Monocyte adhesion to human vein grafts: a marker for occult intraoperative injury?

OBJECTIVE: Monocyte adhesion to the vessel wall is believed to be an important initiating event in atherosclerosis and intimal hyperplasia. We hypothesized that occult intraoperative vein injury induces an immediate increase in monocyte adhesion that may be critical to the development of vein graft disease. METHODS: Vein segments were obtained from patients (n = 23) undergoing lower extremity bypass. The initial segment (V1, n = 17) was excised immediately at the time of conduit harvest. A second segment (V2, n = 23) was obtained from the distal conduit just before performing the distal anastomosis. Segments were incubated with radiolabeled THP-1 cells (monocytoid cell line) for 1 hour at 37 degrees C, then rinsed and solubilized for determination of bound radioactivity. In a subset of grafts (n = 4), THP-1 cells were preincubated with monoclonal antibody (mAB) 7E3 (which binds to the monocyte integrin Mac-1 at its fibrinogen [Fg]-binding site) or control (mAB 14E11). Fg deposition and endothelial coverage were evaluated by immunohistochemistry (n = 10). Statistical analysis was performed using the paired t test and analysis of variance. Follow-up graft patency data were obtained and correlated with adhesion values using an exact test (StatXact, Cytel Software, Cambridge, Mass). RESULTS: Monocyte adhesion was significantly increased after surgical manipulation (V1, 2400 +/- 770 versus V2, 7343 +/- 1555 cells/cm(2); P <.02). Fg deposition was abundant in V2 sections and not seen in V1. Monocyte adhesion to V2 segments was significantly reduced (58% of control, P <.01) by 7E3 treatment. Graft follow-up was complete with a mean interval of 11 months. Higher V2 adhesion values were associated with occluded grafts (P =.07). The median value for the six occluded grafts was 6234 cells/cm(2) versus 3892 cells/cm(2) for the 17 patent grafts. CONCLUSIONS: Monocyte adhesion to the vein wall is immediately increased after surgical manipulation and is inhibited by mAB 7E3. Early monocyte adhesion to vein grafts is likely to involve interactions between Mac-1 and Fg. Heightened levels of monocyte adhesion at implantation may be a marker for subsequent vein graft failure.

Arterial reconstruction for lower limb ischemia.

The treatment of advanced atherosclerosis involving the lower extremities has undergone considerable evolution over the last several decades. Current strategies hinge on an appreciation of the natural history of disease, the overall health status of the patient, and an armamentarium of endovascular and open surgical reconstructive techniques that may be tailored to optimize outcome for the individual patient. Patients with aorto-iliac disease have a variety of available options with generally good results. For infrainguinal disease, surgical bypass using autogenous vein is the mainstay of interventional therapy and will remain so for the foreseeable future. Increasing medical and surgical challenges are presented by this population, particularly as aggressive medical treatment of risk factors leads to an ongoing decline in cardiovascular mortality, combined with a dramatic increase in the prevalence of diabetes. The future, which is now already at hand, will bring the application of genomics, with a potential for altering the progression of disease as well as extending the long-term benefits of reconstruction.

Infrainguinal bypass grafting in patients with end-stage renal disease: improving outcomes?

