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Background: Intimal hyperplasia (IH) is the most common indicator for secondary intervention in peripheral vascular disease. Matrix metalloproteinases (MMPs) play a role in IH development due to their degradation of the extracellular matrix. Doxycycline (Doxy), a member of the tetracycline family of antibiotics, is a potent MMP inhibitor. We have previously shown that Doxy inhibits MMP activity and vascular smooth muscle cell migration in vitro. We hypothesized that Doxy would decrease MMP activity in vivo and inhibit the development of IH in a rodent model of vascular injury., Methods and Results: Doxy (400 mg/pellet) was delivered by a slow-release pellet implanted 3 days prior to or at the time of balloon angioplasty (BA) of the common carotid artery in female rats. At 14 days post-BA, intima-to-media (I:M) ratios were 0.77 ± 0.21 and 1.04 ± 0.32 in the Doxy treated groups, respectively, compared to 1.25 ± 0.26 in the control group (P = not significant; n = 3). Additionally, the tested dose of Doxy in either group had no inhibitory effect on membrane type 1-MMP or MMP-2 tissue levels, as measured by immunohistochemistry, or on systemic levels of MMP, as measured by total MMP serum levels using enzyme-linked immunosorbent assay. At 14 days post-BA, VSMC proliferation in the injured artery was increased to Doxy treatment prior to and at the time of surgery (23.5 ± 3.4 and 27.2 ± 3.9%, respectively), compared to control (11.4 ± 0.4%; n = 3), as measured by proliferating cellular nuclear antigen immunostaining., Conclusions: In our in vivo model of vascular injury, systemic Doxy administration prior to or at the time of vascular injury does not significantly hinder the progression of IH development. Additional doses and routes of administration could be examined in order to correlate therapeutic serum levels of Doxy with effective MMP inhibition in serum and arterial tissue. However, alternative drug delivery systems are needed in order to optimize therapeutic administration of targeted MMP inhibitors for the prevention of IH development., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Postmenopausal women taking hormone replacement therapy (HRT) require secondary intervention after vascular reconstruction more frequently than women not taking HRT, often due to increased development of intimal hyperplasia (IH). Matrix metalloproteinases (MMPs) play a role in IH by degradation and remodeling of components of the vascular basement membrane. The MMP pathway is regulated by a balance between MMPs, membrane-type MMPs (MT-MMPs), and tissue inhibitor of MMPs (TIMPs). We have recently provided evidence for unbalanced regulation of the MT1-MMP/MMP-2 pathway in vascular smooth muscle cells (VSMCs) exposed to hormones in vitro. Herein we study the role of HRT in the development of IH in a postmenopausal rodent model of vascular injury and in the modulation of this MMP regulatory pathway in vivo., Methods: Female rats were aged to 12 months. Animals were ovariectomized (OVX) and 4 weeks later hormones or placebo was delivered via a 90-day slow-release pellet. After 6 weeks of HRT each rat underwent balloon angioplasty of the left common carotid artery. At 14 days postinjury tissue samples were collected and stained with trichrome elastin and for isoform-specific MMPs., Results: After vascular injury, the intima:media (I:M) ratio was decreased in OVX rats receiving placebos as compared with non-OVX controls (P < 0.05). In OVX animals receiving HRT, estrogen with and without progesterone and progesterone alone slightly increased I:M ratio compared with placebo, although no significant difference was found in any HRT group. Injury-induced intimal expression of MMP-2 and -9 was decreased in OVX placebo animals compared with non-OVX controls (P < 0.05). MMP-2 and -9 levels were subsequently increased by each type of hormone therapy compared with placebo, with a significant increase in MMP-9 in response to estrogen with and without progesterone (P < 0.05). Conversely, TIMP-2 was decreased by estrogen compared with placebo (P < 0.05). There was no effect on intimal MT1-MMP in any group., Conclusions: In this study we detected a statistically significant decrease in IH as a result of OVX. Subsequent HRT exposure resulted in increased I:M ratios compared with OVX animals given placebo, although significance was not reached with the doses given. Long-term exogenous exposure may have a more deleterious effect compared with acute exposure and should be examined further. We also demonstrated a significant reduction in MMP-2 and -9 and TIMP-2 in response to OVX. Subsequent hormone exposure resulted in the upregulation of MMP-2 and -9 without a counterregulatory increase in TIMP, indicating that HRT modulates the MMP regulatory pathway in vivo. The data suggest that the lack of hormones after OVX protects against pathologic remodeling in our aged model of disease and that exposure to both natural and exogenous hormones could be a negative risk factor resulting in an exaggerated vascular response to injury. Future studies should focus on in vivo manipulation of unbalanced MMP regulation for prevention of IH in response to HRT and in general. Furthermore, the age-associated difference in response to the presence of natural hormones in young vs aged models should be investigated., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Leg swelling is a common cause for vascular surgical evaluation, and iliocaval obstruction due to May-Thurner syndrome (MTS) can be difficult to diagnose. Physical examination and planar radiographic imaging give anatomic information but may miss the fundamental pathophysiology of MTS. Similarly, duplex ultrasonographic examination of the legs gives little information about central impedance of venous return above the inguinal ligament. We have modified the technique of duplex ultrasonography to evaluate the flow characteristics of the leg after tourniquet-induced venous engorgement, with the objective of revealing iliocaval obstruction characteristic of MTS. Twelve patients with signs and symptoms of MTS were compared with healthy control subjects for duplex-derived maximal venous outflow velocity (MVOV) after tourniquet-induced venous engorgement of the leg. The data for healthy control subjects were obtained from a previous study of asymptomatic volunteers using the same MVOV maneuvers. The tourniquet-induced venous engorgement mimics that caused during vigorous exercise. A right-to-left ratio of MVOV was generated for patient comparisons. Patients with clinical evidence of MTS had a mean right-to-left MVOV ratio of 2.0, asymptomatic control subjects had a mean ratio of 1.3, and MTS patients who had undergone endovascular treatment had a poststent mean ratio of 1.2 (P = 0.011). Interestingly, computed tomography and magnetic resonance imaging results, when available, were interpreted as positive in only 53% of the patients with MTS according to both our MVOV criteria and confirmatory venography. After intervention, the right-to-left MVOV ratio in the MTS patients was found to be reduced similar to asymptomatic control subjects, indicating a relief of central venous obstruction by stenting the compressive MTS anatomy. Duplex-derived MVOV measurements are helpful for detection of iliocaval venous obstruction, such as MTS. Right-to-left MVOV ratios and postengorgement spectral analysis are helpful adjuncts to duplex imaging for leg swelling. The MVOV maneuvers are well tolerated by patients and yields physiological data regarding central venous obstruction that computed tomography and magnetic resonance imaging fail to detect., (Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

