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Biomedical subjects

Frank W LoGerfo

Publications and source records attributed to Frank W LoGerfo.

At least 19 recordsLinked to original sources

Creatinine clearance but not serum creatinine alone predicts long-term postoperative survival after lower extremity revascularization.

BACKGROUND: Renal insufficiency is a well-described risk factor for perioperative morbidity and shortened survival after major vascular procedures. Due to the potential inaccuracy of serum creatinine levels alone in measuring kidney function, our aim was to determine whether estimated creatinine clearance more consistently predicted long-term survival. METHODS: A retrospective review of one institution's vascular registry was performed. Logistic regression analysis was conducted to determine independent predictors of 1-, 2- and 3-year postoperative mortality. Creatinine clearance was estimated as [140 - age (years)] x weight (kg)/72 x serum creatinine (mg/dl), multiplied by 0.85 for women. RESULTS: A total of 252 consecutive patients underwent infrainguinal bypass procedures between August 1999 and May 2000. Demographics included average age 68 years, 65% male, 74% diabetic, 12% dialysis-dependent, 23% history of congestive heart failure, 12% history of stroke and 20% serum creatinine >2 mg/dl. One-year mortality was 16% (n = 40), 2-year mortality was 25% (n = 64), and 3-year mortality was 35% (n = 88). There was no difference in serum creatinine values between survivors and non-survivors at 1 year (1.8 vs. 1.9, p = 0.80), 2 years (1.8 vs. 2.0, p = 0.62) or 3 years (1.8 vs. 2.0, p = 0.24), and creatinine >2 mg/dl did not predict long-term adverse outcomes. In contrast, reduced creatinine clearance (< or =60 ml/min) was an independent predictor of mortality regardless of dialysis status (1 year: OR = 2.53, p = 0.014; 2 years: OR = 2.46, p = 0.004; 3 years: OR = 2.45, p = 0.001), and creatinine clearance was higher for survivors versus non-survivors at all 3 time points (1 year: 70.2 vs. 49.5, p = 0.003; 2 years: 72.3 vs. 51.2, p < 0.0001; 3 years: 74.7 vs. 52.6, p < 0.0001). Other independent predictors of mortality included a history of stroke (1 year: OR = 3.28, p = 0.008; 2 years: OR = 2.55, p = 0.025; 3 years: OR = 2.35, p = 0.038) and congestive heart failure (1 year: OR = 2.86, p = 0.006; 2 years: OR = 2.54, p = 0.005; 3 years: OR = 2.13, p = 0.017). CONCLUSIONS: Independent of dialysis status, a decreased creatinine clearance, but not elevated serum creatinine alone, is an independent predictor of mortality after lower extremity arterial reconstruction. Determination of creatinine clearance should replace serum creatinine in the preoperative risk evaluations of patients undergoing major vascular surgical procedures.

Adult↗

Development of an infection-resistant, bioactive wound dressing surface.

Trauma, whether caused by an accident or in an intentional manner, results in significant morbidity and mortality. The goal of this study was to develop a novel biomaterial surface in vitro and ex vivo that provides both localized infection resistance nd hemostatic properties. Our hypothesis is that a combination of specific surface characteristics can be successfully incorporated into a single biomaterial. Functional groups were created with woven Dacron (Cntrl) material via exposure to ethylenediamine (C-EDA). The antibiotic ciprofloxacin (Cipro) was then applied to the C-EDA material using pad/autoclave technique (C-EDA-AB) followed by surface immobilization of the coagulation cascade enzyme thrombin (C-EDA-AB-Thrombin). Antimicrobial activity by the C-EDA-AB surface persisted for 5 days compared with Cntrl and dipped controls, which lasted <1 h. C-EDA-AB-Thrombin surfaces had 2.6- and 105-fold greater surface thrombin activity compared with nonspecifically bound thrombin and Cipro-dyed surfaces, respectively. Surface thrombus formation ex vivo was evident after 1 min of exposure, with thrombus organization evident by 2.5 min. In contrast, C-EDA-AB and Cntrl segments showed only blood protein adsorption on the fibers. Thus, this study demonstrated that Cipro and thrombin can be simultaneously incorporated onto a biomaterial surface while maintaining their respective biological activities.

