Murray L. Shames

Treatment with simvastatin suppresses the development of experimental abdominal aortic aneurysms in normal and hypercholesterolemic mice.

Objective:To determine if treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) can influence the development of experimental abdominal aortic aneurysms (AAAs). Summary Background Data:AAAs are associated with atherosclerosis, chronic inflammation, and matrix metalloproteinase (MMP)-mediated connective tissue destruction. Because statins exert antiinflammatory activities independent of their lipid-lowering effects, these agents may help suppress aneurysmal degeneration. Methods:C57Bl/6 wild-type and hypercholesterolemic apoE-deficient mice underwent transient perfusion of the aorta with elastase followed by subcutaneous treatment with either 2 mg/kg simvastatin per day or vehicle. Aortic diameter (AD) was measured before and 14 days after elastase perfusion. The extent of aortic dilatation (ΔAD) was determined with AAAs defined as ΔAD >100%. Results:Wild-type mice treated with simvastatin exhibited a 21% reduction in ΔAD and a 33% reduction in AAAs compared with vehicle-treated controls. Suppression of AAAs in simvastatin-treated mice was associated with preservation of medial elastin and vascular smooth muscle cells, as well as a relative reduction in aortic wall expression of MMP-9 and a relative increase in expression of TIMP-1. In hypercholesterolemic apoE-deficient mice, treatment with simvastatin was associated with a 26% reduction in ΔAD and a 30% reduction in AAAs. Treatment with simvastatin had no effect on serum cholesterol levels in either normal or hypercholesterolemic mice. Conclusions:Treatment with simvastatin suppresses the development of experimental AAAs in both normal and hypercholesterolemic mice. The mechanisms of this effect are independent of lipid-lowering and include preservation of medial elastin and smooth muscle cells, as well as altered aortic wall expression of MMPs and their inhibitors.

An Overview of Matrix Metalloproteinases in the Pathogenesis and Treatment of Abdominal Aortic Aneurysms

Recent basic and clinical research has established a link between the pathogenesis of abdominal aortic aneurysms (AAA) and matrix metalloproteinases (MMP). The discovery of the influence of MMPs on in vitro and in vivo aneurysm development has yielded promising information that may eventually decode the pathogenetic factors affecting the initiation and growth rate of AAAs. In this review, an analysis of MMPs involved in AAA disease is presented, including the data from recent research studies and planned clinical drug trails designed to retard the AAA growth by inhibiting MMP activity.

Current Indications for Preoperative Inferior Vena Cava Filter Insertion in Patients Undergoing Surgery for Morbid Obesity

Background: Pulmonary embolus is a potentially lethal complication in patients undergoing surgery for morbid obesity. In a select group of patients at high risk for venous thromboembolic events (VTE), we have chosen to prophylactically insert inferior vena cava filters via a jugular percutaneous approach. We propose guidelines for preoperative insertion of inferior vena cava filters in patients with clinically significant obesity. Methods: All patients who underwent preoperative insertion of inferior vena cava (IVC) filters as prophylaxis for pulmonary emboli were reviewed. Data regarding body mass index (BMI), prior history of venous thromboembolism, current anticoagulant usage, as well as other patient data were compiled and analyzed. Additionally, all operative notes were reviewed, and operative data were analyzed and compared. Results: 14 patients underwent preoperative IVC filter placement before gastric bypass. Mean patient age was 49.1 ± 1.52 years and mean BMI was 56.5 ± 4.45 kg/m2. No complications occurred due to preoperative filter placement, and no pulmonary emboli occurred in this group. Indications for preoperative IVC filter insertion included prior pulmonary embolus (6), prior deep venous thrombosis (7), and lower extremity venous stasis (1). Conclusions: Vena caval filter placement in the preoperative period can be undertaken safely in bariatric patients. We recommend that routine preoperative vena caval filter placement should be undertaken in all bariatric patients with prior pulmonary embolus, prior deep venous thrombosis, evidence of venous stasis, or known hypercoagulable state. Possible roles for IVC filter placement in this patient population are expanding as more data is acquired.

