Expression of TGF-β1 and β3 but not apoptosis factors relates to flow-induced aortic enlargement

BACKGROUND: Cell proliferation and apoptosis are both involved in arterial wall remodeling. Increase in blood flow induces arterial enlargement. The molecular basis of flow-induced remodeling in large elastic arteries is largely unknown. METHODS: An aortocaval fistula (ACF) model in rats was used to induce enlargement in the abdominal aorta. Aortic gene expression of transforming growth factors beta (TGF-β) and apoptosis-related factors was assessed at 1 and 3 days and 1, 2, 4, and 8 weeks. Expression levels were determined using a ribonuclease protection assay and western blotting. Cell proliferation and apoptosis were analyzed using BrdU incorporation and TUNEL techniques. RESULTS: Blood flow increased 5-fold immediately after ACF (P<0.05). Lumen diameter of the aorta was 30% and 75% larger at 2 and 8 weeks respectively than those of controls (P<0.05). mRNA levels of TGF-β1 and TGF-β3 increased after ACF, peaked at 3 days (P<0.05) and returned to normal level at 1 week and thereafter. Western blotting showed enhanced expression of TGF-β1 at 3 days and TGF-β3 at 1 and 3 days and 1 week (P<0.05). mRNA levels of Bcl-xS initially decreased at 1 day, 3 days and 1 week, followed a return to baseline level at 2 weeks. Cell proliferation was observed at all time points after ACF (P<0.001 vs. controls) with proliferation in endothelial cells more significant than smooth muscle cells. Apoptosis was not significant. CONCLUSIONS: Gene expression of TGF-β1 and β3 precedes arterial enlargement. Expression of apoptosis related factors is little regulated in the early stage of the flow-induced arterial remodeling

Multidisciplinary approach to treat ruptured abdominal aortic aneurysm into the vena cava

Funding Information: The editors and reviewers of this article have no relevant financial relationships to disclose per the Journal policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.publishersversionPeer reviewe

Hypogastric artery bypass to preserve pelvic circulation: improved outcome after endovascular abdominal aortic aneurysm repair

AbstractObjectiveThis study was carried out to compare the functional outcomes after hypogastric artery bypass and coil embolization for management of common iliac artery aneurysms in the endovascular repair of aortoiliac aneurysms (EVAR).MethodsBetween 1996 and 2002, 265 patients underwent elective or emergent EVAR. Data were retrospectively reviewed for 21 (8%) patients with iliac artery aneurysms 25 mm or larger that involved the iliac bifurcation. Patients underwent hypogastric artery bypass (n = 9) or coil embolization (n = 12). Interviews about past and current levels of activity were conducted. A disability score (DS) was quantitatively graded on a discrete scale ranging from 0 to 10, corresponding to “virtually bed-bound” to exercise tolerance “greater than a mile.” Worsening or improvement of symptoms was expressed as a difference in DS between two time points (-, worsening; +, improvement).ResultsThere was no difference in age (72.6 ± 7.3 years vs 73.1 ± 6.4 years), sex (male-female ratio, 8:1 vs 11:1), abdominal aortic aneurysm size (60.1 ± 5.9 mm vs 59.3 ± 7.0 mm), or number of preoperative comorbid conditions (1.9 ± 0.8 vs 2.1 ± 0.8) between hypogastric bypass and coil embolization groups, respectively. Mean follow-up was shorter after hypogastric bypass (14.8 vs 20.5 months; P < .05). There was no difference in the mean overall baseline DS between the bypass and the embolization groups (8.0 vs 7.8). Six (50%) of the 12 patients with coil embolization reported symptoms of buttock claudication ipsilateral to the occluded hypogastric artery. No symptoms of buttock claudication were reported after hypogastric bypass (P < .05). There was a decrease in the DS after both procedures; however, coil embolization was associated with a significantly worse DS compared with hypogastric artery bypass (4.5 vs 7.3; P < .001). In 4 (67%) of 6 patients with claudication after coil embolization symptoms improved, with a DS of 5.4 at last follow-up. This was significantly worse than in patients undergoing hypogastric artery bypass, with a DS of 7.8 at last follow-up (P < .001). There was no difference between the groups in duration of procedure, blood loss, length of hospital stay, morbidity, or mortality (0%).ConclusionsHypogastric artery bypass to preserve pelvic circulation is safe, and significantly decreases the risk for buttock claudication. Preservation of pelvic circulation results in significant improvement in the ambulatory status of patients with common iliac artery aneurysms, compared with coil embolization