The purposes of this study were to develop and validate the (1) Rapid Estimate of Adult Literacy in Vascular Surgery (REAL&#95;VS) for researchers studying the impact of literacy skills as related to vascular surgery-related knowledge and outcomes and (2) short version of the REAL&#95;VS (REAL&#95;VSs) to allow clinicians to gauge their patients' familiarity with vascular surgery-related terms. A three-phase process was used to identify potential words for inclusion in the REAL&#95;VS, including reviewing Internet-based patient education material content and listening to a random sample of 50 archived audiorecordings of vascular surgeon-patient encounters. The REAL&#95;VS was composed of 75 terms (e.g., stent, gangrene, invasive, aneurysm) of varying pronunciation difficulty. One hundred fifty-two English-speaking patients (>or=18 years of age) attending a university-based vascular surgery clinic were recruited to participate in this study (mean age = 61.4 +/- 14.6 years). During face-to-face interviews, patients' sociodemographic information was collected, and patients were administered the widely used Rapid Estimate of Adult Literacy in Medicine (REALM) and REAL&#95;VS. Mean scores on the REALM (56.9 +/- 14.0) and REAL&#95;VS (63.3 +/- 15.6) were highly correlated (Spearmans rank correlation [rho] = 0.91; p < 0.00). Internal consistency of the REAL&#95;VS (Cronbachs alpha = 0.98) was excellent. Mean scores on the REAL&#95;VSs (4.1 +/- 2.7) were highly correlated with both the REALM (rho = 0.82; p < 0.00) and REAL&#95;VS (rho = 0.94; p < 0.00). Internal consistency, measured using Cronbachs alpha, of the REAL&#95;VSs was 0.86. This study demonstrates that both the REAL&#95;VS and REAL&#95;VSs are both promising tools for use in vascular surgery research and clinical practice, respectively.

