Faculty Bibliography

OBJECTIVE: The standard technique of balloon angioplasty with or without subintimal dissection of infrainguinal arteries requires contrast arteriography and fluoroscopy. We attempted to perform this procedure with duplex guidance to avoid the use of nephrotoxic contrast material and eliminate or minimize radiation exposure. METHODS: From September 2003 to June 2005, 196 patients (57% male) with a mean age of 73 +/- 10 years (range, 42-97 years) had a total of 253 attempted balloon angioplasties of the superficial femoral and/or popliteal artery under duplex guidance in 218 limbs. Critical ischemia was the indication in 38% of cases, and disabling claudication was the indication in 62%. Hypertension, diabetes, chronic renal insufficiency, smoking, and coronary artery disease were present in 78%, 51%, 41%, 39%, and 37% of patients, respectively. The TransAtlantic Inter-Society Consensus (TASC) classification was used for morphologic description of femoral-popliteal lesions. The common femoral artery was cannulated under direct duplex visualization. Still under duplex guidance, a guidewire was directed into the proximal superficial femoral artery, across the diseased segment(s), and parked at the tibioperoneal trunk. The diseased segment(s) were then balloon-dilated. Balloon diameter and length were chosen according to arterial measurements obtained by duplex scan. Hemodynamically significant defects causing diameter reductions greater than 30% and peak systolic velocity ratios greater than 2 were stented with a variety of self-expandable stents under duplex guidance. Completion duplex examinations and ankle-brachial indices were obtained routinely before hospital discharge. RESULTS: There were 11 (4%) TASC class A lesions, 31 (12%) TASC class B lesions, 177 (70%) TASC class C lesions, and 34 (14%) TASC class D lesions in this series. The overall technical success was 93% (236/253 cases). Eight of the 17 failed subintimal dissections belonged to TASC class C and the remaining 9 to TASC class D. End-stage renal disease was the only significant predictor of subintimal dissection failure in patients with femoral-popliteal occlusions (5/17 cases; P < .04). Intraluminal stents were placed in 153 (65%) of 236 successful cases. Overall pre-procedure and post-procedure ankle-brachial indices changed from a mean of 0.69 +/- 0.16 (range, 0.2-1.1) to 0.95 +/- 0.14 (range, 0.55-1.3), respectively (P < .0001). The mean duration of follow-up was 10 +/- 7 months (range, 1-29 months). The overall 30-day survival rate was 100%. Overall limb salvage rates were 94% and 90% at 6 and 12 months, respectively. Six-month patency rates for TASC class A, B, C, and D lesions were 89%, 73%, 72%, and 63%, respectively. Twelve-month patency rates for TASC class A, B, C, and D lesions were 89%, 58%, 51%, and 45%, respectively. CONCLUSIONS: Duplex-guided balloon angioplasty and stent placement seems to be a safe and effective technique for the treatment of infrainguinal arterial occlusive disease. Technical advantages include direct visualization of the puncture site, accurate selection of the proper size balloon and stent, and confirmation of the adequacy of the technique by hemodynamic and imaging parameters. Additional benefits are avoidance of radiation exposure and contrast material.

Owing to the overall poor medical health of patients with end-stage renal disease, we have sought alternatives to the use of general anesthesia for access procedures. Furthermore, since local anesthesia (1) does not offer the motor block that is sometimes desired and (2) can be difficult to maintain when a large amount of vein needs to be transposed, we examined whether regional blocks can be useful for the creation of new arteriovenous fistulae (AVF). From August 2002 to January 2005, 41 patients scheduled for AVF placement underwent a regional block with the use of a lidocaine and ropivacaine mixture using a nerve stimulator. Either axillary, interscalene, or infraclavicular blocks or a combination was used. Intraoperative duplex ultrasonography was used to assess the degree of venodilatation of the basilic and cephalic veins before and after the block. The site of each measurement was marked on the skin and selected by a clearly identifiable branch point. Each measurement was recorded three times and was made in the (1) native state, (2) after application of a tourniquet with opening and closing of the hand for 15 seconds, and (3) after placement of the block. The average age of the patients was 65 +/- 14 years (SD), with ages ranging from 33 to 91 years, and the prevalence of diabetes mellitus was 50%. Complete brachial plexus block was achieved in 34 patients (83%). Sensory block was accomplished within 10 to 15 minutes and usually lasted 4 to 6 hours. Motor block was accomplished in 10 to 25 minutes. Venodilatation was not noted in patients whose blocks did not work (n = 7) or whose vein was found to be phlebitic on exploration (n = 3). The degree of venodilatation noted as a percentage increase after application of the tourniquet compared with the native state for these 34 patients (in whom the block worked) was 37% for the distal cephalic, 31% for the midcephalic, and 32% for the midbasilic vein. The degree of venodilatation noted as a percentage increase after placement of the block compared with after tourniquet application for these 34 patients was 42% for the distal cephalic, 19% for the midcephalic, and 26% for the midbasilic vein. No instances of systemic toxicity, hematomas, or nerve injury from the block were noted. Accesses placed included 20 radiocephalic AVF, 8 brachiobasilic AVF, 8 brachiocephalic AVF, 2 arteriovenous grafts, 2 radiobasilic AVF, and 1 brachial vein AVF.Regional block is a safe and, in our opinion, preferred technique for providing anesthesia for upper extremity vascular surgery. The venodilatation observed is augmented compared with that using a tourniquet and may allow more options for access placements.