Rate of change in abdominal aortic aneurysm diameter after endovascular repair

AbstractObjective: Untreated abdominal aortic aneurysms (AAAs) enlarge at a mean rate of 3.9 mm/y with great individual variability. We sought to determine the effect of endovascular repair on the rate of change in aneurysm size. Methods: There were 110 patients who underwent endovascular AAA repair at Stanford University Medical Center and who were followed up for 1 to 30 months (mean, 10 months) with serial contrast-infused helical computed tomography (CT). Maximal aneurysm diameter was determined using two independent methods: (1) measured manually, from cross-sectional computed tomography (XSCT) angiograms and (2) calculated from quantitative three-dimensional computed tomography (3DCT) data as orthonormal diameter. Results: Maximal cross-sectional aneurysm diameter measured by hand (XSCT) and calculated as orthonormal values (3DCT) correlated closely (r = 0.915; P <.001). The XSCT-measured diameter was larger by 2.3 ± 3.75 mm (P <.001), and the 95% CI for SE of the bias was 1.85 to 2.75 mm. Preoperative aneurysm diameter (XSCT 59.1 ± 8.4 mm; 3DCT 58.1 ± 9.3 mm) did not differ significantly from the initial postoperative diameter. Considering all patients, XSCT diameter decreased at a rate of 0.34 ± 0.69 mm/mo, and 3DCT diameter decreased at a rate of 0.28 ± 0.79 mm/mo. Aneurysms in patients without endoleaks had a higher rate of decrease, an XSCT diameter by 0.50 ± 0.74 mm/mo, and 3DCT diameter by 0.46 ± 0.84 mm/mo. In these patients, mean absolute decrease in diameter at 6 months was 3.4 ± 4.5 mm (XSCT) and 3.3 ± 5.9 mm (3DCT) and at 12 months, 5.9 ± 5.7 mm (XSCT) and 5.4 ± 5.7 mm (3DCT). Aneurysms in patients with persistent endoleaks did not change in mean XSCT diameter, and 3DCT diameter increased by 0.12 ± 0.52 mm/mo (not significant). Aneurysm diameter remained within 4 mm of original size in 68% (3DCT) to 71% (XSCT) of patients. In one patient, aneurysm diameter increased (XSCT and 3DCT) more than 5 mm. Four patients who had a new onset endoleak had a much higher expansion rate than those with a chronic endoleak (P <.05). Conclusions: The rate of decrease in aneurysm size (annualized 3.4-4.1 mm/y) after endovascular repair of AAA approximates the reported expansion rate in untreated aneurysms. However, individual aneurysm behavior is unpredictable, and the presence of an endoleak is unreliable in predicting changes in diameter. New onset endoleaks are associated with an enlargement rate greater than that of untreated aneurysms. (J Vasc Surg 2000;32:108-15.

Iliac fixation inhibits migration of both suprarenal and infrarenal aortic endografts

