Estrogen inhibits the vascular injury response in estrogen receptor alpha-deficient mice.

The atheroprotective effects of estrogen in women are well recognized, but the underlying mechanisms responsible are not well understood. Blood vessel cells express the classic estrogen receptor, ER alpha (ref. 2-6), and are directly affected by estrogen, which inhibits the development of atherosclerotic and injury-induced vascular lesions. We have generated mice in which the ER alpha gene is disrupted and have used a mouse model of carotid arterial injury to compare the effects of estrogen on wild-type and estrogen receptor-deficient mice. Increases in vascular medial area and smooth muscle cell proliferation were quantified following vascular injury in ovariectomized mice treated with vehicle or with physiologic levels of 17 beta-estradiol. Surprisingly, in both wild-type and estrogen receptor-deficient mice, 17 beta-estradiol markedly inhibited to the same degree all measures of vascular injury. These data demonstrate that estrogen inhibits vascular by a novel mechanism that is independent of the classic estrogen receptor, ER alpha.

Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release.

BACKGROUND: Moderate red wine consumption is inversely associated with coronary ischemia, and both red wine and purple grape juice (PGJ) contain flavonoids with antioxidant and antiplatelet properties believed to be protective against cardiovascular events. Acute cardiac events are also associated with decreased platelet-derived nitric oxide (NO) release. In this study, the effects of PGJ and PGJ-derived flavonoids on platelet function and platelet NO production were determined. METHODS AND RESULTS: Incubation of platelets with dilute PGJ led to inhibition of aggregation, enhanced release of platelet-derived NO, and decreased superoxide production. To confirm the in vivo relevance of these findings, 20 healthy subjects consumed 7 mL. kg(-1). d(-1) of PGJ for 14 days. Platelet aggregation was inhibited after PGJ supplementation, platelet-derived NO production increased from 3.5+/-1.2 to 6.0+/-1.5 pmol/10(8) platelets, and superoxide release decreased from 29.5+/-5.0 to 19.2+/-3.1 arbitrary units (P<0.007 and P<0.05, respectively). alpha-Tocopherol levels increased significantly after PGJ consumption (from 15.6+/-0.7 to 17.6+/-0.9 micromol/L; P<0.009), and the plasma protein-independent antioxidant activity increased by 50.0% (P<0.05). Last, incubation of platelets with select flavonoid fractions isolated from PGJ consistently attenuated superoxide levels but had variable effects on whole-blood aggregation, platelet aggregation, and NO release. CONCLUSIONS: Both in vitro incubation and oral supplementation with PGJ decrease platelet aggregation, increase platelet-derived NO release, and decrease superoxide production. These findings may be a result of antioxidant-sparing and/or direct effects of select flavonoids found in PGJ. The suppression of platelet-mediated thrombosis represents a potential mechanism for the beneficial effects of purple grape products, independent of alcohol consumption, in cardiovascular disease.

Who needs surveillance of the contralateral carotid artery?

BACKGROUND: Although the value of carotid endarterectomy has been proven, postoperative surveillance remains controversial. The purpose of this study was to determine the natural history of disease progression in the contralateral carotid artery by duplex surveillance, and to assess the cost of stroke prevention on this contralateral side. METHODS: Vascular laboratory records were reviewed to identify carotid endarterectomy patients who had two or more duplex studies between 1984 and 1995. Critical stenosis was defined as > or = 75% area reduction. RESULTS: In all, 324 patients were followed up with duplex scans for 1 month to 11 years (mean 30.3 months). The only factors that correlated with progression to critical stenosis were age and initial stenosis. Overall, 19.5% of patients progressed to critical stenosis within 5 years while the high-risk groups with age > 65 years or initial stenosis > or = 50% progressed to critical disease in 27% and 39%, respectively (P < or = 0.05). The cost per stroke prevented ranged from $143,500 to $418,200 when stratified by initial stenosis. CONCLUSION: Patients who have undergone a carotid endarterectomy demonstrate a propensity for progression of carotid stenosis in the unoperated (contralateral) artery. The cost/benefit ratio may be improved by varying the intensity of duplex surveillance of the contralateral carotid based on the patient's age and initial degree of stenosis.

Transesophageal echocardiography for hemodynamic management of thoracoabdominal aneurysm repair.