OBJECTIVE: This study was undertaken to examine recent trends in the outcomes of patients with end-stage renal disease (ESRD) undergoing infrainguinal bypass grafting (IBG) with autogenous vein. METHODS: A retrospective analysis of all IBGs performed on patients with ESRD at a single tertiary care institution during the interval 1993 to 1999 was undertaken. The comparison groups consisted of concurrent series of patients with elevated creatinine (creatinine level > 1.2 mg/dL) and patients with normal renal function undergoing IBG. Procedural variables, angiographic runoff scores, and extent of tissue necrosis at presentation were correlated with outcome. Categoric parameters were compared with chi(2) analysis; rates were computed with life-table analysis. RESULTS: Of an overall cohort of 622 IBGs performed during this interval, 78 IBGs (12.5%) were performed on 60 patients with ESRD, with a perioperative mortality rate of 1.3% that was comparable to controls. All reconstructions in the ESRD cohort were for limb salvage indications. Four-year survival, primary, assisted primary, and secondary patency rates for the ESRD group were 51% +/- 9%, 60% +/- 11%, 86% +/- 5%, and 86% +/- 5%, respectively; these were not statistically different from the control groups. Limb salvage in the ESRD group was 77% +/- 6% at 4 years and was significantly less then either the elevated creatinine (92% +/- 4%; P <.02) or the normal renal function group (90% +/- 2%: P <.02). Of 16 amputations in the ESRD group, nine were performed in limbs with patent grafts. The only absolute predictor of limb loss despite a patent graft was the presence of a heel ulcer more than 4 cm in diameter. Age, runoff score of the International Society for Cardiovascular Surgery/Society for Vascular Surgery, isolated tibial bypass graft, and location of distal anastomosis were not predictive of hemodynamic failure. CONCLUSIONS: Patients with ESRD constitute an increasing proportion of patients undergoing IBG in a tertiary care setting. Four-year survival, perioperative mortality, and graft patency rates are similar to patients with normal renal function and support an aggressive approach to this population. Major limb amputation despite a patent graft remains a problem of unique frequency in patients with ESRD. Adequate predictors of hemodynamic failure of IBG in this group do not exist, although a heel ulcer more than 4 cm may indicate an unsalvageable foot.

Autogenous composite vein bypass graft for infrainguinal arterial reconstruction.

PURPOSE: Lower extremity arterial reconstruction in the absence of adequate greater saphenous vein remains a challenging problem in contemporary vascular practice. The purpose of this review is to evaluate the long-term results of autogenous composite vein grafts used for infrainguinal arterial bypass grafting. METHODS: We retrospectively evaluated a prospective vascular registry and reviewed inpatient and office records. RESULTS: From June 1983 to September 1999, 165 autogenous composite vein infrainguinal bypass grafts were performed in 154 patients (87 men, 67 women; mean age, 69 years). The mean follow-up was 25 months (range, 3-147). Patients had the usual risk factors, including a 30% incidence of prior coronary bypass grafting. Forty-eight percent of bypass grafts were performed after failed previous reconstructions, and 90% were performed for limb salvage. The conduits were comprised of 2 segments (75%), 3 segments (23%), and 4 segments (2%). The distal anastomosis was at the popliteal level in 17% and the tibial/pedal level in 83%. The 30-day operative mortality rate was 1.8%. Perioperative graft failure (< 30 days) occurred in 18 bypass grafts (11%), resulting in early amputation (< 30 days) in 1.2%. The overall 5-year cumulative patency rates were 44% +/- 5% for primary patency, 63% +/- 5% for primary-assisted patency (PAP), and 65% +/- 5% for secondary patency (SP). A high revision rate for stenosis or thrombosis was required during follow-up to maintain patency of the grafts (27%). Limb salvage was 81% +/- 5% at 5 years. Primary reconstructions with composite vein fared significantly better than secondary reconstructions (SP 76% vs 54% at 5 years, P <.01). Arm vein composites showed superior patency compared with greater saphenous vein composites (SP 79% vs 61% at 5 years, P <.05). CONCLUSIONS: Infrainguinal reconstruction with autogenous composite vein results in durable graft patency and limb salvage rates in patients with few alternatives for revascularization. Intensive graft surveillance with aggressive graft revision is necessary to achieve these results.

Impact of increasing comorbidity on infrainguinal reconstruction: a 20-year perspective.

