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The corpus callosum (CC) is a bundle of approximately 180 million axons connecting homologous areas of the left and right cerebral cortex. Because CC projections are topographically organized, regional CC morphological abnormalities may reflect regional cortical developmental abnormalities. We assess the variance characteristics of three CC area measurement techniques by comparing a single midsagittal slice versus three slices (midsagittal plus one parasagittal on each side) and five slices (midsagittal plus two parasagittal on each side). CC images were partitioned into five subregions using the Hofer-Frahm scheme under the three methods and variance was examined via two complementary data sets. In the first, to control for intersubject variability, 12 scans were acquired from a single subject over the course of 3 h. In the second, we used scans from 56 healthy male volunteers between the ages of 10 and 27 years (mean=17.47, S.D.=3.42). Increasing the number of slices from one to three to five diminished the coefficient of variation (CV) within subregions and increased the power to detect differences between groups. A power analysis was conducted for the sample under each method to determine the sample size necessary to discern a given percent change (delta) ranging from 1 to 20% iteratively., (Published by Elsevier Ireland Ltd.)

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., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

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.

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 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.

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.

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.

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.

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.

Objective: The long-term results of Greenfield inferior vena cava (IVC) filter placement have been well documented in adults; however, similar data do not exist for pediatric patients. The potential for growth and the increased life expectancy in younger patients may contribute to a difference in the natural history of filters placed in children. The objective of this study was to evaluate the long-term outcome of pediatric patients with IVC filters., Methods: At the University of Massachusetts Memorial Medical Center, medical records and radiographs of patients 18 years old or younger at the time of IVC filter placement were reviewed. Follow-up data were obtained by interview, physical examination, and venous duplex ultrasound scanning., Results: A total of 15 IVC filters were placed in children 18 years old or younger between 1983 and 1999. In 10 patients the indications for IVC filter placement were lower-extremity deep venous thrombosis (DVT) and/or pulmonary embolism. In five patients, prophylactic filters were placed in the absence of DVT because of a high risk for the development of pulmonary embolism. Surgical exposure of the right internal jugular vein was used to place the first eight filters. The remainder were inserted percutaneously through the right internal jugular vein or the right common femoral vein. There were no complications or mortality related to filter insertion. Follow-up of the surviving 14 patients ranged from 19 months to 16 years. During long-term follow-up, no patient had a pulmonary embolus. Of the nine patients who had lower-extremity DVT, three developed mild common femoral venous reflux documented by duplex scan. Of the five patients who had prophylactic filters, four had no symptoms or duplex evidence of reflux. The other patient, who was paraplegic, had bilateral leg edema but no venous varicosities and no reflux on duplex scan 11 years after filter placement. No patient in either group had chronic venous obstruction., Conclusion: In long-term follow-up there were no instances of pulmonary embolism, IVC thrombosis, significant postphlebitic symptoms, or significant filter migration among 14 pediatric patients with Greenfield IVC filters. This suggests a safety profile and efficacy similar to that seen in adults.

Purpose: We performed a randomized, double-blind, placebo-controlled, multicenter trial to evaluate the relative efficacy and safety of cilostazol and pentoxifylline., Patients and Methods: We enrolled patients with moderate-to-severe claudication from 54 outpatient vascular clinics, including sites at Air Force, Veterans Affairs, tertiary care, and university medical centers in the United States. Of 922 consenting patients, 698 met the inclusion criteria and were randomly assigned to blinded treatment with either cilostazol (100 mg orally twice a day), pentoxifylline (400 mg orally 3 times a day), or placebo. We measured maximal walking distance with constant-speed, variable-grade treadmill testing at baseline and at 4, 8, 12, 16, 20, and 24 weeks., Results: Mean maximal walking distance of cilostazol-treated patients (n = 227) was significantly greater at every postbaseline visit compared with patients who received pentoxifylline (n = 232) or placebo (n = 239). After 24 weeks of treatment, mean maximal walking distance increased by a mean of 107 m (a mean percent increase of 54% from baseline) in the cilostazol group, significantly more than the 64-m improvement (a 30% mean percent increase) with pentoxifylline (P <0.001). The improvement with pentoxifylline was similar (P = 0.82) to that in the placebo group (65 m, a 34% mean percent increase). Deaths and serious adverse event rates were similar in each group. Side effects (including headache, palpitations, and diarrhea) were more common in the cilostazol-treated patients, but withdrawal rates were similar in the cilostazol (16%) and pentoxifylline (19%) groups., Conclusion: Cilostazol was significantly better than pentoxifylline or placebo for increasing walking distances in patients with intermittent claudication, but was associated with a greater frequency of minor side effects. Pentoxifylline and placebo had similar effects.

Purpose: Restenosis after angioplasty or bypass grafting to restore circulation to ischemic organs is still an unsolved problem. Thrombin generated in high concentrations at the sites of vascular injury plays a central role in thrombosis and hemostasis. alpha-Thrombin has also been implicated as a mitogen for smooth muscle cell (SMC) proliferation that contributes to arterial restenosis. Thrombomodulin has a high affinity of binding with thrombin and converts thrombin from a procoagulant to an anticoagulant. This study was designed to examine whether thrombomodulin could also moderate the thrombin-mediated SMC proliferative response., Methods: Porcine carotid artery SMCs (passages 4-7) were plated onto 96-well plates and incubated for 3 days. After growth arrest in a defined serum-free medium for 2 to 3 days, SMCs were subjected to the reagents as follows: (1) human alpha-thrombin, (2) recombinant human soluble thrombomodulin containing a chondroitin sulfate moiety, (3) thrombin receptor agonist peptide (SFLLRNPNDKYEPF), and (4) alpha-thrombin or thrombin receptor agonist peptide combined with recombinant thrombomodulin (rTM). The viability and proliferation status of SMCs were quantified with MTT (thiazolyl blue) mitochondrial function and bromodeoxyuridine (BrdU)-DNA incorporation assays., Results: Human alpha-thrombin increased SMC proliferation in a dose dependent manner by more than 25% and 30% with thrombin 1 U/mL to 3 U/mL compared with control groups on day 7 (P <.006). rTM concentrations from 0.5 microg/mL to 3 microg/mL have no significant effect on SMC growth. The stimulation of SMC proliferation induced by alpha-thrombin at 0.5 U/mL, 1 U/mL, and 2 U/mL was significantly inhibited with rTM at 2 microg/mL and 3 microg/mL on days 3, 7, and 10 as evaluated with MTT assay (P <.01 to <.05) and BrdU-DNA incorporation assay on day 3 (P <.008). Thrombin receptor agonist peptide increased SMC BrdU-DNA incorporation at 48 hours (P <.007), and its effect was not altered by rTM., Conclusion: rTM containing all of the extracellular domains of thrombomodulin inhibits the effect of thrombin on SMC proliferation in vitro. Because thrombin is a mitogenic mediator of SMC in vascular injury, inhibition of its function in vivo could help to prevent SMC hyperplasia. The success of further studies in vivo may lead to use of rTM for decreasing or preventing arterial restenosis.

