A randomized comparison of a 3-week and 6-week vascular surgery simulation course on junior surgical residents' performance of an end-to-side anastomosis.

OBJECTIVE: We assessed the effect of an open vascular simulation course on the surgical skill of junior surgical residents in performing a vascular end-to-side anastomosis and determined the course length required for effectiveness. We hypothesized that a 6-week course would significantly increase the surgical skill of junior residents in performing an end-to-side anastomosis, while a 3-week course would not. METHODS: We randomized 37 junior residents (postgraduate year 1 to 3) to a course consisting of three (short course, n = 18) or six (long course, n = 19) consecutive weekly 1-hour teaching sessions. Content focused on instrument recognition and performance of an end-to-side vascular anastomosis using a simulation model. A standardized 50-point vascular skills assessment (SVSA) measured knowledge and technical proficiency. Senior residents (postgraduate year 4 to 5) were tested at baseline. Junior residents were tested at baseline and at 1 and 16 weeks after course completion, and their scores were compared with baseline and senior resident scores. Residents and faculty completed a standardized anonymous evaluation of the course. RESULTS: Baseline scores between short-course and long-course participants were not different. At baseline, junior residents had significantly lower SVSA scores than senior residents (36±7 vs 41.4±2.5; P=.002). One week after course completion, SVSA scores for short-course (43.5±2.9 vs 34.2±7.5; P=.008) and long-course (43.9±5.6 vs 38.3±5.9; P=.006) participants were significantly improved from baseline. SVSA scores decreased slightly at 16 weeks but remained above baseline in short-course (39±6.2 vs 34.2±7.5; P=.03) and long-course (40±4.5 vs 38.3±5.9; P=.08) participants. Long vs short course length did not affect improvement in SVSA scores at 1 or 16 weeks. In short-course and long-course participants, SVSA scores at 1 and 16 weeks were not significantly different from senior resident scores. Course ratings were high, and 95% of residents indicated the course "made them a better surgeon." Residents and faculty felt the educational benefit of the course merited the investment of resources. CONCLUSIONS: An open vascular simulation course consisting of three weekly 1-hour sessions increased the surgical skill of junior residents in performing a vascular end-to-side anastomosis to that of senior residents on a standardized assessment. A 6-week course provided no additional benefit. This study supports the use of an open vascular simulation course to teach vascular surgical skills to junior residents. A course consisting of three 1-hour sessions is an effective and efficient component of a simulation program for junior surgical residents in a busy surgical center.

Interleukin 18 binding protein (IL18-BP) inhibits neointimal hyperplasia after balloon injury in an atherosclerotic rabbit model.

OBJECTIVES: Interleukin 18 (IL18) is an interferon (IFN)-gamma-inducing factor and a proinflammatory and proatherogenic cytokine. IL18 binding protein (IL18-BP) functions as an IL18 inhibitor. This study was designed to investigate whether systemic administration of IL18-BP could inhibit neointimal hyperplasia and arterial lipid deposition. METHODS: New Zealand white, male rabbits were fed with a 21% fat, 0.15% cholesterol diet. The left superficial femoral artery (SFA) was de-endotheliazed with a 2F arterial embolectomy catheter. IL18-BP (5 microg, 10 microg, or 25 microg), or 0.9% saline (control) was administered by i.v. bolus during surgery. Rabbits were followed-up at 2 and 4 weeks. Intima-media (I/M) and lumen-whole artery (L/A) area ratios, and luminal areas were measured. Serum lipid levels, liver enzymes, and kidney function were evaluated. Inflammatory cells were quantified and further verified with immunohistofluorescence staining. The extent of lipid deposition in the artery wall was quantified with Oil Red O (ORO) staining employing Zeiss AxioVision 4.6.3. Image analysis software. Lipid laden cells including macrophages were evaluated by transmission electron microscopy (TEM). RESULTS: Intravenous IL18-BP 5 microg, 10 microg, and 25 microg significantly reduced I/M ratios compared with the control group at both 2 and 4 weeks. There was no significant difference between the 5 microg and 10 microg dose groups. However, at 10 microg, IL18-BP significantly increased L/A ratio more than either the 5 microg IL18-BP or control groups. The high fat diet caused significant elevation of serum lipids at 4 and 6 weeks. IL18-BP had no effect on blood lipid levels. Lipid deposit in the thoracic aorta of the control group at 6 weeks was more than at 4 weeks (P = .025). Administration of IL18-BP inhibited the lipid deposition at 4 weeks (not significant) and 6 weeks (P = .012 to .008) compared with its control group. Lipid laden macrophages (foam cells), as well as endothelial cells and smooth muscle cells were seen in the descending thoracic aorta after 6 weeks of a high fat diet by ORO, immunohistofluorescence staining, and TEM. The lipid laden cells were not seen in either of IL18-BP groups. IL18-BP 10 microg significantly inhibited mono/macro adherence and infiltration in the SFA after balloon-injury at 2 weeks after surgery. CONCLUSION: A single intravenous dose of IL18-BP significantly decreased arterial neointimal hyperplasia, improved lumen to artery ratio after balloon-injury and also prevented arteriosclerosis progression. CLINICAL RELEVANCE: A single intravenous dose of IL18BP decreased neointimal hyperplasia and improved arterial L/A ratios in an atherosclerotic balloon-injury animal model. These preliminary results suggest that IL18BP may be a promising molecular approach to inhibit neointimal hyperplasia and arteriosclerosis progression following coronary and peripheral angioplasty.