OBJECTIVE: To examine trends in patient and procedural variables and outcomes associated with autogenous lower extremity arterial reconstruction (LER) in a single center during a period of two decades. SUMMARY BACKGROUND DATA: Surgical arterial reconstruction is of proven value in the therapy of patients with critical ischemia of the lower extremities. Changing demographics and increasing comorbidity are resulting in an increasing prevalence and associated complexity of peripheral vascular disease. The effect of these variables on the types and outcomes of surgical reconstructions is not known. METHODS: The authors performed a retrospective analysis of all autogenous LER procedures performed at their institution from 1978 to 1997. Procedures were divided into 5-year intervals: group 1, 1978 to 1982; group 2, 1983 to 1987; group 3, 1988 to 1992; group 4, 1993 to 1997. Categorical parameters were compared using chi-square analysis; rates were computed by the life-table method and compared using Mantel-Cox log-rank analysis. RESULTS: A total of 1,642 autogenous LER procedures were performed in 1,274 patients. A significant increase in age, female gender, diabetes mellitus, renal failure, and prior coronary artery bypass grafting was noted in group 4. Increased technical complexity in this group was reflected by a greater incidence of tissue necrosis as the indication for LER, the use of ectopic or composite vein, and more distal levels of outflow. The surgical death rate remained unchanged (2%) throughout. Patient survival, primary and secondary graft patency, and limb salvage at 5 years for the entire cohort were 70 +/- 2%, 63 +/- 2%, 73 +/- 1%, and 85 +/- 1%, respectively. Hospital length of stay was reduced 25% from a mean of 15.7 +/- 0.8 days in group 3 to 11.7 +/- 0.4 days in group 4. CONCLUSION: In a tertiary practice setting, patients requiring LER present an increasingly complex medical and surgical challenge compared with the previous decade. Excellent outcomes may still be achieved by an aggressive approach relying on autogenous vein conduit.

Infrainguinal arterial reconstructions with vein grafts in patients with prior aortic procedures: the influence of aneurysm and occlusive disease.

PURPOSE: This study assessed whether infrainguinal reconstructions with autogenous vein (IR) performed in patients with prior abdominal aortic aneurysm (AAA) repairs have altered graft patency, compared with those in patients who have undergone prior aortobifemoral bypass grafting procedures (ABF) for aortoiliac occlusive disease. METHODS: From 1979 to 1998, 54 patients with prior aortic reconstructions underwent 64 autogenous single-segment saphenous IRs solely for infrainguinal occlusive disease. Included in this cohort were 30 IRs with an earlier AAA repair and 34 IRs with an earlier ABF repair. During the same period, 1274 patients underwent 1642 autogenous vein lower-extremity bypass grafting procedures (LEB). Lower-extremity native arterial (AAA, n = 6; ABF, n = 11) and vein graft diameters (AAA, n = 6; ABF, n = 6) were determined by means of angiography and duplex ultrasonography, respectively. The three reconstruction groups (AAA, ABF, LEB) were compared. RESULTS: The patients in the three groups were similar in sex, indication for operation, proximal and distal anastomotic site, and number of distal runoff vessels. The cumulative 5-year primary graft patency rate in the AAA group (92% +/- 5%) was significantly higher (P <. 001) than that in the LEB group (63% +/- 2%) and the ABF group (44% +/- 11%). Furthermore, cumulative 5-year primary patency was decreased in the ABF group compared with the LEB group (P =.05). A significant increase in both native arterial (P =.001) and vein graft diameter (P <.05) was demonstrated by using linear regression and a Student t test, respectively, in the AAA group compared with the ABF group. CONCLUSION: These data demonstrate that, compared with those in patients without a previous aortic procedure, IRs in patients with prior AAA repairs have significantly improved graft patency, and IRs in patients with prior ABF reconstructions for aortoiliac occlusive disease have significantly decreased graft patency. Larger arterial diameter and altered vein graft adaptation may contribute to the superior long-term outcomes of IRs in patients with prior AAA repairs.

Ex-vivo gene therapy of human vascular bypass grafts with E2F decoy: the PREVENT single-centre, randomised, controlled trial.