Bacterial Infections↗

In vivo testing of an infection-resistant annuloplasty ring.

BACKGROUND: An infection-resistant surface incorporated into a prosthetic cardiac valve has great potential clinical applications. STUDY DESIGN: A sewing ring construct was created using ciprofloxacin-treated polyester. Then ciprofloxacin-treated and untreated constructs were implanted subcutaneously on the dorsum of rats and inoculated with Staphylococcus aureus. At 7, 14, and 30 days animals were sacrificed and the implants were retrieved. Each implant was assessed for frank purulence and gross tissue incorporation by a blinded observer. The implants were processed for conventional histology and examined by a blinded Pathologist. Ciprofloxacin-treated rings were also implanted in the absence of a bacterial challenge. At explantation, a maximal zone of inhibition, if present, was measured. Finally, ciprofloxacin was eluted with methanol from the explanted segments and the concentration of ciprofloxacin eluted was determined. RESULTS: Ciprofloxacin-treated sewing rings had greater gross tissue incorporation than untreated rings in the presence of a bacterial challenge (P=0.005). Ciprofloxacin-treated rings also had a lower incidence of frank purulence, but this did not reach statistical significance. After 14 days of implantation, ciprofloxacin treated rings had fewer neutrophils (P=0.018) and greater histological tissue incorporation (P=0.017) than untreated rings. The explanted ciprofloxacin-treated rings maintained a zone of inhibition of 3.0+/-1.0 mm after 1 day of implantation and 1.3+/-0.6 mm after 2 days. Ciprofloxacin could be eluted in significant quantities from the explanted rings after 7 days of implantation. CONCLUSIONS: Ciprofloxacin treated polyester can be incorporated into an annuloplasty ring construct that demonstrates excellent tissue incorporation and infection resistance. This study supports the use of this construct in the mitral position in a large animal model.

Animals↗

Timing of pedal bypass failure and its impact on the need for amputation.

Although the utility of dorsalis pedis (DP) bypass for limb ischemia has been well established, the fate of limbs with a failed bypass to the DP artery remains unclear. Data of all patients undergoing DP bypass grafting within a 12-year period from two university hospitals' vascular registries were retrospectively reviewed. Outcomes of early (<30 days) and delayed graft failure (>30 days) were examined. The Student's t-test and chi-squared test were used for univariate analysis; patency rates and patient survival were calculated using the Kaplan-Meier product limit method. Of 1434 DP bypass grafts, 277 (19.3%) failed grafts were identified. Sixty five (4.5%) grafts failed early (within 30 days of surgery) and 212 (14.8%) failed late at a mean time of 15.3 months (range, 1.5-105 months) after initial bypass. Of the 65 limbs with early graft failure, 28 (43.1%) proceeded directly to amputation and 20 underwent additional revascularization attempts, but limb salvage was achieved in only 7 patients; in 45 (69.2%) patients no further revascularizations were attempted. Seventy-four (34.9%) patients with late graft failure underwent redo revascularization. Thirty-nine (52.6%) had their limb saved with graft revision, but 35 patients (47.3%) ultimately lost their limb. In 138 patients with late graft failure (65.1%) no further revascularization attempts were performed. Sixty-two (44.9%) required major amputation. Overall, 49.8% of patients with failed pedal grafts ultimately suffered limb loss. Early graft failure resulted in a significantly higher rate of major amputation that did late graft failure (63.1% vs. 45.8%, respectively; p = 0.015). These results indicate that early occlusion of pedal bypass often leads to immediate major amputation and interventions to maintain graft patency in this setting are often futile. Late failure of pedal bypass is associated with a lower likelihood of amputation because of a higher rate of success of bypass revisions and a lower occurrence of critical ischemia with graft failure.

