VASCULAR SURGERY A Fatty Acid Binding Protein, FABP4, Alters a Metabolic Enzyme that Plays a Major Role in Macrophage Inflammation, and Wound Healing Anna Eliassen, MD, Andrew Kimball, MD, Amrita Joshi, PhD, Steve Kunkel, PhD, Katherine Gallagher, MD University of Michigan, Ann Arbor, MI INTRODUCTION: Wound healing in chronic inflammatory diseases, such as diabetes, is impaired due to failed resolution of inflammation. We have previously found that SIRT3, a mitochondrial deacytlase enzyme, plays an important role in mediating macrophage inflammation in wound healing. Recent studies suggest that a fatty acid binding protein, FABP4, may regulate SIRT3 expression. We investigated the role of FABP4 in inflammation in wound macrophages. METHODS: C57BL/6 mice were fed either a normal diet or a high fat diet (HFD) for 12 weeks. They subsequently underwent 4-mm hindlimb wounds, and CD3-CD19-NK1.1-CD11b+ (macrophages) were isolated from mouse wounds on day 3 (previously found to be the day SIRT3 was significantly upregulated in wounds) using magnetic bead sorting. FABP4 expression was quantified by qPCR, and protein quantification performed using Western blot. RESULTS: CD3-CD19-NK1.1-CD11b+ (macrophages) isolated from murine wounds demonstrated a significant 30-fold increase in FABP4 gene expression on day 3 in the HFD mice compared with normal diet controls (p < 0.05). These HFD mice additionally did not upregulate SIRT3, and exhibited impaired wound healing compared with normal diet controls during the inflammatory phase of wound healing. Western blot analysis also revealed significantly elevated FABP4 and decreased SIRT3 protein levels in the HFD mice compared with normal diet controls. CONCLUSIONS: FABP4 appears to inhibit SIRT3 expression, which is important in macrophages for normal wound healing. In wound macrophages of diabetic mice, SIRT3 is decreased, likely in an FABP4-dependent mechanism. These results suggest an important role for FABP4 and SIRT3 in regulating inflammation in wound healing. A Mouse Hindlimb Gangrene Model after Novel Gene Therapy to Facilitate Reperfusion in Critical Limb Ischemia Punam P Parikh, MD, Roberta M Lassance-Soares, PhD, Manuela M Regueiro, PhD, Yan Li, Hongwei Shao, PhD, Zhao-Jun Liu, PhD, Omaida C Velazquez, MD, FACS University of Miami, Miami, FL INTRODUCTION: Lack of a reproducible hindlimb gangrene animal model limits pre-clinical treatment of critical limb ischemia (CLI). Our primary aim involved developing a gangrene model; the secondary aim involved testing the efficacy of E-selectin/ adeno-associated virus (AAV)-primed ischemic tissue for delay of hindlimb gangrene.
METHODS: To achieve gangrene, FVB mice underwent femoral artery ligation (FAL) with or without perioperative intra-peritoneal administration of NG-nitro-L-arginine methyl ester (LNAME), a nitric oxide synthase inhibitor. Gangrene-induced mice were administered LacZ+/AAV (control) or E-selectin/AAV (treatment) 4, 2, 0 days preoperatively. Gangrene was assessed using a standardized ischemia score from 0 (no gangrene) to 11 (forefoot gangrene), recorded on postoperative days (POD) 2, 7, and 14. Laser doppler imaging (LDI) quantified hindlimb reperfusion by mean perfusion of ligated: nonligated limb. Live animal dil perfusion quantified neovascularization in limb ischemia. Immunofluorescence verified E-selectin transgene expression. RESULTS: Most FVB did not develop gangrene with FAL-only (n ¼ 2/8, 25% gangrene incidence) but with FAL and LNAME (n ¼ 14/14, 100% gangrene incidence). Mean limb ischemia scores on POD 2,7,14 for LacZ+/AAV (n ¼ 7) and E-selectin/AAV (n ¼ 7) were 2.7, 3.9, and 5.3 vs 1.9, 2.9, and 3.7 (p ¼ 0.104). LDI on POD 7 for LacZ+/AAV and E-selectin/AAV was 0.27 vs 0.41 (p ¼ 0.071), POD 14 was 0.29 vs 0.54 (p ¼ 0.017). Dil perfused ligated hindlimb in LacZ+/AAV vs E-selectin/AAV revealed a mean neovascularization intensity score of 27.4 vs 35.3 (p ¼ 0.028). Immunofluorescence confirmed highly effective E-selectin/AAV gene delivery in treatment vs control limbs. CONCLUSIONS: Our reproducible murine gangrene model can be utilized to further understand Redox pathways contributing to gangrene. Intramuscularly transduced pro-angiogenic factors may facilitate neovascularization and limb reperfusion, accelerating CLI healing. Aortic Anatomic Severity Grade Correlates with Perioperative and Mid-Term Mortality in Patients Undergoing Abdominal Aortic Aneurysm Repair Zane Young, MD, Khurram Rasheed, MD, Antoinette Esce, Jennifer L Ellis, MD, Roan Glocker, MD, FACS, Adam J Doyle, MD, Kathleen G Raman, MD, FACS, Michael C Stoner, MD, FACS University of Rochester Medical Center, Rochester, NY INTRODUCTION: Anatomic severity grade (ASG) can be used preoperatively to provide a quantitative measure of abdominal aortic aneurysm (AAA) anatomic complexity, which we have previously demonstrated to correlate with value of repair. We proposed that ASG can be utilized to risk stratify patients undergoing AAA repair in the perioperative and mid-term periods. METHODS: This is a single institution retrospective review of patients who underwent AAA repair over a 7-year period. ASG scores were calculated manually using 3-dimensional reconstruction software by 2 blinded reviewers. Statistical analysis performed using multivariate statistics examining patient, pharmacologic, surgical, and anatomic variables. RESULTS: A total of 402 patients underwent AAA repair with complete anatomical and survival data. Mean ASG and age at