BACKGROUND: Cell-cycle blockade by ex-vivo gene therapy of experimental vein grafts inhibits the neointimal hyperplasia and subsequent accelerated atherosclerosis that lead to human bypass-graft failure. In a prospective, randomised, controlled trial, we investigated the safety and biological efficacy of intraoperative gene therapy in patients receiving bypass vein grafts. METHODS: We studied gene therapy that uses decoy oligodeoxynucleotide, which binds and inactivates the pivotal cell-cycle transcription factor E2F. 41 patients were randomly assigned untreated (16), E2F-decoy-treated (17), or scrambled-oligodeoxynucleotide-treated (eight) human infrainguinal vein grafts. Oligonucleotide was delivered to grafts intraoperatively by ex-vivo pressure-mediated transfection. The primary endpoints were safety and inhibition of target cell-cycle regulatory genes and of DNA synthesis in the grafts. Analysis was by intention to treat. FINDINGS: Mean transfection efficiency was 89.0% (SD 1.9). Proliferating-cell nuclear antigen and c-myc mRNA concentrations and bromodeoxyuridine incorporation were decreased in the EF2-decoy group by medians of 73% [IQR 53-84], 70% [50-79], and 74% [56-83], respectively) but not in the scrambled-oligodeoxynucleotide group (p<0.0001). Groups did not differ for postoperative complication rates. At 12 months, fewer graft occlusions, revisions, or critical stenoses were seen in the E2F-decoy group than in the untreated group (hazard ratio 0.34 [95% CI 0.12-0.99]). INTERPRETATION: Intraoperative transfection of human bypass vein grafts with E2F-decoy oligodeoxynucleotide is safe, feasible, and can achieve sequence-specific inhibition of cell-cycle gene expression and DNA replication. Application of this genetic-engineering strategy may lower failure rates of human primary bypass vein grafting.

Improved graft patency and altered remodeling in infrainguinal vein graft reconstruction for aneurysmal versus occlusive disease.

PURPOSE: This study attempted to determine whether autogenous vein used for infrainguinal reconstruction in patients with aneurysmal disease might demonstrate an altered adaptive response compared with those patients who underwent reconstructive surgery for occlusive disease, potentially altering graft patency. METHODS: From 1974 to 1997, 43 patients underwent vein grafting for 60 popliteal artery aneurysms (PAA). RESULTS: In an attempt to monitor early vein graft adaptation, serial graft surveillance by Duplex ultrasound scan was performed in a statistically valid subset of age-, sex-, and distal anastomotic site-matched patients with PAA and patients with occlusive disease (OD; n = 8 PAA; n = 8 OD). Compared with an age-matched and sex-matched cohort of patients (n = 60 grafts in each group) with occlusive disease and who had femoral below-knee bypass grafts (FBP) only, patients undergoing infrainguinal reconstruction for PAA had a higher 5-year primary graft patency (92% +/- 4% for PAA vs 66% +/- 7% for FBP; P <.01). Duplex surveillance demonstrated a progressive increase in arterialized vein graft diameter in the PAA group versus the OD group. In univariant analysis, aneurysmal disease was a significant predictor of final follow-up diameter (P =.002). In a linear regression model, controlling for diameter at first follow-up after bypass grafting, first follow-up diameter was also predictive of final follow-up diameter. CONCLUSION: These data suggested altered remodeling of vein grafts in patients with popliteal artery aneurysm, which may have a beneficial effect on patency.

The effect of heart rate control on myocardial ischemia among high-risk patients after vascular surgery.