Aged↗

Major lower extremity amputation: outcome of a modern series.

HYPOTHESIS: Major lower extremity amputation results in significant morbidity and mortality. DESIGN: Retrospective database query and medical record review for January 1, 1990, to December 31, 2001. Mean follow-up was 33.6 months. SETTING: Academic tertiary care center. PATIENTS: Nine hundred fifty-nine consecutive major lower extremity amputations in 788 patients, including 704 below-knee amputations (BKAs) (73.4%) and 255 above-knee amputations (AKAs) (26.6%). MAIN OUTCOME MEASURES: Patient survival, cardiac morbidity, infectious complications, and subsequent operation. RESULTS: Overall 30-day mortality was 8.6%, worse for AKA (16.5%) than BKA (5.7%) patients (P<.001). Thirty-day mortality for guillotine amputation for sepsis control was 14.3% compared with 7.8% for closed amputation (P =.03). Complications included cardiac (10.2%), wound infection (5.5%), and pneumonia (4.5%). Twelve AKA (4.7%) and 129 BKA (18.4%) limbs required subsequent operation. Only 66 BKAs (9.4%) required conversion to AKA (average, 77.1 days postoperatively). Overall survival was 69.7% and 34.7% at 1 and 5 years, respectively. Survival was significantly worse for AKAs (50.6% and 22.5%) than BKAs (74.5% and 37.8%) (P<.001). Survival in patients with diabetes mellitus (DM) was 69.4% and 30.9% vs 70.8% and 51.0% in patients without DM at 1 and 5 years, respectively (P =.002). Survival in end-stage renal disease patients was 51.9% and 14.4% vs 75.4% and 42.2% in patients without renal failure at 1 and 5 years, respectively (P<.001). CONCLUSIONS: Major amputation continues to result in significant morbidity and mortality. Survivors with BKA require revision or conversion to AKA infrequently. Long-term survival is dismal for patients with DM and end-stage renal disease and those undergoing AKA.

Adult↗

Temporal gene expression following prosthetic arterial grafting.

BACKGROUND: Following prosthetic arterial grafting, cytokines and growth factors released within the perianastomotic tissues stimulate smooth muscle cell proliferation and matrix production. While much in vitro work has characterized this response, little understanding exists regarding the sequential up- and down-regulation of genes following prosthetic arterial grafting. This study evaluates temporal gene expression at the distal anastomosis of prosthetic arterial grafts using microarray analysis. METHODS: Expanded polytetrafluoroethylene (ePTFE) carotid interposition grafts (n = 12) were surgically implanted into mongrel dogs. Distal anastomotic segments were harvested at 7, 14, 30, or 60 days. Contralateral carotid artery served as control. Total RNA was isolated from the anastomotic tissue and paired controls. Samples were probed with oligonucleotide microarrays consisting of approximately 10000 human genes to analyze differential gene expression at each time point. RESULTS: Forty-nine genes were found to be up-regulated and 37 genes were found to be down-regulated at various time points. Six genes were found to be consistently up-regulated at all time intervals, including collagen type 1 alpha-1 and alpha-2, 80K-L protein (MARCKS), and osteopontin. Six genes were found to be consistently down-regulated, including smoothelin and tropomyosin 2. RT-PCR and immunohistochemistry confirmed the microarray data. CONCLUSIONS: This study uses microarray analysis to identify genes that were temporally up- and down-regulated after prosthetic arterial grafting. Genes with similar patterns of expression have been identified, providing insights into related cellular pathways that may result in the formation of anastomotic intimal hyperplasia.

Anastomosis, Surgical↗

Popliteal artery aneurysms: a comparison of outcomes in elective versus emergent repair.