Background: Effective medication is limited for the relief of intermittent claudication, a common manifestation of arterial occlusive disease. Cilostazol is a potent inhibitor of platelet aggregation with vasodilation effects., Objective: To evaluate the safety and efficacy of cilostazol for the treatment of intermittent claudication., Methods: Thirty-seven outpatient vascular medicine clinics at regional tertiary and university hospitals in the United States participated in this multicenter, randomized, double-blind, placebo-controlled, parallel trial. Of the 663 screened volunteer patients with leg discomfort, a total of 516 men and women 40 years or older with a diagnosis of moderately severe chronic, stable, symptomatic intermittent claudication were randomized to receive cilostazol, 100 mg, cilostazol, 50 mg, or placebo twice a day orally for 24 weeks. Outcome measures included pain-free and maximal walking distances via treadmill testing, patient-based quality-of-life measures, global assessments by patient and physician, and cardiovascular morbidity and all-cause mortality survival analysis., Results: The clinical and statistical superiority of active treatment over placebo was evident as early as week 4, with continued improvement at all subsequent time points. After 24 weeks, patients who received cilostazol, 100 mg, twice a day had a 51% geometric mean improvement in maximal walking distance (P<.001 vs placebo); those who received cilostazol, 50 mg, twice a day had a 38% geometric mean improvement in maximal walking distance (P<.001 vs placebo). These percentages translate into an arithmetic mean increase in distance walked, from 129.7 m at baseline to 258.8 m at week 24 for the cilostazol, 100 mg, group, and from 131.5 to 198.8 m for the cilostazol, 50 mg, group. Geometric mean change for pain-free walking distance increased by 59% (P<.001) and 48% (P<.001), respectively, in the cilostazol, 100 mg, and cilostazol, 50 mg, groups. These results were corroborated by the results of subjective quality-of-life assessments, functional status, and global evaluations. Headache, abnormal stool samples or diarrhea, dizziness, and palpitations were the most commonly reported potentially drug-related adverse events and were self-limited. A total of 75 patients (14.5%) withdrew because of any adverse event, which was equally distributed between all 3 treatment groups. Similarly, there were no differences between groups in the incidence of combined cardiovascular morbidity or all-cause mortality., Conclusion: Compared with placebo, long-term use of cilostazol, 100 mg or 50 mg, twice a day significantly improves walking distances in patients with intermittent claudication.

Background: Adenosine is a potent vasodilator of vascular smooth muscle. Endothelium-derived nitric oxide (NO) elicits vasodilation. We have previously reported that adenosine stimulates the production of NO from porcine carotid arterial endothelial cells (PCAEC) via a receptor-mediated mechanism. This study was to determine whether adenosine also enhances NO production from human arterial endothelium and to define the involvement of adenosine A1 and A2 receptors., Materials and Methods: Human iliac arterial endothelial cells (HIAEC) and PCAEC were harvested and cultured in dishes. NO production was evaluated with a NO electrode sensor which measured continuously real-time NO production., Results: NO content of the medium bathing HIAEC and PCAEC was significantly increased with adenosine (100 micromol/L). Ethylcarboxamidoadenosine (NECA), a nonselective adenosine receptor agonist, and carboxyethyl-phenethylamino-ethylcarboxamidoadenosine (CGS-21680), a selective adenosine A2a receptor agonist, increased NO production by HIAEC and PCAEC with respective EC50 values of 3.32 and 6.96 nmol/L for NECA and 30.97 and 29.47 nmol/L for CGS-21680. Chlorofuryl-triazolo-quinazolinamine (CGS-15943; 1 micromol/L), an adenosine A1 and A2 receptor antagonist, and aminofuryltriazolotriazinyl-aminoethylphenol (ZM-241385; 1 micromol/L), a selective adenosine A2a receptor antagonist, inhibited the effect of CGS-21680. Chlorocyclopentyl-adenosine (CCPA; 1 micromol/L), an adenosine A1 receptor agonist, significantly depressed NO production by both HIAEC and PCAEC: This effect was inhibited by cyclopentyl-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist., Conclusions: The results demonstrate that adenosine A2a receptors increase, and adenosine A1 receptors decrease, the production of NO by human and porcine arterial endothelial cells., (Copyright 1998 Academic Press.)

Background: Cilostazol is a new phosphodiesterase inhibitor that suppresses platelet aggregation and also acts as a direct arterial vasodilator. This prospective, randomized, placebo-controlled, parallel-group clinical trial evaluated the efficacy of cilostazol for treatment of stable, moderately severe intermittent claudication., Methods and Results: Study inclusion criteria included age > or =40 years, initial claudication distance (ICD) on treadmill (12.5% incline, 3.2 km/h) between 30 and 200 m, and confirmation of diagnosis of chronic lower-extremity arterial occlusive disease. After stabilization and single-blind placebo lead-in, 81 subjects (62 male, 19 female) from 3 centers were randomized unequally (2:1) to 12 weeks of treatment with cilostazol 100 mg PO BID or placebo. Primary outcome measures included ICD and maximum distance walked (absolute claudication distance, or ACD). Secondary outcome measures included ankle pressures, subjective assessments of benefit by patients and physicians, and safety. Treatment and control groups were similar with respect to age, severity of symptoms, ankle pressures, and smoking status. Statistical analyses used intention-to-treat analyses for each of 77 subjects who had > or =1 treadmill test after initiation of therapy. Comparisons between groups were based on logarithms of ratios of ICD and ACD changes from baseline using ANOVA test at last treatment visit. The estimated treatment effect showed a 35% increase in ICD (P<0.01) and a 41% increase in ACD (P<0.01). There was no significant change in resting or postexercise ankle/brachial indexes. Patients' and physicians' subjective assessments corroborated the measured improvements in walking performance observed in the cilostazol-treated group., Conclusions: Cilostazol improved walking distances, significantly increasing ICD and ACD. The data suggest cilostazol is safe and well tolerated for the treatment of intermittent claudication.