UNLABELLED: Patients undergoing vascular surgery have a high risk of suffering major postoperative cardiac events. Preoperative myocardial ischemia as detected by Holter monitoring identifies a high-risk subgroup whose postoperative ischemia, similarly detected, seems to herald major cardiac events. In this study, we determined whether systematic, patient-specific postoperative heart rate control with beta-adrenergic blocker therapy decreases the incidence of postoperative ischemia among high-risk vascular surgery patients. A total of 26 of 150 patients who underwent elective vascular surgery and were monitored preoperatively by 24-h Holter were found to have significant myocardial ischemia as defined by ST-segment depression. The minimal heart rate at which this ST-segment depression occurred was identified (ischemic threshold), and these 26 patients were then randomized to receive continuous i.v. beta-blockade with esmolol or placebo plus usual medical therapy, aiming to reduce the postoperative heart rate to 20% below the ischemic threshold. All patients were monitored by Holter for 48 h postoperatively. Postoperative Holter readings were analyzed for the incidence of ischemia and for the number of hours during which heart rate was controlled below the ischemia threshold. Patients had a median of two episodes of preoperative ischemia lasting a median of 30 min (range 1-155 min). A total of 15 patients were randomized to receive esmolol, and 11 were randomized to receive placebo. The two groups were comparable with respect to clinical characteristics and incidence and duration of preoperative ischemia. Ischemia persisted in the postoperative period in 8 of 11 placebo patients (73%), but only 5 of 15 esmolol patients (33%) (P < 0.05). Of the 15 esmolol patients, 9 had mean heart rates below the ischemic threshold, and all 9 had no postoperative ischemia. A total of 4 of 11 placebo patients had mean heart rates below the ischemic threshold, and 3 of the 4 had no postoperative ischemia. There were two postoperative cardiac events among patients who had postoperative ischemia (one placebo, one esmolol) and whose mean heart rates exceeded the ischemic threshold. Our data suggest that patient-specific, strict heart rate control aiming for a predefined target based on individual preoperative ischemic threshold was associated with a significant reduction and frequent elimination of postoperative myocardial ischemia among high-risk patients and provide a rationale for a larger trial to examine this strategy's effect on cardiac risk. IMPLICATIONS: Patients who undergo peripheral vascular surgery often experience transient cardiac complications and/or permanent heart damage just after surgery because of inadequate myocardial blood flow. In this study, we identified patients at high risk of cardiac complications after vascular surgery and showed that if their heart rate was carefully controlled for 48 h after surgery, myocardial ischemia, a common marker of heart injury, was markedly reduced.

Aerobic bacteria and solids in a three-tank, two-pass, counterflow scalder.

Scald water and whole carcass rinse samples were collected on 9 different d in a commercial broiler processing plant operating adjacent lines that processed birds from the same flock simultaneously. A conventional, single-tank, two-pass scalder was installed on one line and the other line had a three-tank, two-pass, counterflow scalder in which water mixed across the two lines of carcasses within each tank. Water samples from the turn around point in each tank were analyzed for aerobic bacteria and suspended solids. At the same time that water samples were taken, six carcasses were removed from the processing line immediately after feather removal and rinsed in 100 mL of phosphate-buffered saline; recovered rinse solution was analyzed for aerobic bacteria using a most probable number procedure. Estimated numbers of aerobic bacteria were significantly reduced in the third tank of the counterflow scalder compared to the second tank, or compared to the single tank of the conventional scalder. Despite the differences in aerobic bacteria between scald tanks, numbers of aerobic bacteria in carcass rinses were not affected by scalder design. Organic and total solids were significantly reduced in the third tank of the counterflow scalder compared to the first and second tanks, and in the third tank of the counterflow scalder compared to the conventional scalder. Solids in the third (final) tank of the counterflow scalder were reduced by about 70% compared to the conventional scalder.

Death of smooth muscle cells and expression of mediators of apoptosis by T lymphocytes in human abdominal aortic aneurysms.

BACKGROUND: Thinning of the tunica media and rarefaction of smooth muscle cells (SMCs) characterize aneurysmal aortas. Apoptosis determines the cellularity and morphogenesis of tissue. Macrophages and T lymphocytes infiltrate the wall of abdominal aortic aneurysms (AAAs) and produce death-promoting proteins (perforin, Fas, and FasL). This study investigated whether apoptosis occurs in association with the expression of these proteins. METHODS AND RESULTS: We examined signs of apoptosis and expression of death-promoting mediators in segments of AAAs from patients undergoing elective repair (n=20). Anti-alpha-actin immunostaining showed a reduced number of SMCs in AAAs. In situ terminal transferase-mediated dUTP nick end-labeling (TUNEL) showed higher levels of DNA fragmentation in AAAs than in controls (n=5). The AAA walls contained more cells bearing markers of apoptosis than normal aorta (P<0.05, Student's t test). Double immunostaining identified SMCs and macrophages as the principal cell types displaying fragmented DNA. Immunohistochemistry revealed that AAAs but not normal aorta contained CD4(+) and CD8(+) T cells that expressed well-characterized cytotoxic mediators: perforin, which produces membrane damage, and Fas, which acts by ligand-receptor interaction. Double immunostaining also identified SMCs that expressed Fas. Immunoblotting confirmed the presence and, in the case of Fas, activation of these proteins in aneurysmal tissue. CONCLUSIONS: Many medial SMCs in AAAs bear markers of apoptosis and signals capable of initiating cell death. Apoptotic death may contribute to the reduction of cellularity and to the impaired repair and maintenance of the arterial extracellular matrix in AAAs. Macrophages and T lymphocytes infiltrate the wall of AAAs, where they can produce cytotoxic mediators such as cytokines, perforin, and Fas/FasL. These death-promoting products of activated immune cells may contribute to elimination of SMCs, a source of elastin and collagen, during the pathogenesis of AAAs.