OBJECTIVE: The purpose of this study was to assess and compare outcomes of elective versus emergent operative repair of popliteal artery aneurysms. DESIGN: A retrospective analysis of a prospectively recorded vascular surgery database from June 1992 to December 2002 was performed with chart review. Main outcome measures Patient survival, limb salvage, and graft patency were evaluated. RESULTS: Fifty-one popliteal artery aneurysms were repaired in 39 patients, all male and ranging in age from 18 to 87 years (mean 67.1). Mean follow-up was 47.8 months. Repair was elective in 37 (72.5%) and emergent in 14 (27.5%) limbs, 13 with acute ischemia and one with aneurysm rupture. Thrombolytic therapy was utilized in four ischemic limbs with no suitable bypass target vessel identified on initial arteriogram. Outflow vessels included the popliteal artery in 22 (43.1%) and infrapopliteal vessels in 29 (56.9%) limbs. Cardiac morbidity and 30-day mortality rates were 0%. Overall primary patency, secondary patency, limb salvage, and actuarial survival were 95.6%, 100%, 98.0%, and 98.0% at 1 year and 85.1%, 96.9%, 98.0%, and 83.8% at 5 years, respectively. Bypass graft redo or revision was performed for stenosis in one and occlusion in four limbs. Two amputations were performed at 6 days and 63.6 months after initial aneurysm repair. No difference was noted between elective and emergent groups with regard to patency, limb salvage, or survival (P >.26), and no association between the number of identified target vessels and limb salvage or patency was demonstrated (P =.12). CONCLUSION: In our experience, the outcome of the popliteal artery aneurysm repair was comparable in the emergent and elective settings. Aggressive tibial reconstruction plays a crucial role in the treatment of popliteal artery aneurysms, especially in those presenting with acute limb ischemia. Thrombolytic therapy is infrequently required in the acute setting, although it may be useful in patients with no identifiable outflow target vessel on initial arteriogram.

Adolescent↗

Bypass to plantar and tarsal arteries: an acceptable approach to limb salvage.

OBJECTIVE: This study was undertaken to evaluate our experience with distal arterial bypass to the plantar artery branches and the lateral tarsal artery for ischemic limb salvage. METHODS: This was a retrospective analysis of data prospectively entered into our vascular surgery database from January 1990 to January 2003 for all consecutive patients undergoing bypass grafting to the plantar artery branches or the lateral tarsal artery. Median follow-up was 9 months (range, 1-112 months). Demographic data, indications for surgery, outcomes, and patency were recorded, and statistical analysis was performed to assess significance. RESULTS: Ninety-eight bypass procedures to either the medial plantar artery, lateral plantar artery, or lateral tarsal artery were performed in 90 patients. Eighty-one patients (83%) were men. Mean age was 67.5 +/- 11.6 years. Indications for operation were tissue loss in 93 patients (95%), rest pain in 3 patients (3%), and failing graft in 2 patients (2%). Eighteen patients (18%) had previously undergone vascular reconstruction, and 5 patients (5%) had undergone previous bypass to the dorsalis pedis artery. Seventy-one grafts (72%) had inflow from the popliteal artery, 25 grafts had inflow from a femoral artery or graft (26%), and 2 grafts had inflow from a tibial artery (2%). Conduits used were greater saphenous vein in 67 patients (69%), arm vein in 20 patients (20%), composite vein in 10 patients (10%), and polytetrafluoroethylene conduit in 1 patient (1%). There were 77 bypasses (79%) to plantar artery branches, and 21 bypasses (21%) to the lateral tarsal artery. Thirty-day mortality was 1% (1 of 98 procedures). Early graft failure within 30 days occurred in 11 patients (11%). In the subset of patients with a previous arterial reconstruction, there were 2 early graft failures within 30 days (11%). Both occurred in patients who had undergone previous bypass to the dorsalis pedis artery. Primary patency, secondary patency, limb salvage, and patient survival were 67%, 70%, 75%, and 91%, respectively, at 12 months, and 41%, 50%, 69%, and 63%, respectively, at 5 years, as determined from Kaplan-Meier survival curves. Greater saphenous vein grafts performed better than all other conduits, with a secondary patency rate of 82% versus 47% at 1 year (P = .009). CONCLUSION: Inframalleolar bypass to plantar artery branches and the lateral tarsal artery, even in patients with a previously failed revascularization, can be undertaken with acceptable patency and limb salvage rates. Early graft failure, however, is higher, whereas patency and limb salvage rates are lower, compared with bypass to the dorsalis pedis artery. The use of saphenous vein as a conduit results in the best patency for plantar or lateral tarsal bypass procedures.