Maintenance of cardiovascular stability during thoracoabdominal aneurysm repair remains a formidable challenge. Transesophageal echocardiography (TEE) has been shown to be an excellent method for detecting myocardial ischemia and assessing left ventricular volume. We examined the utility of TEE in a group of 17 patients from an overall series of 33 patients who underwent thoracoabdominal aneurysm resection between 1988 and 1992. The mortality rate was 9%, whereas the incidences of myocardial infarction and paraplegia were 13% and 6%, respectively. Intraoperative management was significantly altered by TEE data in nine patients. Two patients were noted to have mitral valve insufficiency, and one had transient ischemia-induced regional wall abnormalities. In six patients, Swan-Ganz-derived filling data failed to identify severe hemodynamic alterations that were noted on TEE. Five patients were hypovolemic and hyperdynamic, whereas one was in florid congestive heart failure. Further investigation is warranted to prospectively validate this technique.

Primary tibial vein aneurysm: a source of pulmonary emboli.

OBJECTIVE: To describe a case of a rare type of venous aneurysm (posterior tibial) with associated pulmonary embolus. We will discuss options and considerations germane to the diagnostic evaluation and possible interventions for this challenging clinical scenario. METHODS: Case presentation and literature review. RESULTS: A 36-year-old man presented to an outside hospital with a three-day history of left calf pain, acute shortness of breath and syncope elicited by exercise. Work-up demonstrated a pulmonary embolus and a posterior tibial venous aneurysm with mural thrombus. The patient presented to us 18 months later with persistent calf pain seeking an alternative to recommendations of lifelong anticoagulation. The patient was treated with surgical resection of the venous aneurysm with subsequent discontinuation of his anticoagulation. There were no surgical or thrombotic complications of this treatment course and the patient's discomfort improved. CONCLUSION: Primary aneurysms of the tibial veins as a cause of pulmonary emboli are rare. A review of the literature suggests that anticoagulation alone does not provide effective amelioration of thromboembolic risk from lower extremity venous aneurysms. We have reported a case of successful surgical treatment of a posterior tibial venous aneurysm and recommend that surgical correction be strongly considered for accessible venous aneurysms.

The small saphenous vein and other 'neglected' veins of the popliteal fossa: a review.

The small saphenous vein (SSV) and other veins in the popliteal fossa merit little discussion in the literature or in didactic programmes regarding their role in chronic venous insufficiency (CVI) and, in this sense, they are neglected. The purpose of this review is to present both duplex ultrasound findings and the associated clinical characteristics of patients with SSV reflux, from several large series. Both the anatomic variations and the epidemiology of the SSV, as well as other veins of the popliteal fossa, the gastrocnemius veins, Gocamini vein, popliteal area veins and popliteal vein, will be discussed. Findings from our review of the current available literature will demonstrate the important role that these veins play in association with CVI. The implications for open and endovenous surgery will be underlined.

Gasless laparoscopic cholecystectomy in pregnancy.

Although laparoscopic cholecystectomy has become the surgical procedure of choice for most patients with cholecystitis, the safety of carbon dioxide (CO2) pneumoperitoneum during pregnancy has not been fully elucidated. Pregnancy causes many physiologic changes, resulting in compromised cardiac, pulmonary, and metabolic reserves. The use of CO2 pneumoperitoneum during laparoscopy may cause further physiologic stress to both the parturient and the fetus. A case of gasless laparoscopic cholecystectomy is presented. This procedure avoids potential risks of both absorbed CO2 and increased intraabdominal pressure.

Endoscopic in situ bypass. A gentler dissection.

We believe that this is the first report of a gasless endoscopic in situ bypass technique. We have pursued this minimally invasive procedure with the hope that wound complications and operative time might be improved without compromising graft patency. Having demonstrated the feasibility of minimally invasive lower-extremity bypass we would urge further study to assess the safety and efficacy of this promising approach.

Adjuvant techniques for the management of large carotid body tumors. A case report and review.

Although the first successful resection of a carotid body tumor was reported over 100 years ago this operation remains technically challenging with many potential pitfalls. The case of a man with a large (8 cm) carotid body tumor will be presented in order to identify key issues that pertain to effective diagnostic and therapeutic modalities. A multidisciplinary team (vascular surgeon, neurosurgeon, neuroradiologist, interventional radiologist and oromaxillofacial surgeon) provided specific expertise on each aspect of the patient's evaluation and treatment. Adjuvant techniques employed in this case included angiographic tumor embolization, jaw subluxation, strap muscle division, nasotracheal intubation, carotid resection and saphenous vein interposition grafting.