ObjectiveTo evaluate the role of iliac fixation in preventing migration of suprarenal and infrarenal aortic endografts.MethodsQuantitative image analysis was performed in 92 patients with infrarenal aortic aneurysms (76 men and 16 women) treated with suprarenal (n = 36) or infrarenal (n = 56) aortic endografts from 2000 to 2004. The longitudinal centerline distance from the superior mesenteric artery to the top of the stent graft was measured on preoperative, postimplantation, and 1-year three-dimensional computed tomographic scans, with movement more than 5 mm considered to be significant. Aortic diameters were measured perpendicular to the centerline axis. Proximal and distal fixation lengths were defined as the lengths of stent-graft apposition to the aortic neck and the common iliac arteries, respectively.ResultsThere were no significant differences in age, comorbidities, or preoperative aneurysm size (suprarenal, 6.0 cm; infrarenal, 5.7 cm) between the suprarenal and infrarenal groups. However, the suprarenal group had less favorable aortic necks with a shorter length (13 vs 25 mm; P < .0001), a larger diameter (27 vs 24 mm; P < .0001), and greater angulation (19° vs 11°; P = .007) compared with the infrarenal group. The proximal aortic fixation length was greater in the suprarenal than in the infrarenal group (22 vs 16 mm; P < .0001), with the top of the device closer to the superior mesenteric artery (8 vs 21 mm; P < .0001) as a result of the 15-mm uncovered suprarenal stent. There was no difference in iliac fixation length between the suprarenal and infrarenal groups (26 vs 25 mm; P = .8). Longitudinal centerline stent graft movement at 1 year was similar in the suprarenal and infrarenal groups (4.3 ± 4.4 mm vs 4.8 ± 4.3 mm; P = .6). Patients with longitudinal centerline movement of more than 5 mm at 1 year or clinical evidence of migration at any time during the follow-up period comprised the respective migrator groups. Suprarenal migrators had a shorter iliac fixation length (17 vs 29 mm; P = .006) and a similar aortic fixation length (23 vs 22 mm; P > .999) compared with suprarenal nonmigrators. Infrarenal migrators had a shorter iliac fixation length (18 vs 30 mm; P < .0001) and a similar aortic fixation length (14 vs 17 mm; P = .1) compared with infrarenal nonmigrators. Nonmigrators had closer device proximity to the hypogastric arteries in both the suprarenal (7 vs 17 mm; P = .009) and infrarenal (8 vs 24 mm; P < .0001) groups. No migration occurred in either group in patients with good iliac fixation. Multivariate logistic regression analysis revealed that iliac fixation, as evidenced by iliac fixation length (P = .004) and the device to hypogastric artery distance (P = .002), was a significant independent predictor of migration, whereas suprarenal or infrarenal treatment was not a significant predictor of migration. During a clinical follow-up period of 45 ± 22 months (range, 12-70 months), there have been no aneurysm ruptures, abdominal aortic aneurysm–related deaths, or surgical conversions in either group.ConclusionsDistal iliac fixation is important in preventing migration of both suprarenal and infrarenal aortic endografts that have longitudinal columnar support. Secure iliac fixation minimizes the risk of migration despite suboptimal proximal aortic neck anatomy. Extension of both iliac limbs to cover the entire common iliac artery to the iliac bifurcation seems to prevent endograft migration

Explant analysis of AneuRx stent grafts: relationship between structural findings and clinical outcome

AbstractObjectiveWe reviewed the structural findings of explanted AneuRx stent grafts used to treat abdominal aortic aneurysms, and relate the findings to clinical outcome measures.MethodsWe reviewed data for all bifurcated AneuRx stent grafts explanted at surgery or autopsy and returned to the manufacturer from the US clinical trial and worldwide experience of more than 33,000 implants from 1996 to 2003. Devices implanted for more than 1 month with structural analysis are included in this article. Explant results were analyzed in relation to cause of explantation and pre-explant evidence of endoleak, enlargement, or device migration.ResultsOne hundred twenty explanted stent grafts, including 37 from the US clinical trial, were analyzed. Mean implant duration was 22 ± 13 months (range, 1-61 months). Structural abnormalities included stent fatigue fractures, fabric abrasion holes, and suture breaks. The mean number of nitinol stent strut fractures per explanted device was 3 ± 4, which represents less than 0.2% of the total number of stent struts in each device. The mean number of fabric holes per explanted device was 2 ± 3, with a median hole size of 0.5 mm2. Suture breaks were seen in most explanted devices, but composed less than 1.5% of the total number of sutures per device. “For cause” explants (n = 104) had a 10-month longer implant duration (P = .007) compared with “incidental” explants (n = 16). “For cause” explants had more fractures (3 ± 5; P = .005) and fabric holes (2 ± 3; P = .008) per device compared with “incidental” explants, but these differences were not significant (P = .3) when adjusted for duration of device implantation. Among clinical trial explants the number of fabric holes in grafts in patients with endoleak (2 ± 3 per device) was no different from those without endoleak (3 ± 4 per device; P = NS). The number of fatigue fractures or fabric holes was no different in grafts in clinical trial patients with pre-explant aneurysm enlargement compared with those without enlargement. Pre-explant stent-graft migration was associated with a greater number of stent strut fractures (5 ± 7 per device; P = .04) and fabric holes (3 ± 3 per bifurcation; P = .03) compared with explants without migration. Serial imaging studies revealed inadequate proximal, distal, or junctional device fixation as the probable cause of rupture or need for conversion to open surgery in 86% of “for cause” explants. Structural device abnormalities were usually remote from fixation sites, and no causal relationship between device findings and clinical outcome could be established.ConclusionsNitinol stent fatigue fractures, fabric holes, and suture breaks found in explanted AneuRx stent grafts do not appear to be related to clinical outcome measures. Longer term studies are needed to confirm these observations

Computational medicine, present and the future: obstetrics and gynecology perspective.