Outcome of carotid stent-assisted angioplasty versus open surgical repair of recurrent carotid stenosis

PURPOSE We compared outcome and durability of carotid stent-assisted angioplasty (CAS) with open surgical repair (ie, repeat carotid endarterectomy [CEA]) to treat recurrent carotid stenosis (RCS). METHODS A retrospective review of anatomic and neurologic outcomes was carried out after 27 repeat CEA procedures (1993-2002) and 52 CAS procedures (1997-2002) performed to treat high-grade internal carotid artery (ICA) RCS after CEA. The incidence of intervention because of symptomatic RCS was similar (repeat CEA, 63%; CAS, 60%), but the interval from primary CEA to repeat intervention was greater (P <.05) in the repeat CEA group (83 +/- 15 months) compared with the CAS group (50 +/- 8 months). In the CAS group, 17 of 52 arteries (33%) were judged not to be surgical candidates because of surgically inaccessible high lesions (n = 8), medical comorbid conditions (n = 4), neck irradiation (n = 3), or previous surgery with cranial nerve deficit or stroke (n = 2). Three patients who underwent repeat CEA had lesions not appropriate for treatment with CAS. RESULTS Overall 30-day morbidity was similar after CAS (12%; death due to ipsilateral intracranial hemorrhage, 1; nondisabling stroke, 1; reversible neurologic deficits or transient ischemic attack, 2; access site complication, 2). and repeat CEA (11%; no death; nondisabling stroke, 1; reversible cranial nerve injury, 1; cervical hematoma, 1). Combined stroke and death rate was 3.7% for repeat CEA and 5.7% for CAS (P >.1). All duplex ultrasound scans obtained within 3 months after CEA and CAS demonstrated patent ICA and velocity spectra of less than 50% stenosis. During follow-up, no repeat CEA (mean, 39 months) or CAS (mean, 26 months) repair demonstrated ICA occlusion, but two patients (8%) who underwent repeat CEA and 4 patients (8%) who underwent CAS required balloon or stent angioplasty because of 80% RCS. At last follow-up, no patient had ipsilateral stroke and all ICA remain patent. At duplex scanning, stenosis-free (<50% diameter reduction) ICA patency at 36 months was 75% after repeat CEA and 57% after CAS (P =.26, log-rank test). CONCLUSIONS Carotid angioplasty for treatment of high-grade stenotic ICA after CEA resulted in similar anatomic and neurologic outcomes compared with open surgical repair. Most lesions are amenable to endovascular therapy, and CAS enabled treatment in patients judged not to be suitable surgical candidates. Duplex scanning surveillance after repeat CEA or CAS is recommended, because stenosis can recur after either secondary procedure.

Transient exposure to elastase induces mouse aortic wall smooth muscle cell production of MCP-1 and RANTES during development of experimental aortic aneurysm☆

PURPOSE Abdominal aortic aneurysm (AAA) is associated with chronic transmural inflammation and destruction of the elastic media. The purpose of this study was to elucidate molecular mechanisms that might orchestrate leukocyte recruitment into the outer aortic wall by determining whether CC chemokines contribute to development of aneurysm degeneration in an elastase-induced mouse model of AAA. METHODS Adult male C57BL/6J mice underwent transient elastase perfusion of the abdominal aorta to induce development of AAA. At various intervals after elastase perfusion (0, 4, 7, 14 days), real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays were used to measure aortic wall expression of the CC (beta) chemokines, monocyte chemoattractant protein-1 (MCP-1) and regulated on activation, normal T-cell expressed and secreted (RANTES). Expression of these chemokines by cultured mouse aortic smooth muscle cells (AoSMC) was similarly assessed after transient (5 minutes) exposure to elastase solutions in vitro. RESULTS Mouse aortic diameter (mean +/- SEM) increased to aneurysmal proportions by 14 days after elastase perfusion (from 0.51 +/- 0.03 mm to 1.34 +/- 0.32 mm; 163% increase; P <.05), with macrophage infiltration of the outer aortic wall beginning within 7 to 10 days. Increased aortic wall messenger RNA expression for MCP-1 (28-fold) and RANTES (11-fold) was observed on day 4, with maximal production of chemokine protein on day 7 (MCP-1, from 7.07 +/- 0.06 ng/mL to 19.60 +/- 0.19 ng/mL; P <.001; RANTES, from 0.23 +/- 0.006 ng/mL to 2.03 +/- 0.057 ng/mL; P <.001). Neither MCP-1 nor RANTES was detected in normal mouse aorta with immunohistochemistry, but both chemokines were abundant in AAA. Within 48 hours of transient exposure to elastase, cultured mouse AoSMC exhibited pronounced induction (>90-fold) of MCP-1 and RANTES, despite concomitant decrease in cell numbers. CONCLUSIONS Increased mouse aortic wall expression of MCP-1 and RANTES occurs early in development of elastase-induced AAA and before onset of the chronic inflammatory response. Moreover, elastase directly stimulates AoSMC chemokine production in vitro. Elastase-induced medial SMC production of CC chemokines may therefore provide an important link between enzymatic injury, leukocyte recruitment, and aneurysmal degeneration of the aortic wall.