Aged↗

Recurrent stenosis and contralateral occlusion: high-risk situations in carotid endarterectomy?

Carotid angioplasty and stenting (CAS) has been proposed as a treatment option for carotid occlusive disease in high-risk patients including those with recurrent stenosis (RS) and contralateral occlusion (CO). This study reviews the results of carotid endarterectomy (CEA) in patients with RS and CO. We conducted a retrospective review from our vascular registry of 1670 patients who underwent CEAs ( n = 1950) from January 1990 through December 2001. Procedures included RS 86 (4.4%), CO 112 (5.7%), and control 1752 (89.9%). There were 37 strokes in the entire group (1.9%). Among the high-risk group with RS and CO, there were 6 strokes, (RS n = 2, CO n = 4) 3%. There were 31 strokes in the control group 1.8% ( p = NS). Postoperative TIAs were observed more frequently in patients with CO ( n = 2) or RS ( n = 2), 1.8% and 2.3%, respectively ( p < 0.05). Neck hematomas, intracerebral hemorrhages, and myocardial infarctions did not differ between groups. Three deaths occurred within 30 days (0.15%); one was a patient with CO. Renal failure and symptomatic disease were each associated with a higher risk of perioperative stroke; among patients with renal failure there were 6 strokes (4.6%) p < 0.05, in symptomatic patients there were 26 strokes (2.7%) p < 0.05. Multivariate logistic regression analysis confirmed that preoperative renal disease and surgery for symptomatic disease were both significant predictors of perioperative stroke ( p < 0.05; odds ratio 2.177 and 2.943 respectively) while neither RS nor CO was from these results we concluded that the presence of RS and CO do not increase the risk of perioperative stroke in CEA.

Angioplasty, Balloon↗

Outcome of lower-extremity revascularization in patients younger than 40 years in a predominantly diabetic population.

OBJECTIVE: Incidence of perioperative complications is increased and outcome is poor in young patients undergoing vascular surgery. We extensively reviewed results of lower-extremity procedures in this group of patients to further define the extent of short-term and long-term morbidity. METHODS: Results from our vascular registry were retrospectively reviewed for 76 lower-extremity revascularization procedures performed between January 1990 and May 2000 in 51 patients younger than 40 years. This represents 1.88% of 4052 lower-extremity bypass procedures performed during this period. Perioperative cardiac complications, long-term survival, graft patency, and limb salvage were evaluated. Kaplan-Meier curves were generated, and their significance was determined with the Cox-Mantel test. RESULTS: Forty-nine percent of patients were male, and 51% were female; mean age at presentation was 35.9 years (range, 27.5-39.8 years). Preoperative morbidity included diabetes mellitus (96.1%), smoking (70.6%), hypertension (78.4%), coronary artery disease (37.3%), hyperlipidemia (33.3%), and renal dysfunction (52.9%). Overall rate for 30-day postoperative mortality was 0.0%, for myocardial infarction was 0.0%, and for congestive heart failure was 1.32%. Thirty-day graft failure was 11.1% (n = 9). At 1 year, primary patency was 71.0%, secondary patency was 82.5%, and limb salvage was 87.1%; and at 5 years these rates were 51.9%, 63.4%, and 77.2%, respectively. After the initial surgery 11.8% (n = 6) of patients required at least one additional ipsilateral revascularization procedure, 31.3% (n = 16) required a bypass graft in the contralateral limb, and 23.5% (n = 12) ultimately required amputation. In patients who required additional ipsilateral procedures, 1-year primary patency rate was 66.7%, secondary patency rate was 62.5%, and limb salvage rate was 77.8%, compared with 5-year rates of 44.4%, 41.7%, and 64.8%, respectively, representing a decrease in patency compared with primary revascularization procedures. Overall survival at 1 year was 88.2%, compared with 73.3% at 5 years. Patients with preexisting renal disease had significantly decreased survival at 5 years compared with those without renal dysfunction (64.5% vs 82.6%; P =.019). CONCLUSIONS: Our data suggest that age younger than 40 years is not associated with increased perioperative morbidity and mortality. However, these patients have a significant rate of early graft failure and dismal long-term survival, especially in patients with preexisting renal dysfunction. In addition, ipsilateral repeat operations have a marginal success rate.