Growth factors in bone matrix. Isolation of multiple types by affinity chromatography on heparin-Sepharose.

The mineralized matrix of osseous tissue harbors abundant mitogenic activity which is extractable by demineralizing solvents. In bovine bone powder free of blood and cartilage contamination, the volume concentration of mitogens is up to 20 times greater than in serum. Growth factor activity in bone extracts was quantitated on quiescent mouse BALB/c/3T3 fibroblasts, where [3H]thymidine incorporation for 48 h was stimulated up to 200-fold in a linear, dose-dependent manner. Six distinct bone-derived growth factors (BDGFs) have been resolved and partially purified (up to 44,000-fold) on heparin-Sepharose using NaCl gradient elution. Provisionally named by the NaCl molarity at which they elute, these BDGFs include BDGF-0.45 (25% of total activity). This factor is heat-stable and sensitive to dithiothreitol, and displaces 125I-labelled bovine platelet-derived growth factor in a radioreceptor assay. BDGF-0.45 (approximately 50 ng/g of bone) is closely related or identical to bovine platelet-derived growth factor. BDGF-1.1 (10%) has a pI of 5.2 and shows a 16,600-dalton doublet on sodium dodecyl sulfate-polyacrylamide gel electrophoresis Western blots stained with antiserum to bovine anionic fibroblast growth factor. Two activities with high heparin affinity resemble cationic forms of fibroblast growth factor. BDGF-1.5 is the dominant factor in fetal membranous bone (50%), but is less abundant in adult bone (20%). BDGF-1.7, a 17,500-18,400-dalton triplet, is virtually absent in fetal bone (7%) but abundant (30%) in adult bone and may be related to cartilage derived growth factor. Two minor activities, BDGF-0.1 (10%) and BDGF-2.0 (7%) have not been characterized. Proliferation of bovine capillary endothelial cells was strongly supported by BDGFs 1.1, 1.5, and 1.7, but not by 0.45. These four purified BDGFs and the crude bone extract were also strongly mitogenic for rat osteoblasts while depressing alkaline phosphatase specific activity by 2-3-fold. Bone exhibits the most complex spectrum of growth factor activities of any tissue yet described. Bone cells and other indigenous cell types must be considered as possible sources of the BDGFs, in addition to sequestration from blood. Mechanisms for unmasking or release of BDGFs from the mineralized matrix resulting in local action on target cells are undoubtedly important for the development and maintenance of bone tissue.

Subfascial endoscopic perforator ligation: an analysis of early clinical outcomes and cost.

PURPOSE: Early results of subfascial endoscopic perforator surgery (SEPS) were examined. Data on ulcer healing, complications, and costs are presented. METHODS: Data were prospectively collected for all patients who underwent SEPS at our institution. A concurrent control group was not available because primary open perforator ligation is no longer performed at our hospital. Preoperative assessment included duplex scanning (valve closure times and perforator mapping), plethysmography, and phlebography. Completeness of therapy was assessed with postoperative duplex mapping of perforating veins. Clinical status was monitored after surgery, and actual costs, including equipment, personnel, and facilities management, are reported. RESULTS: Eighteen procedures were performed in 15 patients (mean age, 52 years; range, 42 to 65 years). Two patients underwent bilateral SEPS, and one patient underwent a second procedure on the same leg. Active ulceration (class 6) was present in 14 of 18 limbs (78%), recently healed ulcers (class 5) in two of 18 (11%), and lipodermatosclerosis with edema (class 4) in two. Deep venous insufficiency was present in 14 of 18 (78%). The number of perforating veins ligated per leg ranged from 0 to 12 (mean, 4.3). Follow-up ranged from 3 to 64 weeks (mean, 22 weeks). Complete ulcer healing occurred in eight of 14 limbs (57%) at a mean of 14 weeks. Reduction in ulcer size was noted in four of 14 (29%), and two limbs were not improved. There were no new ulcers. Residual perforating veins were noted in four of 18 limbs. None of the limbs with residual perforating veins had complete healing of ulceration. Operating room costs were higher than those associated with limited-incision open perforator ligation ($2570 vs $1883). CONCLUSION: These preliminary data suggest that when used as part of a treatment plan to correct deep and superficial venous insufficiency SEPS results in a high rate of wound healing, with no recurrent ulceration in this series. Increased operating room costs associated with longer operations and greater disposable expenses will likely be overcome by shortened length of stay and diminished wound complications. These findings emphasize the importance of ligating all incompetent perforating veins, as ulcer healing was never achieved when residual perforating veins were found at follow-up.