Venous thoracic outlet syndrome (V-TOS) and associated subclavian vein thrombosis (SVT) result in significant patient morbidity and can be difficult to manage. Previous studies have suggested that both mechanical compressive factors and pathological alterations in patient coagulation may contribute to the development of SVT; however, no study has specifically evaluated the role of thrombophilia in the treatment of V-TOS and the need for long-term anticoagulation as an adjunct to surgical decompression. This retrospective study describes the clinical courses of 18 patients treated for V-TOS with and without acute SVT. In this review, 67% of patients with SVT are found to have relatively common coagulation disorders and 90% of postoperative complications were associated with some form of thrombophilia. This study suggests that thrombophilia may play an important role in the pathogenesis of V-TOS and may be a determinant of the success of surgical decompression. Clotting disorders should therefore be aggressively evaluated in this patient population and can improve therapeutic outcome.

Leukocyte and platelet adhesion to endothelial cells, an early step in the pathogenesis of atherosclerosis, is mediated through adhesion molecules. It has been shown that statins decrease adhesion molecule expression. We examined the hypothesis that fluvastatin decreased intercellular adhesion molecule-1 (ICAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) expression through a nitric oxide-mediated pathway. Human iliac artery endothelial cells were exposed to fluvastatin in the presence or absence of 2 mM N-monomethyl-L-arginine (L-NMMA). Flow cytometry analysis was used to measure ICAM-1 and PECAM-1 expression. In a separate experiment, confluent cell cultures were exposed in a serum-free medium to fluvastatin 20 microM, and the supernatant was collected for nitrate/nitrite determination after 6 and 48 hr of incubation. Protein was isolated and processed for immunoblotting with monoclonal antibodies specific for endothelial nitric oxide synthase (eNOS), Ser(1177)-phosphorylated eNOS, and AMP kinase. Relative band intensity was assessed with densitometry. Results are presented as the mean +/- standard deviation (SD), and p < 0.05 was considered significant. ICAM-1 and PECAM-1 were expressed constitutively. Human iliac artery endothelial cells (HIAECS) treated with 5 microM fluvastatin did not exhibit reduced expression of PECAM-1 or ICAM-1. Incubation with 10 microM fluvastatin reduced basal expression of both ICAM-1 and PECAM-1. Fluorescence intensity (FI) for these substance was as follows: 3638 +/- 1671, p = 0.01 and PECAM-1 vs. control FI 276 +/- 52 vs. 522 +/- 78, p = 0.02. In the presence of 2 mM L-NMMA, fluvastatin failed to decrease the expression of ICAM-1 (fluvastatin 10 microM + L-NMMA: FI was 3042 +/- 1378 vs. 3638 +/- 1671 for the control p = 0.01) or PECAM-1 (fluvastatin 10 microM + L-NMMA: FI was 415 +/- 188 vs. 522 +/- 78 for the control, p = 0.1). Incubation with 20 microM fluvastatin similarly reduced ICAM-1 expression (FI was 2014 +/- 1595 vs. 3638 +/- 1671 for the control, p = 0.02) and PECAM-1 expression (FI was 196 +/- 109 vs. 522 +/- 78 for the control, p = 0.02). This reduction was prevented in the presence of 2 mM L-NMMA. L-NMMA in a concentration of 2 mM had no significant effect on adhesion molecule expression (p > 0.05 for all comparisons of the control FI versus 2 mM L-NMMA mean FI). After a 48 hr incubation with 20 microM fluvastatin there was a 219 +/- 35% increase in the cell eNOS protein content (p = 0.01) and a 170 +/- 26% increase in the cell AMPK protein content (p = 0.02). Ser(1177)-phosphorylated eNOS protein levels were increased by 41 +/- 8% (p = 0.03). The nitric oxide concentration in the medium of the HIAEC treated with 20 microM fluvastatin for 48 hr was significantly higher than that in the control (p = 0.0004), pointing to increased production during the incubation period. Fluvastatin thus decreases basal expression of ICAM-1 and PECAM-1. Competitive inhibition of eNOS with L-NMMA abolishes the effect of fluvastatin on ICAM-1 and PECAM-1 expression. The statin up-regulates eNOS and AMP kinase, one of the enzymes that activates eNOS via phosphorylation at Ser(1177). We have shown that after a 48-hr exposure to fluvastatin there is an increased amount of the phosphorylated enzyme in the endothelial cells.