We have noted a significant incidence of pulmonary embolism (PE) and mortality associated with upper extremity deep venous thrombosis (UEDVT). Since there is an association between site of lower extremity DVT (LEDVT) and PE, we hypothesized that there might also be a correlation between site of UEDVT and PE with associated mortality. To further elucidate this hypotheses, we analyzed the mortality and incidence of PE diagnosed with subclavian/axillary/internal jugular vein thrombosis during an 11-year period at our institution and compared the data to those of patients diagnosed with brachial DVT. We studied 598 patients diagnosed with acute internal jugular, subclavian, axillary, or brachial DVT by duplex scanning. The patients were divided into three groups based on the most proximal location of the thrombus: group I, UEDVT involving the subclavian or axillary veins (n = 467); group II, isolated internal jugular DVT (n = 80); group III, brachial DVT alone (n = 52). Mortality rates at 2 months were 29%, 25%, and 21% for each group, respectively. The number of patients diagnosed with PE by ventilation/perfusion scans in groups I, II, and III, respectively, were 5%, 6.25% and 11.5% (p = 0.13). Furthermore, stratification by risk factors failed to demonstrate factors associated with increased 2-month mortality. Contrary to the initial hypothesis of a relationship between the site of thrombosis and the incidence of PE and mortality, these data demonstrated no statistical differences in mortality or incidence of PE among the groups studied. Additionally, these data suggest that brachial vein thrombosis is a disease process related to comparable associated mortality and morbidity similar to other forms of UEDVT. Based on these data, we suggest that UEDVT may be thought of as a marker for the severity of systemic illness of the patient rather than just as a cause of venous thromboembolism.

The objective of this study was to investigate the role of inflammation, programmed cell death, its molecular modulators, and proteolysis in the pathogenesis of iliac artery aneurysms (IAAs). Nineteen IAA specimens were obtained from patients undergoing elective surgical repair. All were males with ages ranging from 55 to 85 years (mean 73 years). Controls were iliac arteries (n=6) retrieved from surgical patients without aneurysmal disease. Standard histochemical techniques were used to assess elastic lamellae fragmentation and inflammatory infiltrate in aneurysmal and normal tissues Identification of different types of cells in the aneurysm wall and detection of death-pro molecules, Fas, p53, perforin, apoptosis-mediating bcl-2 family proteins, apoptotic death substrate, and poly(adenosine diphosphate-ribose) polymerase were performed immunohistochemically. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick end-labeling (TUNEL) assay and caspase activity. Proteolytic activity was determined by 10% gelatin gel zymography. There is a conspicuous disruption and fragmentation of elastic lamellae in IAAs compared with normal arteries. Increased gelatinolytic activity was observed at 92, 72, and 67 kDa in the aneurysmal tissues. There was a significant loss of vascular smooth muscle cells (VSMCs) in the IAA walls compared with normal arteries (p < .02). Large numbers of inflammatory cells were observed in the IAA specimens (p = .01). Only aneurysmal arteries showed CD8+ T cells expressing death-promoting molecules. CD3+, CD8+, CD20+, CD30+, and CD68+ immunoreactive cells were significantly more prominent in the aneurysmal tissues than in the control arteries. There was a significant increase in the number of cells undergoing apoptosis in aneurysmal tissue than in the normal vessels (p < .02), as well as in the expression of bax, p53, CPP-32, and Fas. Apoptotic cells and proapoptotic molecules predominantly localized to the inflammatory infiltrate. VSMC apoptosis was significant in IAAs. The data confirm the architectural disruption of the IAA wall and illustrate an apparent biologic response involving inflammatory infiltrate, apoptosis, and signaling molecules capable of initiating cell death. In addition to compromising the mechanical integrity of the vessel wall, VSMC loss may contribute to imbalance in the protein profile, accelerating extracellular matrix degradation that could favor IAA development.