Clinical results of common strategies used to revise infrainguinal vein grafts.

PURPOSE: Patients who have failing infrainguinal bypass grafts or failed grafts reopened with lytic therapy represent a group at high risk of subsequent failure. Previous studies suggest that vein patch angioplasty and jump grafting may be less durable than interposition grafting as a method of correcting graft lesions. Our objective was to assess the value of various technical strategies for graft revision in a series of autogenous infrainguinal bypass grafts and to assess how these variables might affect cumulative graft patency (CGP) rates. METHODS: We retrospectively reviewed the clinical course, anatomic sites of revision, and type of revision performed on 67 grafts in 58 patients who underwent at least one revision from 1991 to 1995. Results were assessed with regression analysis and Kaplan-Meier estimates of CGP rates (p < 0.05 was considered significant). RESULTS: Sixty-seven vein grafts underwent revision of 112 anatomical sites in 95 operations. Forty-nine of 67 grafts were single-segment greater saphenous vein grafts and 18 were composite (> 1 segment) grafts, with an overall 5-year CGP rate of 72%. No difference was observed between the 4-year CGP rate in grafts with hemodynamically significant distal anastomotic stenoses repaired primarily with jump grafts (n = 20, 71% CGP rate) and those with stenoses found only in the graft body (n = 41, 89% CGP rate). Vein patch angioplasty was used primarily, but not exclusively, for focal graft body stenoses (n = 35), whereas interposition grafts (n = 11) were reserved for more diffuse strictures; no significant difference in 3-year CGP rates was observed (94% and 73%, respectively). CONCLUSION: Using an appropriate revision strategy that favors vein patch angioplasty for graft body lesions and jump grafts for distal anastomotic lesions, acceptable assisted patency rates can be achieved in grafts that are at risk for repeated failure.

Correlation of venous noninvasive tests with the Society for Vascular Surgery/International Society for Cardiovascular Surgery clinical classification of chronic venous insufficiency.

PURPOSE: Noninvasive tests for the evaluation of chronic venous insufficiency (CVI) include quantitative photoplethysmography (QPG), air plethysmography, and duplex ultrasonography measurement of valve closure time (VCT). These tests have been shown to accurately identify the presence of CVI, define the disease, and locate the involved segments. However, the correlation of noninvasive assessment of CVI with the clinical severity (Society for Vascular Surgery/International Society for Cardiovascular Surgery staging) has not been addressed critically. METHOD: During an 18-month period, 74 limbs were prospectively evaluated with clinical examination, air plethysmography, QPG and duplex ultrasonography. RESULTS: We studied 52 patients with a mean age of 46 years. There were 14 stage 0 limbs, 14 stage 1, 15 stage 2, and 31 stage 3. We found significant differences (p < 0.05) between normal limbs and those with CVI only by VCT and QPG. There were also marked trends toward worsening mean values for reflux (VCT, QPG, and venous filling index) and venous hypertension (residual volume fraction) between stages 0 to 1, and 1 to 2; however, there was a large degree of overlap between all groups. No test discriminated stage 2 from 3. Assessment of calf muscle pump function with ejection fraction showed no difference between any groups. CONCLUSION: The Society for Vascular Surgery/International Society for Cardiovascular Surgery criteria for CVI staging distinguishes ulcerated limbs (stage 3) from those with nonulcerating skin changes (hyperpigmentation, brawny edema, and subcutaneous fibrosis) (stage 2). However, we were not able to distinguish these groups by available noninvasive methods. This may imply that these tests are not accurate enough or that the progression from lipodermatosclerosis to frank ulceration is not accounted for by large-vessel hemodynamic changes, but rather by microcirculatory alterations.

Duplex assessment of venous reflux and chronic venous insufficiency: the significance of deep venous reflux.