Inhibition of experimental neointimal hyperplasia by recombinant human thrombomodulin coated ePTFE stent grafts.

OBJECTIVES: The goal of this study was to evaluate the ability of recombinant human thrombomodulin (rTM) to inhibit neointimal hyperplasia when bound to expanded polytetrafluoroethylene (ePTFE) stent grafts placed in a porcine balloon injured carotid artery model. METHODS: The left carotid artery of male pigs, weighing 25 to 30 Kg, was injured with an angioplasty balloon. Two weeks later either a non-coated standard ePTFE stent graft (Viabahn, 6 x 25 mm, W. L. Gore & Associates) or a rTM coated stent graft was implanted into the balloon-injured segment using an endovascular technique. Carotid angiography was performed at the time of the balloon injury, two weeks later and then at 4 weeks to assess the degree of luminal stenosis. One month after stent graft deployment, the grafts were explanted following in situ perfusion fixation for histological analysis. The specimens were then cross-sectioned into proximal, middle and distal segments, and the residual arterial lumen and intimal to media (I/M) ratios were calculated with computerized planimetry. RESULTS: rTM binding onto ePTFE-grafts was confirmed by functional activation of protein C and histopathology with immuno-scanning electron microscopy, backscatter electron emission imaging and x-ray microanalysis. All seven of the rTM coated stent grafts and six of the seven uncoated stent grafts were patent at the time of explantation. The mean luminal diameter of the rTM coated stents was 93% +/- 2.0% of the original diameter, compared with 67% +/- 23% (P = .006) in the control group. Histological analysis demonstrated that the area obliterated by intimal hyperplasia at the proximal portion of the rTM stent was -27% compared with the control group: (2.73 +/- 0.69 mm(2), vs 3.47 +/- 0.67 mm(2), P <.05). CONCLUSIONS: Neointimal hyperplasia is significantly inhibited in ePTFE stent grafts coated with rTM compared with uncoated grafts, as documented by improved luminal diameter by angiography and by computerized planimetry measurements of residual lumen area. These findings suggest that binding of recombinant human thrombomodulin onto ePTFE grafts may improve the long-term patency of covered stents grafts. CLINICAL RELEVANCE: Decrease of neointimal hyperplasia of the magnitude observed in this study could significantly improve blood flow and patency of small caliber prosthetic grafts. If the durability of these results can be confirmed by long-term studies, this technique may prove useful in preventing graft stenosis and arterial thrombosis following angioplasty or vascular bypass procedures.

The midterm results of stent graft treatment of thoracic aortic injuries.

