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Although excellent operative results can be achieved in cases of non-ischemic complications, acute femoral occlusion in children younger than 2 years often leads to less satisfactory outcomes. Operative intervention can provide successful outcome in children with claudication caused by chronic limb ischemia. Variables that correlated with significant iatrogenic groin complications included a young age, therapeutic intervention, earlier catheterization, and the use of a large guiding catheter.

SUMMARYWe present an overview of how the arterial fluid mechanics problems can be modeled with the stabilized space-time fluid-structure interaction (SSTFSI) technique developed by the Team for Advanced Flow Simulation and Modeling (T AFSM). The SSTFSI technique includes the enhancements introduced recently by the T AFSM to increase the scope, accuracy, robustness and efficiency of this class of techniques. The SSTFSI technique is supplemented with a number of special techniques developed for arterial fluid mechanics modeling. These include a recipe for pre-FSI computations that improve the convergence of the FSI computations, using an estimated zero-pressure arterial geometry, and the sequentially coupled arterial FSI (SCAFSI) technique. The recipe for pre-FSI computations is based on the assumption that the arterial deformation during a cardiac cycle is driven mostly by the blood pressure. The SCAFSI technique, which was introduced as an approximate FSI approach in arterial fluid mechanics, is also based on that assumption. The need for an estimated zero-pressure arterial geometry is based on recognizing that the patient-specific image-based geometries correspond to time-averaged blood pressure values. In our arterial fluid mechanics modeling the arterial walls can be represented with the membrane or continuum elements, both of which are geometrically nonlinear, and the continuum element is made of hyperelastic (Fung) material. Test computations are presented for cerebral and abdominal aortic aneurysms, where the arterial geometries used in the computations are close approximations to the patient-specific image-based data.

SUMMARYThe stabilized space-time fluid-structure interaction (SSTFSI) techniques developed by the Team for Advanced Flow Simulation and Modeling (T AFSM) are applied to FSI modelling in arterial fluid mechanics. Modelling of flow in arteries with aneurysm is emphasized. The SSTFSI techniques used are based on the deforming-spatial-domain/stabilized space-time (DSD/SST) formulation and include the enhancements introduced recently by the T AFSM to increase the scope, accuracy, robustness and efficiency of these techniques. The arterial structures can be modelled with the membrane or continuum elements, both of which are geometrically nonlinear, and the continuum element can be made of linearly elastic or hyperelastic material. Test computations are presented for cerebral and abdominal aortic aneurysms and carotid-artery bifurcation, where the arterial geometries used in the computations are close approximations to the patient-specific image-based data.

Objective-Although HIV protease inhibitors have been successfully used against HIV infection, many metabolic side effects and premature cardiovascular diseases are often associated with this therapy. The mechanisms of these complications are not clear. In this study, we investigated the effect of the HIV protease inhibitor ritonavir on human endothelial cell cultures. Methods and Results-By using nonradioactive cell proliferation and cytotoxicity assays, human endothelial cells treated with ritonavir showed a significant decrease in cell viability and an increase in cytotoxicity in a time-and dose-dependent fashion. Mitochondrial DNA was also substantially damaged with ritonavir treatment by long polymerase chain reaction analysis. In contrast, ritonavir had a very limited effect on endothelial apoptosis, as assessed by analyses of DNA fragmentation and cellular caspase-3 activity. Conclusions-These data demonstrate, for the first time, that the HIV protease inhibitor ritonavir at concentrations near clinical plasma levels is able to directly cause endothelial mitochondrial DNA damage and cell death mainly through necrosis pathways but not through apoptosis. This study suggests that HIV protease inhibitor-mediated endothelial injury may contribute to its cardiovascular complications. Key Words: HIV protease inhibitor Ⅲ ritonavir Ⅲ cytotoxicity Ⅲ endothelial cells Ⅲ cardiovascular disease H uman immunodeficiency virus protease is an important virally encoded enzyme that cleaves the gag and gagpol protein precursors to produce mature and infectious virus particles. Thus, HIV protease has been the target of antiviral therapy. HIV protease inhibitors were introduced in 1995 for the treatment of HIV-infected patients. HIV protease inhibitors, including saquinavir, ritonavir, indinavir, nelfinavir, and amprenavir, rapidly and profoundly reduce the viral load, as indicated by a decline in plasma HIV RNA concentrations within a few days after the start of treatment. 1,2 Reductions in the viral load are paralleled by mean increases in the CD4ϩ count of 100 to 150 cells/mm 3 . 3,4 However, HIV protease inhibitors are often associated with a number of metabolic side effects and cardiovascular complications. The major concern raised by protease inhibitor-associated elevation in plasma levels of cholesterol and triglycerides relates to the risk of premature development of atherosclerosis. 5-7 Indeed, rapidly evolving plaques may be particularly unstable and thus prone to rupture, generating an acute coronary event in HIV protease inhibitor-treated patients. 8 However, the mechanisms of HIV protease inhibitor-associated cardiovascular disease are not known.Normal endothelial cell function and integrity are crucial in preventing vascular disease formation and thrombosis. We hypothesized that HIV protease inhibitors could cause endothelial injury or dysfunction by either direct cytotoxic effect or indirect effect of protease inhibitor-related metabolic changes on endothelial cell growth and function. In the present study, we in...

Cigarette smoking is an important risk factor for both vascular disease and various forms of cancer. Vascular endothelial growth factor (VEGF) is an endothelial-specific mitogen that is normally expressed only in low levels in normal arteries but may be involved in the progression of both vascular disease and cancer. Some clinical evidence suggests that cigarette smoking may increase plasma VEGF levels, but there is a lack of basic science studies investigating this possibility. We show here, using an intact porcine common carotid artery perfusion culture model, that nicotine and cotinine, the major product of nicotine metabolism, cause a significant increase in endothelial cell VEGF expression. VEGF mRNA levels were compared between groups using reverse transcriptase-polymerase chain reaction, whereas protein level changes were demonstrated with Western blotting and immunohistochemistry. Our results showed significant increases in endothelial cell VEGF mRNA and protein levels because of nicotine and cotinine at concentrations representative of plasma concentrations seen in habitual smokers. VEGF immunostaining also paralleled these results. These findings may give a clue as to the mechanisms by which nicotine and cotinine from cigarette smoking increase vascular disease progression and tumor growth and metastasis.

Erectile dysfunction after HAE correlates with significant reduction in PBI. Severe pelvic ischemic symptoms are more likely to occur after bilateral HAE, which should be avoided if possible. Moreover, patients with diseased PFA are at risk of development of pelvic ischemia after HAE. Our data suggest a potential role of concomitant profundapalsty at the time of aortic endografting to improve pelvic collateral flow and reduce pelvic ischemia in this subset of patients with HAE.

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