Magnetic resonance angiography minimizes need for arteriography after inadequate carotid duplex ultrasound scanning

PURPOSE We prospectively evaluated whether magnetic resonance angiography (MRA) enabled definition of cerebrovascular anatomy after indeterminate or inadequate results at duplex ultrasound scanning to facilitate patient selection for carotid endarterectomy (CEA) and for technical planning. METHODS After implementation of a protocol in October 1998 to minimize use of cerebral arteriography, MRA (arch/cervical two-dimensional and cranial three-dimensional time of flight technique) was performed in 138 consecutive patients with cerebrovascular occlusive disease and inconclusive duplex scans obtained by an ICAVL-approved laboratory. The ability of MRA to define anatomic features unresolved at duplex scanning was compared between categories of duplex scan inadequacies. Operative outcome was compared between patients requiring MRA before CEA (n = 66) and a concurrent cohort undergoing CEA on the basis of duplex scan results only (n = 69). RESULTS Incomplete imaging of the carotid bifurcation, because of high bifurcation, long (>3 cm) internal carotid artery (ICA) plaque, or calcific shadows, was the most common reason for inadequate duplex scans (n = 74, 53%), followed by borderline severe ICA disease (23.17%), suspected extracervical disease (supra-aortic trunk, vertebral, or intracranial, 22, 16%), ICA near- occlusion (12.9%), and diffuse recurrent stenosis (7.5%). MRA enabled resolution of duplex scan inadequacies in 95% of patients with disease confined to the carotid bifurcation, and 90% of all patients, but was least accurate for delineation of extracervical lesions (77%) and near-occlusions (75%). In 5 of 8 patients (6%) arteriography was performed to determine operability of ICA near-occlusion or extracervical lesions. Combined stroke and death rates after CEA were not statistically different (P =.3) between patients requiring MRA (3 of 66, 4.6%) and the concurrent group in whom MRA was performed solely on the basis of duplex results (1 of 69, 1.5%). However, intraoperative technical adjustments (anatomy that precluded shunt use, extended endarterectomy length, ICA shortening due to tortuosity) were planned in 71% of patients (12 of 17) with MRA-defined anatomy, but only 36% of patients (4 of 11) with long CEA on the basis of duplex results only (P =.08). CONCLUSION MRA replaces the need for cerebral arteriography in most patients after inadequate carotid duplex scanning. Delineation of cerebrovascular anatomy at MRA assists in determination of CEA candidacy and operative planning.

Regional antibiotic delivery for the treatment of experimental prosthetic graft infections.

