528 patients with abdominal aortic aneurysms presented to the university department of surgery. Of these, 222 (42%) were elective cases, 72 acute (14%), 174 had ruptured (33%), and four had had a spontaneous aortoduodenal fistula (1%). In all these patients resections were undertaken, but in another 56 patients (11%) the aneurysm was not resected. A review of these cases showed that 91% had symptoms at their first presentation; abdominal pain and backache being most common. The diagnosis could be established in 91% by the presence of pulsatile abdominal mass on clinical examination. The operative mortality for elective resection was 8%, for acute 19%, for ruptured cases 42%, and for spontaneous aortoduodenal fistula 50%. After successful resection the overall five-year survival was 65% by the life table method, and there was no significant difference between elective, acute, and ruptured cases. This five-year survival after resection compares favourably with the expected 76% survival of a similar normal population, and was considerably better than that for conservatively treated patients. As most cases have symptoms, and diagnosis may be established easily by routine physical examination in 91%, the prognosis for this condition could be considerably improved by increased awareness of its existence and early referral for treatment as an elective surgical procedure.