Pneumonia is the most common serious complication of varicella infection in adults. A variety of thrombotic complications including purpura fulminans and disseminated intravascular coagulation have been reported in children with varicella but not in adults. Two men with varicella pneumonia who had profound lower extremity ischemia caused by thrombosis of the profunda femoris and tibial arteries are reported. Both patients had free protein S deficiency and vascular thrombosis in association with varicella pneumonia without overt evidence of disseminated intravascular coagulation or purpura fulminans. Antiphospholipid immunoglobulin G and immunoglobulin M antibodies were present in one, whereas the other had evidence of the lupus anticoagulant. The proposed pathogenesis and management options including intraarterial thrombolytic therapy with urokinase and the need for long-term anticoagulation are discussed.

Purpose: Because dipyridamole thallium (DT) scanning is a useful predictor of perioperative cardiac events, a positive results of a DT scan is frequently the basis for performing more invasive cardiac evaluation and for consideration for performing coronary revascularization procedures before performing peripheral vascular surgery. The rationale for this approach has been that the treatment of anatomically significant coronary artery disease would lower the risk of performing a subsequent vascular operation. However, the benefit of performing aggressive diagnostic and therapeutic cardiac procedures in such patients remains unproved. To examine this issue, data from patients who underwent coronary angiography because of thallium redistribution were compared with data from matched control subjects who underwent peripheral vascular operations without further cardiac evaluation., Methods: The medical records of 70 consecutive patients who underwent coronary angiography because of the presence of two or more segments of redistribution on DT scan were reviewed and compared with 70 other patients matched with respect to age, gender, peripheral vascular operation, and number of segments of redistribution on DT scan who did not undergo additional cardiac evaluation., Results: DT scans were performed on 934 preoperative peripheral vascular surgery patients to help in the assessment of operative risk. Ischemic responses, defined as two or more segments of redistribution, were observed in 297. Of these, 70 underwent cardiac catheterization and 25 underwent coronary revascularization procedures. Adverse outcomes affected 46% of the coronary angiography group and 44% of the control group (p = NS). Patients who underwent coronary angiography and were considered for myocardial revascularization had fewer cardiac events with a subsequent vascular operation than did the control subjects. However, any possible benefit from invasive cardiac evaluation was offset by the three deaths and two myocardial infarctions (MIs) that complicated the cardiac evaluation. There was no significant difference between the angiography group and the matched control subjects with respect to perioperative nonfatal MI (13% vs 9%), fatal MI (4% vs 3%), late nonfatal MI (16% vs 19%), or late cardiac death (10% vs 13%). In long-term follow-up, MIs occurred later in patients who underwent coronary angiography than the control subjects (p = 0.049), but this difference was not associated with an improvement in the overall survival rate., Conclusions: The risks of extended cardiac evaluation and treatment did not produce any improvement in either the perioperative or the long-term survival rate. For most vascular surgery patients who have a positive result of a DT scan, coronary angiography does not provide any additional useful information.

Heparin has been shown to decrease total vascular resistance while protamine stimulates endothelium-dependent vasodilation. This study was undertaken to determine whether heparin and/or protamine could enhance endothelium-derived relaxing factor (EDRF), as determined by nitric oxide (NO) production. Porcine carotid artery endothelial cells (PAECs) were seeded on multiwell plates, grown to confluence, and exposed to heparin (1-20 U/ml) or protamine (50-200 microg/ml) for 24 hours. With the addition of the NO synthase inhibitor, N(G)-monomethyl-L-arginine (NMMA), to heparin and/or protamine, the medium samples were collected in one hour. In a parallel clinical study, plasma samples were collected from patients undergoing cardiopulmonary bypass (CPB). The NO production was measured as reflected by the formation of nitrite (NO2-) and nitrate (NO3-), the stable end-metabolites of NO. NO production by PAECs was significantly increased by heparin > or = 5 U/ml or protamine > or = 50 microg/ml in a concentration-dependent manner. The increase of NO production was prevented by the addition of NMMA. In CPB patients, plasma NO2-/NO3- concentration was significantly increased after heparin administration compared to the preoperative value, at which time the mean plasma heparin level was 4.9+/-0.5 U/ml. Following slow protamine infusion, there was no significant difference in plasma NO2-/NO3- concentration compared to preoperative value. In conclusion NO production increases following exposure of PAECs to heparin and/or protamine. In patients, NO concentration significantly increased after heparin administration by IV bolus, but not with a slow infusion of protamine after CPB.

Objective: To evaluate the feasibility of surgical exposure of the full length of the left subclavian artery using a median sternotomy and left supraclavicular extension., Design: Anatomic study of five cadavers, and case review of four patients with blunt trauma to the proximal left subclavian artery., Materials and Methods: A median sternotomy with left supraclavicular extension was performed on five cadavers and four patients. The depth of various portions of the subclavian artery was measured. Photographs of the dissections were used to document anatomic relationships and to serve as a basis for pen and ink drawings. The hospital records of four patients in which this exposure was used were reviewed for operative details., Measurements and Main Results: The left subclavian artery was readily exposed from its origin on the aortic arch to its termination as the axillary artery in all cadaver dissections, including one who was more than 300% ideal body weight. The first portion of the subclavian artery lay at an average wound depth of 6.0 cm, with a mean length of 4.7 cm. The same surgical approach was used for the care of four patients who sustained blunt trauma to the first portion of the left subclavian artery and permitted expeditious control and excellent exposure for placement of a proximal subclavian interposition graft in two, a proximal subclavian to axillary artery graft in the third, and resection and end-to-end anastomosis in the fourth., Conclusions: Median sternotomy with left supraclavicular extension provides rapid, safe, and reliable exposure of all portions of the left subclavian artery without the morbidity associated with clavicular resection, thoracotomy, or a "trapdoor" incision. Furthermore, the ability to perform this procedure in the supine position allows access to the abdominal cavity, the neck, and the extremities, which often require concomitant operative intervention in a patient with multiple injuries.