Adult↗

Poly(ADP-Ribose) polymerase is activated in subjects at risk of developing type 2 diabetes and is associated with impaired vascular reactivity.

BACKGROUND: We have previously shown that endothelial function is impaired not only in diabetes but also in subjects at risk of developing type 2 diabetes. We hypothesized that changes in the expression or activity of the endothelial isoform of nitric oxide synthase (eNOS), the receptor for advanced glycation end products (RAGE), and poly(ADP-ribose) polymerase (PARP) are related to this impairment. METHODS AND RESULTS: We included a control group of 21 healthy subjects, a group of 22 healthy individuals with parental history of type 2 diabetes, a group of 23 subjects with impaired glucose tolerance, and a group of 21 type 2 diabetic patients. Two 2-mm forearm skin biopsies were taken from each participant and used for measurements. The percentage of PARP-positive endothelial nuclei was higher in the group with parental history of type 2 diabetes and diabetic patients compared with the controls (P<0.001). Immunoreactivity for nitrotyrosine (a marker of reactive nitrogen species) was higher in the diabetic group compared with all other groups (P<0.01). No differences in the expression of eNOS and RAGE were found among all 4 groups. The polymorphism of the eNOS gene was also studied and was not found to influence eNOS expression or microvascular functional measurements. CONCLUSIONS: PARP activation is present in healthy subjects at risk of developing diabetes as well as in established type 2 diabetic patients, and it is associated with impairments in the vascular reactivity in the skin microcirculation.

Acetylcholine↗

A comparison of antegrade and retrograde mesenteric bypass.

Mesenteric artery bypass originating from the supraceliac aorta (antegrade bypass) has been the standard orientation of visceral artery bypass grafts. Retrograde bypass, in which the bypass originates from the iliac arteries, has not been as widely accepted. The purpose of our study was to compare the results of these two types of bypass in a similar population. We retrospectively reviewed the records of patients undergoing mesenteric artery bypass at two tertiary care medical centers (UCLA Medical Center, Beth Israel Deaconess Medical Center). Between February 1992 and January 2001, 37 patients underwent 39 mesenteric bypass procedures. The choice of bypass orientation (antegrade versus retrograde) was determined by the individual surgeon. Chart review, duplex ultrasonography, and/or telephone interviews were used to assess symptom-free survival. Actuarial analysis was completed using Kaplan-Meier survival estimates. From this assessment we were able to determine that symptom-free survival of patients undergoing retrograde mesenteric bypass is similar to that seen in antegrade bypass. Primary retrograde bypass is a valid option for patients undergoing mesenteric bypass.

Aged↗

Vascular smooth muscle cells derived from atherosclerotic human arteries exhibit greater adhesion, migration, and proliferation than venous cells.