Open abdominal aortic aneurysm repair has been reported to be associated with impairment of sexual function in men, most likely because of autonomic nerve injury and pelvic blood flow changes. Endovascular aneurysm repair does not involve dissection in the area of the iliac bifurcation and therefore may be associated with lower incidence of sexual dysfunction as compared to open repair. We conducted a retrospective study of males after open and endovascular abdominal aortic aneurysm repair to determine if there is a significant difference in the incidence of sexual dysfunction between the two procedures. A modified International Index of Erectile Function Questionnaire was used to access sexual function before and after aneurysm repair. The questionnaire was mailed to all male patients who underwent abdominal aortic aneurysm repair from January 1, 1999 to July 15, 2002. The questionnaire asked patients questions regarding their sexual function before and 3 months after the repair. Questionnaire scores for domains of sexual function (erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction) as well as the total questionnaire score were analyzed. The chi-square and Wilcoxon's signed ranks test were used for statistical comparisons, with p < 0.05 considered significant. Logistic regression was used to examine association. Two hundred ninety-three questionnaires were mailed and 90 were returned completed. There was no difference for the total questionnaire score or the erectile function score before the procedure. Based on the questionnaire score, erectile function worsened after open AAA repair ( p = 0.002). Orgasmic function also deteriorated after open AAA repair ( p = 0.001). Endovascular repair was not accompanied by decreased erectile or orgasmic function ( p = 0.057 and p = 0.068, respectively). Impairment of erectile function was not associated with age, diabetes, or the number of patent hypogastric arteries after aneurysm repair, but there was a significant association between impaired erectile function and open aneurysm repair ( p = 0.036). Endovascular repair of abdominal aortic aneurysms is associated with significantly less impairment of erectile and orgasmic function than that with open repair. Preservation of sexual function after endovascular as compared to open repair should be among the factors considered when weighing treatment options for an abdominal aortic aneurysm in a sexually active male.

Symptomatic peripheral septic embolism is a rare systemic complication of infective endocarditis. This case report describes abdominal pain secondary to a septic pseudoaneurysm in the distal superior mesenteric artery. Presentation, imaging, surgical intervention, and histologic evaluation are described, and a review of recent literature relating to this phenomenon is outlined.

Previous investigations reveal in the absence of endothelial cell (EC) injury, intraarterial polytetrafluoroethylene (PTFE) stent graft (SG) exhibit greater EC repaving than PTFE interposition grafts (CG). The investigation evaluated EC repaving of SG compared to CG after balloon injury. Twenty adult dogs underwent SG (n = 10) or CG (n = 10) placement in the infrarenal aorta after balloon injury with harvest at 1 and 6 weeks. Endothelial repaving, intima-to-media height ratios (IMHR), and inflammatory stains were performed. Endothelial repaving was greater in 6-week SG compared to CG (51% +/- 5.0 versus 10% +/- 5.0, p < or = 0.05). IMHR was less in 6-week SG compared to CG at the proximal (1.22 +/- 0.16 versus 1.82 +/- 0.16, p < or = 0.05) and distal anastomosis (0.81 +/- 0.25 versus 1.33 +/- 0.25, p < or = 0.05). Smooth muscle cell (SMC) alpha-actin was greater in 1-week SG compared to CG at the distal anastomosis (121.5 +/- 7.2 versus 94.0 +/- 7.2, p < or = 0.05). Proliferating cell nuclear antigen (PCNA) was less in 6-week SG compared to CG at the proximal (5.6 +/- 1.4 versus 9.4 +/- 1.1, p < or = 0.05) and distal anastomosis (3.8 +/- 0.6 versus 11.2 +/- 1.1, p < or = 0.05). Macrophage CD-44 was less in 6-week SG compared to CG at the proximal (10.4 +/- 1.6 versus 32.6 +/- 3.6, p < or = 0.05) and distal anastomosis (8.6 +/- 0.9 versus 35.6 +/- 3.6, p < or = 0.05). Intraarterial SG placed after balloon injury exhibited significantly greater endothelialization and less intimal hyperplasia when compared to CG.

Symptoms of chronic subclavian occlusion including swelling and pain may be disabling. In the case presented a patient with disabling symptoms 18 years after ligation of the right subclavian vein during resection of a chest wall tumor is successfully treated with a single-anastomosis internal jugular venous bypass.