Purpose: It is commonly believed that the incidence of deep venous thrombosis (DVT) in hospitalized children is less than in adults. However, it is possible that the disease is significantly underdiagnosed in children because the index of suspicion of pediatric practitioners is low, a substantial number of patients may have no symptoms, and DVT screening is not routinely performed. We therefore undertook a prospective study to define the incidence of DVT in hospitalized children with no symptoms., Methods: Patients included in the study were those younger than 18 years of age who were hospitalized for more than 72 hours and were identified to have two or more risk factors for the development of DVT and had at least one screening duplex scan. Risk factors for the development of DVT considered were a history of DVT or pulmonary embolism, recent operation, immobilization, trauma, stroke or acute neurologic deficit, the presence of cancer, sepsis, greater than 150% ideal body weight, a hypercoagulable state, and the presence of a femoral venous catheter., Results: Over the 9-month period ending December 1994, 1997 patients 17 years of age and younger were admitted to the hospital, and 59 patients including 19 girls and 40 boys were enrolled in the study. The one patient with DVT was a 17-year-old boy hospitalized after a motor vehicle accident with blunt head trauma and a neurologic deficit who underwent multiple orthopedic and neurosurgical procedures., Conclusions: The development of acute DVT in children is unusual. As a result, DVT prophylaxis and screening is unnecessary in young children with only two risk factors for the development of the disease. Young age appears to be an important protective risk factor for the prevention of DVT.

Objectives: This study sought to develop and validate a Bayesian risk prediction model for vascular surgery candidates., Background: Patients who require surgical treatment of peripheral vascular disease are at increased risk of perioperative cardiac morbidity and mortality. Existing prediction models tend to underestimate risk in vascular surgery candidates., Methods: The cohort comprised 1,081 consecutive vascular surgery candidates at five medical centers. Of these, 567 patients from two centers ("training" set) were used to develop the model, and 514 patients from three centers were used to validate it ("validation" set). Risk scores were developed using logistic regression for clinical variables: advanced age (>70 years), angina, history of myocardial infarction, diabetes mellitus, history of congestive heart failure and prior coronary revascularization. A second model was developed from dipyridamole-thallium predictors of myocardial infarction (i.e., fixed and reversible myocardial defects and ST changes). Model performance was assessed by comparing observed event rates with risk estimates and by performing receiver-operating characteristic curve (ROC) analysis., Results: The postoperative cardiac event rate was 8% for both sets. Prognostic accuracy (i.e., ROC area) was 74 +/- 3% (mean +/- SD) for the clinical and 81 +/- 3% for the clinical and dipyridamole-thallium models. Among the validation sets, areas were 74 +/- 9%, 72 +/- 7% and 76 +/- 5% for each center. Observed and estimated rates were comparable for both sets. By the clinical model, the observed rates were 3%, 8% and 18% for patients classified as low, moderate and high risk by clinical factors (p<0.0001). The addition of dipyridamole-thallium data reclassified >80% of the moderate risk patients into low (3%) and high (19%) risk categories (p<0.0001) but provided no stratification for patients classified as low or high risk according to the clinical model., Conclusions: Simple clinical markers, weighted according to prognostic impact, will reliably stratify risk in vascular surgery candidates referred for dipyridamole-thallium testing, thus obviating the need for the more expensive testing. Our prediction model retains its prognostic accuracy when applied to the validation sets and can reliably estimate risk in this group.

Normal circulating platelets do not adhere to intact, undisturbed endothelium. Studies have shown, however, that platelets will adhere to virally infected or thrombin-stimulated human umbilical vein endothelial cells. Using a novel platelet/endothelial cell adhesion assay we studied the interaction of thrombin-activated platelets to human saphenous vein endothelial cells (HSVEC), and its mechanism(s). Biotinylated platelets were exposed to Hepes-Tyrode buffer, 10E5 or PAC-1 [monoclonal antibodies (Mabs) blocking GPIIb-IIIa], AK4 (Mab blocking P-selectin, 6D1 (Mab blocking vWf binding to GPIb), RGDS (small peptide blocking the fibrinogen binding site), or EDTA (dissociates GPIIb-IIIa complex) and then activated with thrombin. The platelets were subsequently exposed to thrombin-stimulated monolayer HSVEC. Phycoerythrin-streptavidin was added to the wells to fluorescently label the platelets, followed by formaldehyde fixation and washing to remove nonadherent platelets. Adhesion of platelets to HSVEC was assessed using a fluorescent multiwell plate reader. Antibodies which blocked the GPIIb-IIIa receptor and agents which competitively bound the receptor all significantly inhibited activated platelet adhesion to the activated HSVEC. We have found that thrombin significantly increases platelet/HSVEC adhesion, and this event is mediated via the integrin GPIIb-IIIa (fibrinogen receptor). These GPIIb-IIIa receptor blocking Mabs and RGDS may be useful adjuncts for improving patency following angiographic intervention and/or vein grafting in patients with high risk of thrombosis. The assay we have developed is a valuable and relatively simple method for assessing platelet/endothelial cell adhesion and activation.

Purpose: Iatrogenic femoral pseudoaneurysms (IFP) have traditionally been treated surgically. Recently, this common problem has been successfully treated without operation by use of ultrasound-guided compression (UGC) to induce thrombosis of the false aneurysm cavity, but the risk factors for failure and the long-term outcome have not been defined., Methods: All patients referred to the vascular laboratory from June 1992 to November 1994 whose femoral pseudoaneurysms were treated by UGC were included in the study. Data were collected prospectively during the last 18 months of the study. Data regarding the location and morphologic characteristics of the pseudoaneurysms and anticoagulation status were documented. Patients who had successful UGC underwent follow-up duplex scanning and ankle-brachial arterial pressure evaluations., Results: Fifty-seven patients with IFP were treated with UGC over a 30-month period; the last 34 were evaluated prospectively. UGC was successful at obliterating the false aneurysm cavity with the initial attempt in 47 (83%). Thrombosis of seven additional pseudoaneurysms was achieved on subsequent UGC attempts for an overall success rate of 95%. Recurrent false aneurysms were noted in two patients 2 and 10 days after initially successful UGC. Both were treated successfully with repeat UGC. Multivariate analysis of 14 variables revealed heparin anticoagulation (chi-square 9.025, p = 0.001) as the only significant risk factor for failure of UGC. There were no episodes of arterial thrombosis, embolization, or femoral nerve injury associated with UGC. Temporary occlusion of femoral artery during UGC and compression intervals of 20 minutes were well tolerated. Long-term follow-up from 30 to 400 days after UGC was available in 36 patients. There was no late recurrence or significant change in ankle-brachial pressures (p > 0.05)., Conclusion: UGC is a safe and effective treatment for most catheter-induced femoral pseudoaneurysms with a low complication rate and excellent long-term results at a cost substantially lower than operative treatment. Because the natural history of IFP is unpredictable, UGC appears to be the preferred treatment for all IFPs persisting after cessation of heparin anticoagulation.