BACKGROUND: Phenotypic variation of vascular smooth muscle cells (VSMC) may result in altered biological behavior and responses. Within the vessel wall, arterial VSMC have a greater propensity to form atherosclerotic lesions as compared to venous VSMC. In this study the rates of proliferation, adhesion, and migration were compared between VSMC of atherosclerotic arterial and venous origin. MATERIALS AND METHODS: Human VSMC cultures were isolated from 18 infragenicular arteries at the time of below knee amputation and from 20 saphenous veins during lower extremity revascularization surgery. Cell cultures were isolated from the media of each specimen and maintained in distinct cell lines for all assays. Cells from passages 2 and 3 were assayed for their proliferative capacity using total DNA fluorescence photometry and for adhesion and migration using a modified Boyden chamber. RESULTS: Patient age and the incidence of atherosclerotic risk factors did not vary significantly between the arterial and the venous patient groups. VSMC of atherosclerotic arterial origin demonstrated greater proliferation (arterial, 162 +/- 59 absorption units, vs. venous, 106 +/- 56 absorption units, P < 0.001), adhesion (arterial, 74.1 +/- 22.6 cells/microscopic field, vs. venous, 41.3 +/- 12.8 cells/microscopic field, P < 0.001) and migration (arterial, 427 +/- 185 cells/microscopic field, vs venous, 119 +/- 101 cells/microscopic field, P < 0.001) than VSMC of venous origin. CONCLUSION: Human atherosclerotic arterial VSMC exhibit significantly increased rates of proliferation, adhesion, and migration as compared to human venous VSMC. These observations of VSMC in culture are consistent with the clinical predilection for the hyperplasic responses that result in the development of atherosclerosis in the arterial wall. Possible intrinsic differences in VSMC phenotype should be considered in designing methods to limit atherosclerosis.

Aged↗

Lack of association of diabetes with increased postoperative mortality and cardiac morbidity: results of 6565 major vascular operations.

HYPOTHESIS: A number of preoperative factors, including diabetes mellitus (DM), have been cited as increasing risk in patients undergoing major vascular operations. In smaller studies at our institution we have not found this to be apparent. This study reviewed all major vascular operations to confirm our bias that DM is not associated with increased mortality or cardiac morbidity. DESIGN: Case series retrospectively reviewed from a vascular registry established in 1990. SETTING: Tertiary care center. PATIENTS: Consecutive sample of 6565 patients who underwent lower extremity revascularization or carotid or aortic procedures, grouped by presence or absence of DM. MAIN OUTCOME MEASURES: Postoperative mortality, congestive heart failure, or myocardial infarction. RESULTS: Patients with DM made up 62.3% of the population, and those without diabetes, 37.7%. Average age of the DM group was 67.1 years, with 61.3% male and 38.7% female. Average age of the non-DM group was 70.6 years, with 61.8% male and 38.2% female. The rates of overall postoperative mortality, myocardial infarction, and congestive heart failure were 1.14%, 1.59%, and 1.13%, respectively. Comparing the DM with the non-DM group, these rates were 0.96% vs 1.46%, 1.77% vs 1.30%, and 1.13% vs 1.14%, respectively. Using multivariate analysis, the DM group had an inverse relationship to perioperative death, with an odds ratio of 0.53 (P =.01). The factors that were associated with increased mortality were hemodialysis and history of congestive heart failure. Previous myocardial infarction was the only factor that predicted postoperative myocardial infarction. Kaplan-Meier survival curves showed a significantly decreased survival in the DM group during the next 5 years (P<.001). CONCLUSIONS: Diabetes alone does not confer a higher mortality or cardiac morbidity rate with major vascular procedures. However, long-term survival is significantly worse in this group of patients.

Adolescent↗

A biologically active VEGF construct in vitro: implications for bioengineering-improved prosthetic vascular grafts.