Medicine is, in its essence, decision making under uncertainty; the decisions are made about tests to be performed and treatments to be administered. Traditionally, the uncertainty in decision making was handled using expertise collected by individual providers and, more recently, systematic appraisal of research in the form of evidence-based medicine. The traditional approach has been used successfully in medicine for a very long time. However, it has substantial limitations because of the complexity of the system of the human body and healthcare. The complex systems are a network of highly coupled components intensely interacting with each other. These interactions give those systems redundancy and thus robustness to failure and, at the same time, equifinality, that is, many different causative pathways leading to the same outcome. The equifinality of the complex systems of the human body and healthcare system demand the individualization of medical care, medicine, and medical decision making. Computational models excel in modeling complex systems and, consequently, enabling individualization of medical decision making and medicine. Computational models are theory- or knowledge-based models, data-driven models, or models that combine both approaches. Data are essential, although to a different degree, for computational models to successfully represent complex systems. The individualized decision making, made possible by the computational modeling of complex systems, has the potential to revolutionize the entire spectrum of medicine from individual patient care to policymaking. This approach allows applying tests and treatments to individuals who receive a net benefit from them, for whom benefits outweigh the risk, rather than treating all individuals in a population because, on average, the population benefits. Thus, the computational modeling-enabled individualization of medical decision making has the potential to both improve health outcomes and decrease the costs of healthcare

Role of fibrinopeptide B in early atherosclerotic lesion formation

The development of atheroselerotic lesions involves many cell types, including macrophages. Fibrinopeptide B (FPB) has been shown to be a potent chemotactic agent for macrophages, which are abundant as intimal foam cells in atherosclerotic lesions, especially in cholesterol-fed rabbits. We hypothesize that intimal low-density lipoproteins also cause fibrinogen in the intima to release FPB and that FPB attracts macrophages in response to the high lipid levels associated with lesion development. To test our hypothesis, we used an atherosclerotic model. Silk sutures containing either FPB, fibrinopeptide A (FPA), lipopolysaccharide (LPS), or saline control were prepared. One suture of each type was placed in the adventitia of the femoral artery of a rabbit. Animals were killed at 1 or 2 weeks. Only vessels exposed to either FPB or LPS showed significant intimal thickening in the region adjacent to the suture site. Semi-thin electron microscopic sections indicated that the intimal wall was highly cellular and that many cells contained lipid vacuoles after 2 weeks. These sections also showed that the endothelium remained intact and that no injury to the media of the artery had occurred. Electron microscopy of the tissue samples showed the proliferation of smooth muscle cells and deposition of extracellular matrix in the 2-week animals, whereas foam cells were present in the l-week animals. We conclude that FPB does indeed attract macrophages to the intima and that these macrophages may become foam cells. The model we have developed can be used to study possible mechanisms for the entry of macrophages into the intima during early lesion development and to further understand the complex interactions of FPB, fibrinogen, and lipids in atherosclerotic lesion development. T he development ofatherosclerotic lesions is a complex process and probably involves interactions between circulating blood elements, including serum lipids and white blood cells (e.g., monocytes and lymphocytes), and the arterial wall, including endothelial cells and smooth muscle cells of the media. The nature of this interaction and the role of blood-borne cells in this process, especially macrophages, are not completely understood. From the Departments of Surgery and Fibrinogen is a serum protein with a major role in blood clotting. It may also be the source of a chemotactic factor for the monocytes that accumulate as intimal foam cells during atherogenesis. Three considerations point to such a mechanism. First, diet-induced hyperlipemia is associated with an increased influx of ape-B-containing lipoproteins into the intima The complex process involving the interactions of fibfinogen, FPB, and lipoproteins is not fully understood. One possible mechanism is that when fibrinogen binds to lipoproteins with the requisite phospholipid surface, the lipids become oxidized so that they cannot exit the vessel wall. Since there is also a release of FPB, we hypothesize that FPB attracts macrophages to deal with the offending agent (the altered lipids). Previous studies by Prescott et al MATERIAL AND METHODS Sixteen New Zealand White rabbits (3.0 to 3.5 kg) were used. 4.0 silk sutures were prepared by soaking them 15