The incidence and sequelae of deep venous thrombosis (DVT) in trauma patients are unclear because the majority of patients who develop DVT are asymptomatic. This study evaluated the incidence, risk factors, and efficacy of prophylaxis for DVT in trauma patients over a 5-year period. Trauma patients at high risk for DVT were evaluated biweekly with lower extremity venous duplex scans. The DVT prophylaxis was instituted on admission with low-dose heparin therapy and pneumatic compression. The incidence of asymptomatic DVT identified by duplex screening was 10% (45 of 458); one pulmonary embolus occurred. Five variables were significant from bivariate and multiple logistic regression analysis: age (p = 0.005), Injury Severity Score (p = 0.005), length of stay (p = 0.004), Trauma and Injury Severity Score (p = 0.01), and spinal injury (p = 0.014). This analysis documents that trauma patients with these risk factors are at increased risk for the development of asymptomatic DVT, despite prophylaxis, and warrant surveillance with venous duplex sonography.

Background: Acute renal failure is common after repair of ruptured abdominal aortic aneurysm. Early dialysis has recently been advocated to reduce the mortality associated with multiorgan failure, but hemodialysis (HD) is not well-tolerated in critically ill patients because of hemodynamic instability and risk of bleeding from anticoagulation therapy. Peritoneal dialysis (PD) has the advantage in that it causes minimal cardiopulmonary instability and does not require anticoagulation. The presence of a freshly-closed abdominal wound and an aortic graft, however, have previously been considered to be contraindications to PD., Methods: Peritoneal dialysis catheters were placed in 69 of the 105 patients who underwent grafting for a ruptured abdominal aortic aneurysm between 1982 and 1993. Criteria for placement included shock, perioperative oliguria, and preoperative renal insufficiency. All charts were reviewed retrospectively to evaluate the safety and efficacy of placing PD catheters and initiating early dialysis in patients at risk for developing acute renal failure., Results: Acute tubular necrosis developed in 31 patients, 19 of whom required dialysis. Peritoneal dialysis alone provided effective dialysis in 8 patients, and it was combined with hemofiltration and/or HD in 9 additional patients for an overall efficacy of 58%. The peritoneal catheter also facilitated the early diagnosis of peritonitis due to colon ischemia in 5 patients, and was helpful in diagnosing intra-abdominal hemorrhage in 4 others. Bacterial peritonitis occurred in 3 (17%) patients undergoing PD with no cause noted for the infection diagnosing other than use of the PD catheter. A single aortic graft infection was diagnosed 4.2 years postoperatively with an enteric organism in a patient with recurrent diverticulitis. Two patients with peritoneal catheters developed abdominal wound dehiscence, but neither had undergone PD (P > 0.2). In a multivariate analysis, placement of a PD catheter did not affect survival., Conclusions: Placement of a PD catheter at the time of resection of a ruptured abdominal aortic aneurysm in patients at risk for development of acute renal failure is without significant complications and can facilitate early and effective dialysis. The peritoneal dialysis catheter may also be useful in making an early diagnosis of intraperitoneal bleeding and infection.

Adenosine per se is a potent vasodilator of vascular smooth muscle. Endothelial cells modulate vascular tone via the release of nitric oxide (NO), which also elicits vasodilation. This study was undertaken to determine whether adenosine could directly stimulate endothelial cells to enhance NO production, which could subsequently reduce vascular tone. NO production was evaluated in porcine carotid artery endothelial cells (PCAEC) and human saphenous vein endothelial cells (HSVEC) seeded on multiwell plates, grown to confluence, and treated with adenosine for 1 h. The bathing medium was collected, and the NO production was determined as reflected by the formation of NO2- and NO3-. NO production by PCAEC was significantly increased by adenosine in a dose-dependent manner, whereas there was only an insignificant tendency for an increase by HSVEC. The addition of the NO synthase competitive inhibitor, NG-monomethyl-L-arginine (NMMA), or the adenosine receptor antagonist, theophylline, prevented the increase in NO production by adenosine. The results suggest that adenosine stimulates, by a receptor-mediated mechanism, the production of NO by arterial, but not by venous, endothelial cells.

Purpose: The evaluation of coronary artery disease (CAD) in patients undergoing vascular surgery can provide information with respect to perioperative and long-term risk for CAD-related events. However, the extent to which the required surgical procedure itself imparts additional risk beyond that dictated by the presence of CAD determinants remains in question. The purpose of this study was to quantify the relative contributions of specific vascular procedures and CAD markers on perioperative and long-term cardiac risk., Methods: The study cohort comprised 547 patients undergoing vascular surgery from two medical centers who underwent clinical evaluation, dipyridamole thallium testing, and either aortic (n = 321), infrainguinal (n = 177), or carotid (n = 49) vascular surgery between 1984 and 1991. Perioperative and late cardiac risk of fatal or nonfatal myocardial infarction (MI) was compared for the three procedures before and after adjustment for the influence of comorbid factors. These adjusted estimates may be regarded as the component of risk because of type of surgery., Results: Perioperative MI occurred in 6% of patients undergoing aortic and carotid artery surgery, and in 13% of patients undergoing infrainguinal procedures (p = 0.019). Significant (p < 0.05) predictors of MI were history of angina, fixed and reversible dipyridamole thallium defects, and ischemic ST depression during testing. Although patients undergoing infrainguinal procedures exhibited more than twice the risk for perioperative MI compared with patients undergoing aortic surgery (relative risk: 2.4[1.2 to 4.5, p = 0.008]), this value was reduced to insignificant levels (1.6[0.8 to 3.2, p = 0.189]) after adjustment for comorbid factors. There was little change in comparative risk between carotid artery and aortic procedures before (1.0[0.3 to 3.6, p = 0.95]) or after (0.6[0.2 to 2.3, p = 0.4]) covariate adjustment. The 4-year cumulative event-free survival rate was 90% +/- 2% for aortic, 74% +/- 5% for infrainguinal, and 78% +/- 7% for carotid artery procedures (p = 0.0001). Predictors of late MI included history of angina, congestive heart failure, diabetes, fixed dipyridamole thallium defects, and perioperative MI. Patients undergoing infrainguinal procedures exhibited a threefold greater risk for late events compared with patients undergoing aortic procedures (relative risk: 3.0[1.8 to 5.1, p = 0.005]), but this value was reduced to 1.3(0.8 to 2.3, p = 0.32) after adjustment. Long-term risk among patients undergoing carotid artery surgery was less dramatically altered by risk factor adjustment., Conclusion: In current practice, among patients referred for dipyridamole testing before operation, observed differences in cardiac risk of vascular surgery procedures may be primarily attributable to readily identifiable CAD risk factors rather than to the specific type of vascular surgery. Thus the cardiac and diabetic status of patients should be given careful consideration whenever possible, regardless of surgical procedure to be performed.