Prosthetic arterial grafts are unable to develop an intact endothelial lining after implantation, predisposing them to fail. Strategies have been sought to enhance endothelialization using growth factors and cytokines. This study assessed the biologic activity of vascular endothelial growth factor (VEGF) covalently linked to bovine serum albumin (BSA). Native and modified VEGF were assayed for endothelial cell migration and proliferation. Migration assays were performed comparing the effects of 2% fetal bovine serum (FBS), 50 ng/mL, 100 ng/mL, and 200 ng/mL of native VEGF and VEGF-BSA. Proliferation assays were performed by using Alamar Blue comparing cellular growth in 1% FBS, 10% FBS, 100 ng/mL unbound VEGF, and 100 ng/mL VEGF-BSA. VEGF is a potent chemotactic agent for endothelial cells in both unbound and bound states. Native VEGF solutions (50 ng/mL, 100 ng/mL, and 200 ng/mL) stimulated 23.9 cells/high power field (HPF), 35.3 cells/HPF, and 49.1 cells/HPF (p < 0.005). VEGF-BSA solutions stimulated 25.9 cells/HPF, 39.1 cells/HPF, and 69.0 cells/HPF (p < 0.001). VEGF-BSA and native VEGF supported similar increased cellular proliferation compared with 1% FBS media (p < 0.002). Modified VEGF retains its chemotactic and proliferative properties in vitro. These findings suggest that bare prosthetic surfaces lined with VEGF bound to a "basecoat" albumin may support endothelial cell proliferation and migration and thereby offer new strategies to improve graft patency.

Blood Vessel Prosthesis↗

Cutaneous microcirculation in the neuropathic diabetic foot improves significantly but not completely after successful lower extremity revascularization.

OBJECTIVE: The purpose of this study was the examination of the effect of successful large vessel revascularization on the microcirculation of the neuroischemic diabetic foot. RESEARCH DESIGN AND METHODS: We measured the cutaneous microvascular reactivity in the foot in 13 patients with diabetes with peripheral arterial disease and neuropathy (group DI) before and 4 to 6 weeks after successful lower extremity arterial revascularization. We also compared them with age-matched and sex-matched groups of 15 patients with diabetes and neuropathy, seven patients without neuropathy, and 12 healthy patients for control. We used single-point and laser Doppler scan imaging for the measurement of the foot skin vasodilatation in response to heating to 44 degrees C and to iontophoresis of 1% acetylcholine (endothelial-dependent response) and 1% sodium nitroprusside (endothelial-independent response). RESULTS: The group DI response to heat increased from 289% +/- 90% before surgery (percent increase over baseline measured in volts) to 427% +/- 61% (P <.05) after surgery but was still comparable with the response of the patients with diabetes and neuropathy (318% +/- 51%) and lower than the responses of the patients without neuropathy (766% +/- 220%) and the healthy patients for control (891% +/- 121%; P <.0001). The group DI acetylcholine response also improved from 6% +/- 4% before surgery to 26% +/- 8% after surgery (P <.05) and was similar to the responses of patients with diabetes and neuropathy (18% +/- 3%) and patients without neuropathy (38% +/- 8%) but still lower when compared with the response of the patients for control (48% +/- 9%; P <.001). The sodium nitroprusside response for group DI improved from 10% +/- 4% to 29% +/- 9% (P <.05) and was similar to the responses of the neuropathic (25% +/- 9%), nonneuropathic (32% plus minus 6%), and control (40% +/- 5%) groups. The group DI neurovascular response, which depends on the healthy function of the C-fiber nociceptors, was similar at baseline (5% +/- 9%) and after surgery (14% +/- %10) and in the neuropathic group (33% +/- 21%), but it was dramatically reduced when compared with the nonneuropathic (110% +/- 40%) and control (198% +/- 54%) groups (P <.001). CONCLUSION: Impaired vasodilation in the diabetic neuropathic lower extremity leads to functional ischemia, which improves considerably but is not completely corrected with successful bypass grafting surgery. Therefore, patients with diabetes and neuropathy may still be at high risk for the development of foot ulceration or the failure to have an existing ulcer heal despite adequate correction of large vessel blood flow.

Acetylcholine↗