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http://dx.doi.org/10.1016/j.jamcollsurg.2017.07.488 ISSN 1072-7515/17
Vol. 225, No. 4S1, October 2017
the time of repair were 16 0.15 and 73 0.43 years old, respectively. Thirty-day mortality was 2.5% (n ¼ 10) and significantly associated with ASG >18, female sex, diabetes mellitus (DM), end-stage renal disease (ESRD), neoplasms, and aspirin use (p < 0.05). Statins were protective (p ¼ 0.004). Five-year mortality was 56.0% (n ¼ 225) and significantly associated with ASG > 15 (Figure), hyperlipidemia (HLD), coronary artery disease (CAD), ESRD, and COPD (p < 0.05). Excluding perioperative mortalities, ASG > 15 remained predictive of 5-year mortality (p ¼ 0.017).
CONCLUSIONS: Increasing aortic anatomic complexity correlates with perioperative and midterm mortality. Perioperatively, female sex, DM, and neoplasms were significant risk factors. Midterm mortality is associated with CAD, HLD, and COPD. ESRD confers an increased risk in both groups. These are the first data demonstrating a correlation between aortic anatomy and perioperative and midterm survival, suggesting a role for ASG in risk models. Aortobiilliofemoral Remote Endarterectomy for Aortoiliac Occlusive Disease: A Compelling Alternative to Bypass Zach M Feldman, Adam H Korayem, MD, PhD, Rajiv K Chander, MD, David J Finlay, MD, FACS Icahn School of Medicine at Mount Sinai, New York, NY INTRODUCTION: Aortobifemoral bypass is a durable surgery for aortoiliac occlusive disease (AIOD), restoring lower extremity blood flow. However, the potential for significant complications exists, impacting morbidity and mortality. Remote endarterectomy offers an alternative approach, avoiding many complications while demonstrating excellent results. METHODS: A single-institution consecutive case series of 8 patients with AIOD who were treated combining direct and remote endarterectomy. Standard small, bilateral femoral cut-downs and retroperitoneal infrarenal aortic approaches were followed by limited longitudinal aortic and proximal common iliac arteriotomies. Open aortic and proximal right common iliac thromboendarterectomy were performed, followed by bilateral femoral circumferential endarterectomies, leaving plaque intact and
Scientific Forum Abstracts
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contiguous with iliac disease. Core material was removed using a Volmar ring passed proximally into the aorta under manual intra-abdominal guidance (Figure). Direct femoral endarterectomies were completed, and all vessels were flushed and closed. RESULTS: Population mean age was 59.1 years, 88% were male, 75% were hypertensive, 100% had smoking history, and 38% had prior peripheral arterial disease intervention. Revascularization was achieved in all cases, with average ankle-brachial indices improving from 0.42 to 0.92 postoperatively (0.91 at 8-month follow-up). Six-year patency rates were 100%, with no reinterventions required. No MIs, strokes, deaths, amputations, intestinal ischemia, aortocaval and aortoenteric fistula development, sexual dysfunction, or aneurysmal degeneration were observed.
CONCLUSIONS: Aortobiiliofemoral remote endarterectomy is an effective alternative to aortobifemoral bypass for AIOD. Patency rates of 100% were achieved for this case series, with no postoperative complications or morbidities seen with the use of prosthetic grafts. Arterial Eversion Is a Safe Technique for Redo and Primary Carotid Endarterectomy Isibor J Arhuidese, MD, MPH, Jeffrey Edwards, MD, Danielle T Fontenot, MD, Inkyong K Parrack, MD, Peter R Nelson, MD, FACS, Brad Johnson, MD, Mahmoud Malas, MD, FACS, Murray L Shames, MD, FACS University of South Florida, Tampa, FL, Johns Hopkins Medical Institutions, Baltimore, MD INTRODUCTION: There is a constant challenge to identify targets for improvement of outcomes of carotid endarterectomy (CEA). This study evaluates outcomes of eversion and conventional CEA techniques in a large contemporary cohort of patients, with a goal to identify the relative safety of either procedure in the contexts of redo and primary surgery. METHODS: We studied all patients in the Vascular Quality Initiative (VQI) database who underwent eversion CEA (E-CEA) or conventional CEA (C-CEA) between January 2003 and September 2016. Univariable and multivariable chi-square, logistic and Cox regression analyses were performed, adjusting for patient