Purpose: The purpose of this study was to evaluate the long-term safety and efficacy of the titanium Greenfield filter-modified hook for prevention of pulmonary embolism., Methods: We conducted a prospective study in 173 patients from four institutions who underwent clinical examination, abdominal radiography, and duplex ultrasound examinations of the vena cava and lower extremities. If indicated by protocol or clinical presentation, computed tomography scans, pulmonary angiograms, or venacavograms were obtained., Results: The most common procedural event was filter limb asymmetry (10%), which had no clinical significance. A variety of other minor procedural events occurred in another 10% of cases. Early follow-up (< 6 months) was completed in 149 patients, and long-term evaluation was completed in 113 (> 12 months). Deaths in 24 patients were from nonembolic causes in all but one. There were four suspected or confirmed recurrent pulmonary emboli, for an incidence of 3.5% (four of 113), with one death (0.9%). Four patients had inferior vena cava occlusion at early follow-up and at long-term evaluation, only one remained occluded (1%). Insertion site venous thrombosis was seen in only two patients (2%)., Conclusion: The titanium Greenfield filter provides protection comparable to the standard stainless steel Greenfield filter after 1 year with a low incidence of recurrent pulmonary embolism (3.5%) and a high caval patency rate (99%).

The effect of endothelial cell seeding on the patency of small-caliber expanded polytetrafluoroethylene (ePTFE) grafts used for venous replacements in a canine experimental model was evaluated. Grafts were implanted bilaterally in 12 dogs as femoral vein interpositions. In each animal, one graft was seeded with enzymatically derived homologous endothelial cells which had been cultivated for 3 days in vitro before implantation, whereas the contralateral graft was not seeded. In five dogs, venography was performed at 2 weeks, and grafts were then excised. In the remaining seven dogs, venography was performed at both 2 and 4 weeks, with graft excision at 4 weeks. Graft patency at 2 weeks for seeded grafts was 75% (nine of 12) compared with only 33% (four of 12) for unseeded grafts (P < 0.02). There were no new episodes of thrombotic occlusion between 2 and 4 weeks. Five dogs with thrombus in the control graft did not develop thrombus in the contralateral seeded graft. Furthermore, each dog with a patent control graft had no thrombus in the seeded graft. It is concluded that the early patency of seeded ePTFE grafts is superior to that of unseeded ePTFE grafts in the femoral vein.

Dipyridamole thallium scintigraphy has previously been shown to have prognostic value in the preoperative assessment of patients scheduled to undergo vascular surgery, but its effect on the long-term outcome is less well-defined. In the largest series to date, dipyridamole thallium scanning was performed in 360 patients before elective vascular surgery and survivors were followed for a mean of 31 months. In the 327 patients who underwent vascular surgery, operative death and nonfatal myocardial infarction occurred in 4.9 and 6.7%, respectively. A cardiac event (nonfatal myocardial infarction or cardiac death) occurred in 14.4% of patients with a transient thallium defect, as opposed to 1% with a normal scan (p < 0.001). Logistic regression analysis revealed that the best predictor of a perioperative event was the presence of a reversible thallium defect, elevating the risk by 4.3-fold. Late cardiac events occurred in 53 (15.2%) surgical survivors or nonsurgically treated patients. Patients with a fixed perfusion abnormality had a 24% late event rate, compared with 4.9% in those with a normal dipyridamole thallium study (p < 0.01). Cox analysis demonstrated that a fixed thallium defect was the strongest factor for predicting a late event and increased the relative risk by almost fivefold. A history of congestive heart failure was the only significant variable that contributed additional value to that of a fixed defect alone. Life-table analysis confirmed the strong relation of a fixed defect to cardiac event free survival (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Graduated compression stockings and intermittent pneumatic compression boots reduce the incidence of deep vein thrombosis. Recent studies suggest that the simultaneous use of these devices may have a synergistic prophylactic effect; however, conflicting reports also exist. Using duplex imaging, we analyzed the effect on peak venous velocity in the superficial femoral vein produced by the individual and simultaneous use of graduated compression stockings and intermittent pneumatic compression boots. Normal volunteers and postoperative patients were examined. The use of intermittent pneumatic compression boots significantly increased the peak venous velocity relative to rest, whereas the use of graduated compression stockings did not alter the peak venous velocity. Also, the addition of graduated compression stockings to legs already being treated with intermittent pneumatic compression boots did not produce a further augmentation of peak venous velocity. This study demonstrates that the simultaneous use of graduated compression stockings and intermittent pneumatic compression boots does not produce a synergistic augmentation of peak venous velocity in the superficial femoral vein.

The purpose of this study was to evaluate the ability of dipyridamole-thallium scintigraphy to predict perioperative and late cardiac events after peripheral vascular operations. A total of 262 patients had dipyridamole-thallium scintigraphy before 87 infrainguinal reconstructions, 108 abdominal aortic aneurysm operations, and 67 aortobifemoral bypass grafts that were placed for occlusive disease. Follow-up extended to 5 years (mean, 31.1 months). Logistic regression analysis selected dipyridamole-thallium scintigraphy redistribution as the best predictor of perioperative events. Fixed defects were not predictive. A Cox proportional hazards model for a variety of clinical risk factors and scan parameters identified fixed defects and a history of congestive heart failure as the strongest predictors of late cardiac events. The presence of greater than 1 or 2 fixed segments were the best predictors in patients with an abnormal scan; redistribution did not predict late events. The risk of combined perioperative or late cardiac events was 29% for infrainguinal, 19% for abdominal aortic aneurysm, and 7.5% for aortobifemoral operations. Life-table analysis showed that after a cluster of perioperative events that occurred primarily in patients with dipyridamole-thallium scintigraphy redistribution, most of the late cardiac morbidity and deaths occurred in patients with fixed defects.