INTRODUCTION AND OBJECTIVES: Several publications document the technical feasibility of stent graft repair of aortic transection. We report our mid-term results of endovascular repair of thoracic aortic transections using covered stent grafts and compare this to a cohort undergoing open repair during the same time period to demonstrate the shift in practice pattern at our institution. MATERIALS AND METHODS: A retrospective review of patients who sustained blunt thoracic transection was undertaken. Medical records were examined to identify the clinical outcome of the procedure, and follow-up CT scans were reviewed to document adequate treatment of the transection. Outcome measures include procedure-related mortality, neurological morbidity, and successful immediate and mid-term coverage of the thoracic false aneurysm and absence of graft migration or endoleak. RESULTS: From July, 2000 to October, 2004, 27 patients were identified with descending thoracic aortic transection at our level I trauma center. Fourteen patients were managed nonoperatively, five patients underwent thoracotomy and direct aortic repair, and eight patients underwent endoluminal stent graft repair. Of the endovascular group (n=8), repairs were performed with stacked AneuRx aortic cuffs (Medtronic, Inc., Minneapolis, MN) (n = 6), a Gore thoracic aortic stent graft (Thoracic EXCLUDER; W.L. Gore, Flagstaff, AZ) (n=1), or a Medtronic Talent thoracic endograft (Medtronic, Inc.) (n=1). Access for stent graft deployment was the common femoral artery (n=2), iliac artery (n=4), or distal abdominal aorta (n=2). Completion arch aortography and postoperative CT scanning confirmed successful management of the aortic transection in each patient. There were no procedure-related deaths, paraplegia, or stroke. Postoperative complications included a brachial artery thrombosis in one patient as well as an external iliac artery dissection and acute renal failure in a second patient for a complication rate of 37.5%. Two patients died as a result of their injuries unrelated to the stent graft repair. Mean follow-up of 16.6 mo has shown no evidence of endoleak or stent graft migration. Of the open repair group (n=5), one patient died in the operating room during attempted aortic repair, and one patient had a postoperative stroke. CONCLUSIONS: Due to technical success and absence of delayed complications including endoleak and graft migration, stent graft repair of traumatic aortic transection has replaced open aortic repair as the primary treatment modality in the multiply injured trauma patient at our institution. The postoperative complication rate observed in this small series tempers the success to some degree, but the severity of the complications compares favorably with those observed in the open repair group.

Temporal evolution of gene expression in rat carotid artery following balloon angioplasty.

The success of vascular intervention including angioplasty, stenting, and arterial bypass remains limited by negative remodeling resulted in lumen restenosis. This study was to characterize the global transcription profile reflecting concurrent events along arterial remodeling and neointima formation in a rat carotid artery balloon-injury model. Expression profiling of injured and control common carotid arteries on days 4, 7, 14 post-injury that mark the major pathohistological progression stages of neointimal formation were recorded on high-density oligonucleotide arrays. A subset of genes from microarray-based data was further studied using quantitative real time RT-PCR and in situ hybridization with sequential arterial samples from days 1 to 28 post-injury. The gene-encoded proteins were validated with Western blot. Besides temporal induction of a large cluster of genes over-represented by cell proliferation and macromolecule metabolism gene ontology categories, a fast-evolving inflammation could be demonstrated by the induction of Tgfb and other anti-inflammatory genes (e.g., C1qtnf3 (C1q and tumor necrosis factor related protein 3 (predicted))) and a shift from type 1 to 2 helper T cell response. The most significant signature of the induced neointimal profile is enrichment of genes functionally related to angiogenesis and extracellular matrix (ECM) remodeling (e.g., Spp1 (secreted phosphoprotein 1), CD44 (CD44 antigen), and Cxcl12 (chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1)). Some of the genes represent stress-responsive mesenchymal stromal cell cytokines. This study highlighted mesenchymal stromal cell cytokines-driven inflammatory extracellular matrix remodeling, as target processes for potential clinical therapeutic intervention.

Recombinant human thrombomodulin inhibits arterial neointimal hyperplasia after balloon injury.

OBJECTIVE: Smooth muscle cell proliferation is a major pathophysiologic factor in injury-induced neointimal hyperplasia and recurrent stenosis. We have demonstrated that recombinant human thrombomodulin (rTM) inhibits thrombin-induced arterial smooth muscle cell proliferation in vitro. The purpose of this study was to investigate the effect of rTM on neointimal hyperplasia in vivo. METHODS: A rabbit femoral artery balloon injury model was used. Bilateral superficial femoral arteries were deendothelialized with a 2F arterial embolectomy catheter. rTM (145 microg/kg; 2.0 microg/mL in circulation) or Tris-hydrochloride vehicle control was administered intravenously during the procedure, then either discontinued (group A) or administered twice daily for an additional 48 hours (group B). Rabbits were euthanized at 4 days and at 1, 2, and 4 weeks, and femoral artery specimens were prepared with in situ perfusion fixation and paraffin embedding. Luminal, intima, media, and whole artery areas were quantitated with digital imaging computerized planimetry. Intima-media and lumen-whole artery ratios were calculated. The injury-induced inflammatory reaction was also evaluated with light microscopy, scanning and transmission electron microscopy, and immunohistochemical and immunohistofluorescence staining. RESULTS: In the buffer control group, neointimal hyperplasia after femoral artery balloon injury was evident at 2 weeks, and was pronounced at 4 weeks (P <.0001). Infusion of rTM significantly inhibited intimal hyperplasia at both 2 and 4 weeks (P <.0001). In group A, rTM reduced the intima-media ratio by 27% and 39% at 2 and 4 weeks, respectively. Extended administration of rTM (group B) resulted in inhibition of hyperplasia by 57% and 30% at 2 and 4 weeks, respectively, but failed to reach significance compared with the shorter exposure. rTM infusion significantly inhibited thrombosis (8.1-fold) compared with the buffer control group (P =.012). rTM had no significant effect on lumen area or lumen-whole artery ratio, but treated arteries demonstrated significantly less compensatory dilatation (P =.045), as measured by whole artery area in response to less intimal hyperplasia. rTM administration inhibited platelet adhesion and inhibition of neutrophil infiltration to a degree that approached statistical significance (P =.0675). CONCLUSIONS: Systemic intravenous administration of rTM significantly decreases neointimal hyperplasia and improves patency in the rabbit femoral artery after balloon injury. In addition to exhibiting antithrombotic and antiproliferative effects, rTM may also invoke an anti-inflammatory mechanism, and may alter vascular remodeling in a multidimensional role to inhibit recurrent stenosis after arterial injury.