OBJECTIVES To evaluate the efficacy of antibiotic-impregnated polymethylmethacrylate (PMMA) beads in eradication of an arterial prosthetic graft methicillin-resistant Staphylococcus aureus (MRSA) biofilm in an experimental animal model. METHODS Forty rats underwent subcutaneous implantation of a MRSA-colonized arterial polytetrafluoroethylene (PTFE) 1 x 1 cm wafer on the back. The effect of regional antibiosis produced by antibiotic PMMA bead placement adjacent to the infected PTFE wafer was determined using four 10-animal study groups: control (no antibiotic), PMMA bead with no antibiotic, PMMA bead with 10% vancomycin, and PMMA bead with 10% daptomycin. After 3 d, the PTFE wafers were explanted and quantitative biofilm cultures, expressed as colony-forming units (CFU) per graft wafer, performed using real-time polymerase chain reaction to assess MRSA eradication. No systemic antibiotic was administered. Bioassays of antibiotic bead bacteriocidal were performed by measuring zone of inhibition diameters on MRSA colonized agar culture plates prior to and following graft explantation. RESULTS All animal tolerated implantation of the MRSA-infected PTFE wafer and survived the 3 d until graft explantation. Quantitative biofilm cultures demonstrated a significant decrease (P < 0.01) in MRSA CFUs present on the PTFE wafer surfaces in the presence of both the vancomycin- and daptomycin-impregnated beads compared to controls and plain PMMA beads. Both vancomycin and daptomycin PMMA beads retained antibacterial activity after 3 d of implantation with decrease in zones of inhibition of 15% and 45%, respectively. CONCLUSIONS Regional antibiotic delivery using an antibiotic-impregnated PMMA bead reduced the bacterial biofilm concentration in experimental subcutaneous pocket model of vascular surgical site infection. The delivery of antibiotics via a PMMA bead may be a useful adjunct in the treatment of vascular surgical site infection.

Superior Mesenteric Artery Stent Fracture Producing Stenosis and Recurrent Chronic Mesenteric Ischemia: Case Report

Endovascular modalities are being increasingly employed in the treatment of a variety of vascular diseases. With new technologies come novel complications, and one such complication unique to endovascular surgery is stent fracture. We present two cases of stent fracture following stenting of the superior mesenteric artery and discuss possible causes and treatments.

Evaluation of the porcine model to teach various ancillary procedures to gynecologic oncology fellows.

OBJECTIVE The purpose of this study was to subjectively evaluate the adequacy of the porcine model for training gynecologic oncology fellows. STUDY DESIGN Following a defined surgical curriculum, fellow-attending pairs operated on female hogs. A predetermined dataset was collected for each procedure. RESULTS Twenty pigs were operated on. The porcine model was determined to be a good model for laparoscopic lymphadenectomy (11), ureteroneocystostomy (7), repair of vascular injury (11), bowel anastamoses (21), distal pancreatectomy (5), nephrectomy (6), partial hepatectomy (5), diaphram stripping (5), and diaphragmatic resection (4). Two attendings and 1 fellow judged the porcine model to be fair (remaining 11 good) for ileocolonic urinary diversion, mainly due to significant differences in anatomy. Liver mobilization (5) and splenectomy (11) were determined to be fair or poor models by all participants due to the limited attachments in the pig. CONCLUSION The porcine model is adequate for teaching some ancillary gynecologic oncology surgical procedures and is inadequate for others.

Delayed Complications after Endovascular AAA Repair in Women

PURPOSE To assess whether women suffer more delayed complications or require more interventions after endovascular abdominal aortic aneurysm (AAA) repair. METHODS Over a 2-year period, 245 patients (203 men, 42 women) underwent endovascular repair with the AneuRx stent-graft at our institution. Baseline, operative, and follow-up data were reviewed and outcomes compared between men and women for complications or secondary procedures beyond the 30-day postoperative period. RESULTS The 42 (17.1%) women treated with the AneuRx graft experienced more technical complications (17% versus 8.3%; p<0.05) and acute conversions to open repair (6/7, 86%; p=0.0005). At 30 days, systemic morbidity was significantly higher in women (26% versus 5.3%; p=0.001.) However, mortality (2.3% versus 1.5%), length of hospital stay (2.6 versus 2.9 days), and major endoleaks at discharge (0% versus 1.6%) were similar. Over a mean follow-up of 11.3 months (range 1-26), graft limb occlusion occurred more frequently in female patients (12.2% versus 2.5%; p=0.05), and secondary procedures were required in a significantly higher number of women (29% versus 9%; p<0.05). Three patients in each group (25% of women versus 17% of men) who had secondary procedures required additional interventions. Although not statistically significant, the mortality in women during follow-up was higher (9.7% versus 5%); 2 deaths were directly related to graft complications in the female group. CONCLUSIONS Endoluminal AAA repair in women presents a technical challenge at the time of operation and may cause more frequent late complications, necessitating close postprocedural surveillance and prompt correction of complications to avoid potentially catastrophic outcomes. Reassessment of inclusion criteria for women may be necessary.