This prospective randomized study of 50 patients compares the prevalence of complications between surgical and percutaneous methods of removal of intraaortic balloons. All patients who had percutaneous placement of a 9.5F intraaortic balloon during a 6-month period were eligible for the study. Patients were excluded if the intraaortic balloon was placed surgically, if a coagulopathy was present, or if acute leg ischemia developed at any time after insertion. After informed consent, 25 patients were randomized to each method of removal. Two complications occurred in the surgical group, including a wound infection and a lymph fistula. In one patient in the percutaneous group, a false aneurysm of the femoral artery developed. There was no significant difference between the mean of 59 minutes for percutaneous removal and 47 minutes for operative removal of the balloon (p = 0.74). The percutaneous method is therefore more cost-effective, because it does not require the use of operating room personnel or equipment necessary for surgical removal. The results of this study indicate that the majority of percutaneously placed intraaortic balloons may be safely removed percutaneously. Surgical removal of 9.5F intraaortic balloons is recommended for patients with bleeding diatheses, hemorrhagic or ischemic complications, or for those in whom the intraaortic balloon was inserted with a surgical procedure.

The purpose of this study was to quantitate the operative risk and costs encountered in the surgical treatment of institutionalized patients. Operative complications and duration of hospitalization for 200 institutionalized patients were compared with those in a control group of patients matched for age, sex, and type of operation drawn from the general hospital population. Postoperative complications occurred in 53 (26.5%) of the patients in the study group compared with 15 (7.5%) of the patients in the control group. Elective laparotomy was followed by a complication in 48% of institutionalized patients compared with 11.6% of matched controls. Emergency celiotomy carried a 75% complication rate in the study group. Atelectasis and pneumonia accounted for 50% of the postoperative complications and occurred with greatest frequency following intra-abdominal procedures. The median hospital stay for all institutionalized patients was 3 days more than for matched controls. A strategy for postoperative treatment is presented, with particular emphasis on prevention of pulmonary complications.

Transatrial placement of a Greenfield filter at the time of cardiac surgery was performed on three patients with recent femoral venous thrombosis and unstable angina, and at the time of pulmonary embolectomy on four others. The filter carrier was passed through the right atrial cannulation site under fluoroscopic guidance into the inferior vena cava. A preliminary venacavogram was performed through the carrier or a previously placed angiographic catheter. Two complications were encountered: the first was misplacement of a filter in the right renal vein before routine venacavography was employed; the second was caudal displacement of a filter by a right atrial venous drainage cannula that projected into the inferior vena cava. The latter complication can be prevented by the use of a right atrial "sump" drain that does not protrude into the inferior vena cava.

Pain or tenderness of an abdominal aortic aneurysm is widely believed to signify acute expansion and imminent rupture. To assess the potential benefit of emergency operation for the group of patients with an acutely expanding aneurysm, the clinical course of 19 patients with a symptomatic but unruptured expanding abdominal aortic aneurysm was compared with 117 patients undergoing elective abdominal aortic aneurysm resection, and 69 patients having operation for a ruptured abdominal aortic aneurysm. Postoperative morbidity was high in the patients with an expanding abdominal aortic aneurysm, and included a 21% incidence of myocardial infarction, a 10% incidence of stroke, a 37% risk of ventilatory failure, and a 31% incidence of acute renal failure, which was not statistically different from the results in patients having ruptured abdominal aortic aneurysm resection. Patients undergoing elective abdominal aortic aneurysm resection had only an 8% risk of myocardial infarction, and only a 2% risk of stroke, ventilatory failure, or renal failure. The mortality rate for expanding abdominal aortic aneurysm resection was 26% compared to 35% for ruptured abdominal aortic aneurysm (p = 0.31). Both emergency operations had a mortality rate more than five times greater than the 5.1% after elective procedures (p = 0.008). Our findings emphasize the need for early and aggressive treatment of abdominal aortic aneurysm in the elective setting, even in the patient at high risk, and suggest that the preoperative assessment and modification of risk factors is important to prevent the cardiac, cerebrovascular, pulmonary, and renal complications seen accompanying an emergency operation of this magnitude.

Controversy exists as to whether patients suspected of having deep vein thrombosis (DVT) can be studied safely without venography, with its attendant expense, inconvenience, and potential risk. We used impedance plethysmography (IPG) in 1,464 consecutive patients suspected of having DVT, with 96% of these patients with normal IPGs, there were no fatal pulmonary emboli (PE). The incidence of nonfatal PE was 1%. In 284 outpatients suspected of having DVT, but discharged without treatment because of normal IPGs, only one patient returned with subsequent symptoms of DVT (0.4%). Noninvasive testing with IPG is a safe and highly cost-effective alternative to venography for routine management of patients suspected of DVT.

Brachial plexus injury may be a consequence of median sternotomy. In a previous study, we documented that median sternotomy can cause first rib fractures and that the first rib fractures may be associated with brachial plexus injury. In the current study, two groups of patients were compared for the incidence of brachial plexus injury and first rib fracture. In Group A, an Ankeney retractor was used with the crossbar placed caudal to the incision: in Group C, a Cooley sternal retractor was used with the crossbar placed cephalad to the incision. The major effective difference between these two retractors was the more caudal placement of the retractor blades with the Cooley retractor than with the Ankeney retractor. Our previous study showed that first rib fractures were caused by high placement of the sternal retractor and that they could be avoided by placing the retractor at a lower position. In the present study, 33% in Group A and 14% in Group C sustained first rib fractures (p = 0.024). Signs of brachial plexus injury occurred in 18% of Group A and 12% of Group C (p = 0.52). We found no correlation between the presence of rib fracture and the presence of neurologic symptoms, but all patients who had both neurologic symptoms and a rib fracture had the symptoms only on the same side as the rib fracture. We also found that standard chest x-ray films identified only 15% of the rib fractures seen on special first rib views. The study demonstrates that the incidence of first rib fractures following median sternotomy is reduced when the sternal retractor is placed at a lower position and that the incidence of brachial plexus injury may also thereby be reduced.