PURPOSE: This study was undertaken to examine the role of superficial and deep venous reflux, as defined by duplex-derived valve closure times (VCTs), in the pathogenesis of chronic venous insufficiency. METHODS: Between January 1992 and November 1995, 320 patients and 500 legs were evaluated with clinical examinations and duplex scans for potential venous reflux. VCTs were obtained with the cuff deflation technique with the patient in the upright position. Imaging was performed at the saphenofemoral junction, the middle segment of the greater saphenous vein, the lesser saphenous vein, the superficial femoral vein, the profunda femoris vein, and the popliteal vein. Not all patients had all segments examined because tests early in the series did not examine the profunda femoris or lesser saphenous vein and because some patients had previous ligation and stripping or venous thrombosis. VCTs were examined for individual segment reflux, grouped into superficial and deep systems, and then correlated with the clinical stage as defined by the SVS/ISCVS original reporting standards in venous disease. Segment reflux was considered present if the VCT was greater than 0.5 seconds, and system reflux was considered present if the sum of the segments was greater than 1.5 seconds. Between-group differences were analyzed with analysis of variance and post hoc tests where appropriate. RESULTS: Sixty-nine limbs studied were in class 0, 149 limbs were in class 1, 168 limbs were in class 2, and 114 limbs were in class 3. VCTs in the superficial veins were significantly lower in class 0 than in the other clinical classes. There was no difference in superficial reflux in the symptomatic limbs (classes 1 to 3). Reflux VCTs in the superficial femoral and popliteal veins increased as the clinical symptoms progressed, with a significant increase in class 3 ulcerated limbs when compared with nonuclerated limbs. The incidence of deep venous reflux was 60% in class 3 limbs, compared with 29% in class 2 limbs, whereas the incidence of superficial venous reflux did not differ among the symptomatic limbs. Isolated superficial femoral and popliteal vein reflux was uncommon, even in class 3 limbs, but combined superficial femoral and popliteal vein reflux was found in 53% of class 3 limbs, compared with 18.5% of class 2 limbs. CONCLUSIONS: Reflux in the deep venous system plays a significant role in the progression of chronic venous insufficiency. Deep system reflux increases as clinical changes become more severe, with significant axial reflux contributing to ulcer formation.

Reduction of hospital resources utilization in vascular surgery: a four-year experience.

PURPOSE: Managed care whether through risk or through capitated contracts results in reduction in resources, reduced length of hospital stay, and reduced utilization of hospital resources (collectively referred to as resource reductions). These resource reductions will become even more noticeable as a greater proportion of Medicare patients who need vascular operations select a managed-care senior product. We examined the results of a 4-year experience with resource management in an academic vascular surgery practice during which best practice plans were developed and implemented. METHODS: We analyzed hospital cost data, which included both total hospital and intensive care unit length of stay, average units per operation for laboratory, pharmacy, and radiology services and operating room and direct hospital costs for 257 carotid endarterectomies performed over fiscal years (FY) 1994, 1995, 1996, and 1997 (6 month data) and 175 infrainguinal bypass procedures performed during the same period. RESULTS: For carotid endarterectomy, length of stay decreased 66% over the 4-year period to an average of 2.07 days in FY97. Both radiology and pharmacy utilization were reduced after the first year of institution of best practice plans (56% and 32% respectively) with 4-year total reductions of 86% and 55% by FY97. The most notable changes included elimination of routine postoperative laboratory testing, use of aspirin rather than low-molecular-weight dextran, emphasis on oral rather than intravenous vasoactive drugs, and routine use of duplex scanning alone rather than angiography for diagnosis after FY94-95. The length of operating room time for carotid endarterectomy remained relatively constant from FY94 to FY97. As a result of these multiple factors, our study showed a 30% decrease in total average direct hospital costs for carotid endarterectomy from $9974 to $7002 in this 4-year period. Infrainguinal bypass graft procedures showed a progressive decrease in total cost of 28% for patients without complications to $15,186 but remained unchanged for those with complications. Laboratory use, pharmacy use, and radiology use were not significantly different. CONCLUSIONS: Case management for patients undergoing carotid endarterectomy and infrainguinal bypass grafting involving an integrated team of vascular surgeons, surgical house staff, a dedicated vascular nurse, and a social work case manager resulted in dramatic reductions both in length of stay and hospital resource utilization. As these costs decreased, operating room expenses assumed increasing importance. Operating room costs account for 60% of the direct costs of carotid endarterectomy and a comparable percentage for uncomplicated infrainguinal bypass grafting. Further substantial reductions in direct hospital costs will depend primarily on reductions in operating room costs, particularly those related to length of time in the operating room.