Management of hyperlipidemia in patients with vascular disease.

Atherosclerosis contributing to cardiovascular disease is the leading cause of death in the United States. It is also the major cause of peripheral arterial disease (PAD). Although there is substantial evidence that aggressive treatment of hyperlipidemia improves the outcome of patients with coronary artery disease (CAD), relatively little attention has been directed toward lipid control in patients with PAD. The National Cholesterol Education Program (NCEP) has established guidelines for treatment of lipids in patients with atherosclerotic disease. The purpose of this study was to determine the effectiveness of current lipid management practices in patients electively admitted for peripheral vascular surgery and to explore methods to improve compliance with NCEP guidelines. The past medical/surgical history, risk factors for atherosclerosis, and medication regimen including lipid medications were obtained from a retrospective review of the medical records of 105 consecutive patients scheduled for an elective vascular procedure. Lipid profiles were obtained as part of their routine preoperative assessment and the results were compiled and compared with established NCEP guidelines to determine the level of compliance in our PAD population. Eighty-five of the 105 patients had lipid profiles recorded in the medical record. Only 42% of patients were at or below the recommended goal of less than 100 mg/dL for low-density lipoprotein (LDL). Greater than half of patients had previous diagnosis of atherosclerosis or had previous bypass including coronary artery bypass surgery. Despite the strong emphasis on lipid reduction, especially LDL cholesterol, only a minority of patients admitted for peripheral vascular surgery were at the recommended NCEP goal. More aggressive evaluation and treatment of lipid disorders in patients with PAD seems warranted.

Immobilization of human thrombomodulin to expanded polytetrafluoroethylene.

BACKGROUND: The success of synthetic grafts for vascular reconstruction remains limited by thrombosis and intimal hyperplasia. In addition to the well-described antithrombotic effects of thrombomodulin, we have demonstrated that recombinant human thrombomodulin (rTM) inhibits arterial smooth muscle cell proliferation induced by thrombin. This study investigated the binding of functional rTM to expanded polytetrafluoroethylene (ePTFE). METHODS: Immobilization of rTM was achieved by either (1) a direct coating or (2) a two-step binding process using a water-soluble condensing cross-reaction agent EDAC to modify the ePTFE surface followed by binding of rTM. The samples were then subjected to a tangential shaken wash. The evidence of bound rTM was evaluated by both morphologic and functional studies. RESULTS: SEM, BSI, and X-ray microanalysis identified that the two-step binding method resulted in significantly greater binding of rTM molecules to ePTFE pre- and post a 7-h wash than the direct coating method. With the two-step binding method rTM ranging from 0.25 to 12.5 microg immobilized to ePTFE-activated protein C (APC) in a concentration-dependent manner by more than 6000-fold compared to the buffer control (P < 0.04) and 50-85% more than direct coating (P < 0.004). With direct coating, the level of APC dropped significantly to near 40% of the preshaken level at 2 h and diminished to 26% at 7 h. Whereas, the level of APC with the two-step binding stabilized at 51 and 49% after being shaken 2 and 7 h, respectively. CONCLUSION: Functional rTM binding to ePTFE was significantly improved with a new two-step binding method.

Origin of the left anterior descending coronary artery from the pulmonary artery: An unusual cause of angina in a middle-aged woman.

A 48-year-old woman was admitted to our institution with angina pectoris and a systolic murmur. At cardiac catheterization, she was found to have an anomalous origin of the left anterior descending coronary artery from the pulmonary trunk. There was also an associated atrial septal defect and a bicuspid aortic valve.