The impact of cardiac comorbidity after carotid endarterectomy.

PURPOSE: Myocardial infarction and other comorbidities contribute to complications after carotid endarterectomy (CEA). However, because the combined stroke and death rate after CEA is less than 5%, even relatively large series have small numbers of adverse events that preclude a detailed analysis of the association between the outcome and the patient factors, such as comorbidity and age. We sought to overcome this limitation by studying patients who underwent CEA in a large random sample of Medicare beneficiaries. METHODS: We used a database that contained a 20% random sample of all Medicare beneficiaries to identify patients who underwent CEA between the years 1988 to 1990 (n = 22,165), and we followed these cases until 1992. With multivariate logistic regression and Cox proportional hazards regression models, we examined the impact of age, race, gender, geographic location, hospital characteristics, and comorbidity, including acute myocardial infarction (AMI) and congestive heart failure (CHF), on the risk of stroke and death after CEA. RESULTS: AMI and CHF had the greatest negative impact on the long-term survival rates (adjusted hazard ratio [HR]: 2.40, P < .0001, and 2.85, P < .0001, respectively). Other variables with a significant impact on the long-term survival rates were an age of >80 years (HR, 2.16; P < .0001), an acute stroke (HR, 1.51; P < .0001), diabetes mellitus (DM; HR, 1.52; P < .0001), and male sex (HR, 1.32; P < .0001). In addition, AMI, CHF, DM, and advanced age were associated with an increased risk of perioperative stroke and death. CONCLUSION: Patients with AMI, CHF, DM, and an age of >80 years have diminished perioperative and long-term survival rates after CEA. These results may alter the risk/benefit analysis for such patients, especially those with asymptomatic disease.

Early operative intervention after thrombolytic therapy for primary subclavian vein thrombosis: an effective treatment approach.

PURPOSE: Effective treatment of primary subclavian vein thrombosis focuses on restoration of venous patency, relief of intrinsic stenosis, and decompression of the thoracic inlet. The appropriate method and timing for surgery, however, have not been not well defined. We conducted a study to determine an acceptable treatment approach. METHODS: A retrospective review evaluated 11 patients seen at our institution in an 8-year period. Seven patients were male and four were female, with an average age of 30 years (range 15 to 54 years). Two patients who had symptomatic stenosis without occlusion were omitted from the study. All patients with occlusion received urokinase therapy and underwent surgical decompression within 5 days of thrombolytic therapy. Five percutaneous transluminal angioplasties were attempted before operative intervention. Eleven decompressions were performed, including nine first-rib resections and two scalenectomies. Five operative venous procedures, consisting of thrombectomy with patch closure (n = 3) and bypass (n = 2), and seven venolysis procedures were performed. All patients received coumadin for 3 to 6 months after the operation. RESULTS: Urokinase therapy established wide venous patency in nine of the 11 extremities treated, with the remaining two requiring thrombectomy for residual thrombus at the time of operation. One patient who underwent transluminal angioplasty before the operation had rethrombosis, and the remaining four showed no improvement in venous stenosis after the intervention. Eight of nine extremities treated by first-rib resection and one of two treated by scalenectomy were free of residual symptoms at follow-up. CONCLUSIONS: Preoperative use of percutaneous balloon angioplasty is ineffective and should be avoided in this setting. Surgical intervention within days of thrombolysis obviates the need for interim oral anticoagulation and enables patients to return to normal activity sooner.