Although ultrasonography (US) advantageously portrays lumen and wall thickness, velocity criteria have been used primarily to interpret carotid artery stenosis. The relationship of US and velocity measurements was investigated. Peak-systolic and end-diastolic velocities (PSV, EDV) increase exponentially as the lumen of the internal carotid artery narrows and the percent stenosis (%S) increases. We tested the consistency of the, relationship between carotid velocities and US %S in two distinct data sets. One data set was used to obtain regression equations relating velocity parameters and %S based on US. Validation of these equations was conducted using a separate, independent data set. US measurements were classified in 12 %S intervals, PSV, EDV, the ratio of the internal carotid artery to the common carotid artery PSV, and %S were entered consecutively until 10 records for each %S interval were obtained. Regression equations obtained in the first data set were used to predict %S in the second data set. Predicted %S was then compared with actual US %S. The highest correlation in the first data set (r = .89) was between %S and the natural logarithm (In) of PSV. This In PSV -%S equation was then applied to a second data set of an additional 120 carotid duplex images. In the second data set, actual %S and PSV-predicted %S differed by >10% in 38 cases (32%). When all velocity-%S regression equations were used for comparison, differences between actual and at least one velocity-predicted %S were >10% in 19% of the arteries. Conversely, actual %S matched at least one prediction of %S based on velocity data in 81% of the cases. US %S differed significantly from single velocity-based estimates of %S in at least one-third of the cases. On the other hand, four of five US measurements were confirmed by at least one velocity parameter. Emphasis on US, in addition to velocity data, is recommended for the interpretation of duplex US carotid examinations.

INTRODUCTION: Transforming growth factor-beta 1 (TGF-beta 1 ) is known to maintain a balance between apoptosis and cellular dysfunction and therefore may have a pivotal role in vessel remodeling during pathogenesis of vascular disorders. We previously demonstrated that inducible nitric oxide synthase (iNOS) mediates signal transduction in vascular wall during the development of varicose veins. Currently, we investigated the expression and correlation of TGF-beta 1 , iNOS, monocyte/macrophage infiltration, and loss of vascular smooth muscle cells (VSMCs), in a series of normal and varicose vein specimens. METHODS: Twenty varicose vein specimens were retrieved from 20 patients undergoing lower-extremity varicose vein excision, and 27 normal greater saphenous vein segments (controls) were obtained from 27 patients undergoing infrainguinal arterial bypass surgery. Principal risk factors (diabetes mellitus, hypertension, tobacco abuse) were also compared. Varicose vein segments were separated into tortuous and nontortuous regions based on their macroscopic and microscopic morphology. VSMC actin, CD68 + monocytes/macrophages, iNOS, and TGF-beta 1 , were examined by immunohistochemistry, immunoblotting, and real-time reverse transcriptase polymerase chain reaction. RESULTS: According to the CEAP classification for chronic lower extremity venous disease, most of the patients were in class 2 for clinical signs of the disease (n = 11). Mean ages were 53.6 +/- 4.7 years for the varicose vein group and 56.5 +/- 4.4 years for the controls. The gender distribution was same in both groups. Immunoreactivity to TGF-beta 1 and iNOS was significantly different in the tortuous regions of the varicose veins compared with nontortuous regions (P < .01). Not only was a significantly higher expression of iNOS noted in the varicose vein group (P < .001), but a differential expression of iNOS was also observed in the tortuous and nontortuous portions of the varicose veins. Significant overexpression of TGF-beta 1 (P < .01) that correlated with overproduction of iNOS and with increased presence of CD68 + monocytes/macrophages was observed in the varicose vein walls compared with normal veins. CONCLUSIONS: This is the first evidence of TGF-beta 1 , as well as iNOS, being differentially upregulated in nontortuous and tortuous segments of varicose veins. The increased expression of TGF-beta 1 and presence of macrophages, correlating with overproduction of iNOS, may be associated with varicosity development and deserves further study. CLINICAL RELEVANCE: The pathogenesis of varicose veins, the most common manifestation of chronic venous disease, is debatable. Elucidation of mechanisms involved in the disease process is the first step to improved therapeutic modulations. Towards this goal, the relationship between NO production and TGF-beta 1 in the molecular pathophysiology of chronic venous disease was investigated. The data identify for the first time, an important role for TGF-b1-iNOS-monocyte/macrophage signaling in the etiology of varicosities. Furthermore, we determine if there are any significant differences within the varicose vein group itself based on regional differences, by classifying the varicose tissues into tortuous and non-tortuous segments.