Two groups of elective coronary artery bypass graft (CABG) patients were compared with respect to a single variable: method of cardioplegia administration. All patients had saphenous vein grafts and all distal anastomoses were done with continuous aortic occlusion and intermittent administration of a 4 degrees C cardioplegic solution. One hundred patients in Group I had the distal anastomoses performed before the proximal anastomoses with cardioplegic solution administered only via the aortic root. One hundred patients in Group II had the proximal anastomoses performed first so that cardioplegic solution also perfused beyond coronary obstructions as each subsequent distal anastomosis was completed. Aortic occlusion averaged 6 minutes longer in Group II (46.5 minutes) than in Group I (40.3 minutes) (p less than 0.01). Mortality from cardiac causes was six times greater in Group I than in Group II (6% versus 1% p = 0.027) and overall mortality was eight times greater in Group I than in Group II (8% versus 1%; p = 0.008). We conclude that earlier cardioplegic perfusion of myocardium beyond obstructed coronary arteries substantially improves myocardial protection.

Venous occlusion impedance plethysmography (IPG) is an objective noninvasive test which is widely employed for the detection of deep venous thrombosis (DVT) in the lower extremities. The IPG technique is easily adapted to the evaluation of upper extremity venous thrombosis, as demonstrated in 46 patients with symptoms of axillary and subclavian venous thrombosis (88 limbs) and 26 normal volunteers (52 limbs). Venograms were obtained in 18 patients (22 limbs) and correlated in all cases with the previous IPG interpretation. The test procedure and interpretation criteria for the noninvasive detection of upper extremity deep venous thrombosis are similar to those previously developed for the lower extremities, but with more emphasis on comparison with the contralateral limb. Vascular laboratories performing IPG for lower extremity DVT should be able to employ this test for the detection of upper extremity venous thrombosis as well.

In order to determine the best method for removal of the percutaneous intra-aortic balloon (IAB), we divided 38 patients into two groups. The IAB was removed percutaneously in Group I and surgically in Group II. There were two hemorrhagic and four thrombotic complications sufficiently severe to necessitate vascular surgical intervention in Group I. There were no vascular complications in Group II (p less than 0.1). Among the 19 patients in Group II, eight were found to have acute thrombosis of the superficial or deep femoral artery at the time of operation. It is concluded that thrombus development at the site of IAB insertion is a common event and often leads to acute ischemia. Surgical removal of a percutaneously placed IAB is recommended because it provides an opportunity for the detection and removal of thrombotic material, as well as careful closure of the puncture site.

Electrocardiographically monitored arterial stress testing was performed before surgery in 130 patients with peripheral vascular disease. When limitations of claudication or pain at rest precluded treadmill exercise, arm ergometry was employed. The electrocardiographically monitored arterial stress test proved a cost-effective, easily applicable means of screening for coronary artery disease in this group of patients. Unlike statistical analyses of historical risk factors, the electrocardiographically monitored arterial stress test evaluates the current functional state of the myocardium. We believe that preoperative electrocardiographic exercise testing should be employed more widely and should be considered in any patient facing major surgery in whom coronary artery disease is suspected on the basis of past history or known risk factors. In patients who have an ischemic response to exercise, particularly at less than 75 percent of the maximum predicted heart rate, coronary angiography and possibly coronary revascularization should be considered before elective major surgery is performed.

To document both the long-term survival and the quality of life of patients following surgery for ruptured abdominal aortic aneurysm (AAA), the records of 65 patients with ruptured AAA resection were compared with those of 100 who underwent elective AAA resection. The actuarial survival following ruptured aneurysm surgery was 92%, 51%, and 51% at 1, 5, and 10 years, respectively, and did not differ statistically for patients after elective AAA surgery or for an age- and sex-matched sample from the general population. Based on responses to a quality of life survey, there were no discernible differences in life-style, degree of independence, or productivity following either ruptured or elective AAA surgery. Survivors of ruptured AAA have an excellent long-term prognosis and expectation for a good quality of life.

Polytetrafluoroethylene (PTFE, Gortex) grafts have several advantages over woven Dacron grafts for the insertion of intra-aortic balloons (IABP). Because of the smooth inner surface of the PTFE graft, an 8-mm graft may be used instead of the 10-mm minimum size with Dacron. The pliability of the PTFE graft makes it easier to sew with fine suture material, and its comformability permits a "blood tight" seal to be obtained with a single Dacron umbilical tape tie. We have used PTFE grafts for IABP insertion in 24 patients, with no infectious or thrombotic complications. This graft material seems to offer substantial technical advantages over woven Dacron for the insertion of IABP and subsequent arterial repair.

In patient with no conventional radiographic signs of thoracic aortic rupture, an unusual physical finding, femoral embolus with ischemia, led to the correct diagnosis.

Transvenous interruption of the inferior vena cava was successful in 45 of 47 consecutive patients treated during a 41/2-year period. Greenfield filters were used in 40, and Mobin-Uddin umbrellas in 5 others. Technical details of the insertion procedure are of particular importance for successful implantation of the Greenfield device. Follow-up data were available for 34 of 36 surviving patients and autopsy findings for 4 of the 11 who had died. Patency of the vena cava was assessed by radionuclide scan, venography, or autopsy. Of 33 patients with Greenfield filters who were evaluated, only one had an occluded filter, for a patency rate of 97%. One of the three patients with a Mobin-Uddin umbrella had caval thrombosis. Severe postoperative venous stasis was seen in one patient with a Greenfield filter and one with a Mobin-Uddin umbrella. Significant distal migration or angulation of Greenfield filters was observed in six patients and is a theoretical cause for recurrent embolization. The 30-day mortality rate for the patients who had transvenous procedures was 13%, but no deaths were attributed to the procedure itself. There were no clinically evident pulmonary emboli during the follow-up period. In the present study we have documented low operative morbidity and mortality rates as well as complete protection from recurrent pulmonary embolism using transvenous interruption of the inferior vena cava. Although the Greenfield filter is somewhat bulkier and more difficult to insert than the Mobin-Uddin umbrella, it has a clear advantage because of its superior long-term patency.