OBJECTIVE: To elucidate the natural history of upper extremity deep venous thrombosis (UEDVT), we examined factors that may contribute to the high mortality associated with UEDVT. METHODS: Five hundred forty-six patients were diagnosed with acute internal jugular/subclavian/axillary deep venous thrombosis from January 1992 to June 2003 by duplex scanning at our institution. There were 329 women (60%). The mean age +/- SD was 68 +/- 17 years (range, 1-101 years). Risk factors for UEDVT were the presence of a central venous catheter or pacemaker in 327 patients (60%) and a history of malignancy in 119 patients (22%). Risk factors for mortality within 2 months of the diagnosis of UEDVT that were analyzed included age, sex, presence of a central venous catheter or pacemaker, history of malignancy, location of UEDVT, concomitant lower extremity deep venous thrombosis, systemic anticoagulation, placement of a superior vena caval filter, and pulmonary embolism. RESULTS: The overall mortality rate at 2 months was 29.6%. The number of patients diagnosed with pulmonary embolism by positive ventilation/perfusion scan or computed tomographic scan was 26 (5%). The presence of a central venous catheter or pacemaker ( P < .001), concomitant lower extremity deep venous thrombosis ( P = .04), not undergoing systemic anticoagulation ( P = .002), and the placement of a superior vena caval filter ( P = .02) were associated with mortality within 2 months of the diagnosis of UEDVT by univariate analysis. Pulmonary embolism ( P = .42), sex ( P = .65), and a history of malignancy ( P = .96) were not. CONCLUSIONS: These data suggest that the high associated mortality of UEDVT may be due to the underlying characteristics of the patients' disease process and may not be a direct consequence of the UEDVT itself.

The traditional approach for patent and exposed and infected infrainguinal bypass grafts in the groin has included wide operative debridement and secondary or delayed primary closure. However, this has been associated with significant risk of further contamination and length of stay. The authors reviewed their experience using the wide debridement, sartorius muscle flap transposition, and primary wound closure as an alternative. During the past 5 years, they have had 50 patients with major wound necrosis or infection in the groin or thigh with the graft or native artery being exposed after debridement. This group included 28 men; 74% of the patients had hypertension, 58% had diabetes, and 20% had renal failure. The grafts were split evenly between native vein and prosthetic material. After wide debridement, closure was performed by the vascular surgeon using the sartorius muscle flap. Postoperatively, there was an 8% major amputation rate and a 12% mortality rate in the first 30 days. One patient developed a pseudoaneurysm 5 weeks after placement of the flap. This patient underwent removal of the infected polytetrafluoroethylene graft with ligation of the common femoral artery. None of the procedures have resulted in further systemic or graft sepsis. None have resulted in arterial or graft blowout. Follow-up was for an average of 18 months. Closure of groin and thigh wounds with exposed bypass graft or native artery can be safely performed with the sartorius muscle flap with excellent results. The length of stay of these patients compared to historical controls is acceptable. Furthermore, the chance of infection of the native artery or bypass may be reduced. Familiarity with this simple technique can be a valuable tool for the vascular surgeon.

Von Hippel-Lindau (VHL) gene is a tumor suppressor gene that plays a genome "gatekeeper'' role and controls several downstream effector genes. We have previously demonstrated that both in vivo and in vitro adenovirus-mediated gene transfer of tumor suppressor genes into the vascular endothelium is effective in decreasing neointimal hyperplasia and abnormal cell proliferation. The degree of apoptosis induced by these genes is critical in mediating the in vivo responses to gene therapy and the maintenance of the crucial balance between cell death and viability. Since VHL gene is known to regulate vascular endothelial growth factor (VEGF) as well as other angiogenic factors, it may exhibit a greater potential in the attenuation of vascular disorders in comparison to other tumor suppressor genes. This study focused on whether adenovirus-mediated VHL gene transfer into human vascular smooth muscle cells has an effect on cell proliferation and induction of apoptosis. Human aortic smooth muscle cells (HASMC) were grown as monolayers and transfected with varying titers of adenovirus containing the VHL cDNA (AdVHL). The negative controls were adenovirus containing green fluorescent protein (AdGFP), vector alone (AdNull), and virus-free infection medium. Adenovirus encoding wild-type p53 (Adp53) was used as positive control. Cell viability and proliferation were determined by using trypan blue exclusion and MTS-based CellTiter 96 AQ Proliferation Assay. Apoptosis was evaluated by TUNEL assay, morphologic changes, and nucleosomal DNA degradation. Following AdVHL transfection HASMCs demonstrated a dose-dependent decrease in viability as compared to negative controls (p < 0.05). AdVHL-transfected cells exhibited a decrease in their proliferative ability by 40.21 +/-1.66 (SEM)%. In cultures transfected with the positive control, Adp53, the cell viability as well as proliferation was highly reduced (p < 0.001). AdGFP and AdNull did not increase HASMC apoptosis above baseline levels. The cells exposed to adenoviruses expressing tumor suppressor genes underwent apoptosis, with Adp53 demonstrating a very high magnitude of cell death (75.27 +/-3.52 [SEM]%). AdVHL expression caused 45.36 +/-2.55 (SEM)% apoptosis in HASMC. Recombinant adenovirus-mediated VHL expression is efficacious in limiting vascular smooth muscle cell growth in vitro. Overexpression of VHL suppresses HASMC proliferation and regulates apoptosis. Further experiments are indicated to examine whether VHL may be a useful adjunct in limiting myointimal hyperplasia.

The authors have noted a significant incidence of pulmonary embolism and mortality associated with upper extremity deep venous thrombosis (UEDVT). Since there is an association between the site of lower extremity DVT (LEDVT) and pulmonary embolism, they hypothesized that there might also be a correlation between the site of UEDVT and the incidence of pulmonary embolism (PE) and associated mortality. To further elucidate this hypothesis, they analyzed the mortality rate and incidence of PE diagnosed with subclavian/axillary or internal jugular vein thrombosis during a 5-year period at their institution. Two hundred and ten patients were diagnosed with acute internal jugular and/or subclavian/axillary DVT during a 5-year period by duplex scanning. The indications for the duplex examination were upper extremity swelling in 187 (89%) or as part of the work-up for pulmonary embolism in 23 (11%). There were 126 women (60%) and 84, men (40%). The mean age was 67 +/-18 years (range 1-101 years). The patients were divided into 3 groups based on the location of the thrombus: Group I-UEDVT involving the subclavian and/or axillary veins (n = 128); Group II-internal jugular vein thrombosis alone (n = 21); and Group III-concomitant subclavian/axillary and internal jugular vein DVT (n = 61). Risk factors were presence of central venous catheter or pacemaker in 127 patients (60%), malignancy in 78 patients (37%), concomitant lower extremity deep venous thrombosis (LEDVT) in 40 patients (19%), and history of LEDVT in 6 patients (3%). Eighty (38%) patients had more than 1 risk factor. The mean follow-up period was 13 +/-1 months (range 0-49 months). Mortality rates at 1, 3, and 12 months were 13%, 31%, and 40% for Group I; 14%, 33%, and 42% for Group II; and 23%, 44%, and 59% for Group III. The mortality rate in Group I was statistically significantly higher for patients >/=75 years old, patients not treated with anticoagulation, and patients who underwent placement of a central venous line. The same risk factors did not achieve statistical significance in the 2 other groups. The number of patients diagnosed with pulmonary embolism by ventilation/perfusion scans in Groups I, II, and III that could be attributed to the UEDVT solely was 8 (4%), 1 (0.5%), and 3 (2.4%), respectively. Contrary to the initial hypothesis of a relationship between the site of thrombosis and the incidence of pulmonary embolism and mortality, these data showed no statistical differences in mortality rate or incidence of pulmonary embolism among the 3 groups studied. These data also suggest that internal jugular vein thrombosis is a disease process associated with mortality and morbidity rates comparable to those of subclavian/axillary vein thrombosis.