All-trans-retinoic acid decreases cell proliferation and increases apoptosis in an animal model of vein bypass grafting.

BACKGROUND: We have previously demonstrated a decrease in intimal hyperplasia in vein bypass grafts from animals treated with all-trans-retinoic acid (atRA). The purpose of this study was to examine the effect of atRA on proliferation and apoptosis rates in healing vein bypass grafts. METHODS: Interposition jugular vein bypass grafts were placed in the carotid artery of 30 New Zealand white rabbits. Animals received either atRA (10 mg/kg/d) or vehicle (corn oil) for a period of 2 weeks. Animals were killed at 3, 7, or 28 days after graft placement after having received 3 doses of 5-bromo-2'-¿Deoxyuridine (BRDU, 35 Mg/KG). Animals Were Perfusion Fixed, And Vein Grafts Were Prepared For Immunohistochemistry By Using Antibodies To Brdu, Proliferating Cell Nuclear Antigen, And Bcl-XL. Apoptosis Was Measured By Using The Tunel Assay. Histologic Sections Were Analyzed By A Pathologist Blinded To The Study, And An Index Of Positively Stained Cells Was Generated For Each Layer Of The Vein Graft Wall. RESULTS: All-trans-retinoic acid reduced the proliferation index in the neointima of vein grafts during the first week after surgery. Apoptotic rates were higher in the intima of vein grafts from animals treated with atRA, which could not be explained by changes in bcl-xl expression. No differences were noted in the media or adventitia between the groups. CONCLUSIONS: atRA decreased cell proliferation and increased apoptosis in the intima of healing vein bypass grafts. These effects contribute to decreased intimal hyperplasia, which has been previously noted.

Intraoperative carotid evaluation.

HYPOTHESIS: Intraoperative duplex scanning can identify technical defects and increase the quality of carotid artery repair. DESIGN: We evaluated 100 consecutive carotid operations in 96 patients (60 men and 36 women) from 1995 to 1998. Spectral-derived peak systolic flow velocities (PSV) were graded (PSV < 100 cm/s, normal laminar flow; PSV 100-150 cm/s, mild or moderate flow disturbance; PSV > 150 cm/s, severe flow disturbance). Prospective criteria for intraoperative revision included PSV greater than 150 cm/s, spectral broadening, and B-mode imaging of intimal flaps or intraluminal debris. Preoperative, intraoperative, and 6-week follow-up duplex scan results were analyzed. SETTING: All patients were evaluated and treated at a single academic institution. INTERVENTIONS: All procedures were performed with the patient under general endotracheal anesthesia; 86% underwent shunting and 70% underwent patching. MAIN OUTCOME MEASURE: Number and type of revisions, patency of repair, residual and recurrent stenosis, and ipsilateral neurologic events. RESULTS: There were 33 intraoperative duplex studies with abnormal findings. Seven involved the common carotid artery and resulted in intraoperative revision of 5 intimal flaps at the site of the proximal clamp. In 11 patients, incomplete eversion endarterectomy resulted in elevated distal intimal flaps in the external carotid artery that were repaired through a separate arteriotomy. There were 15 abnormalities in the internal carotid artery prompting 5 revisions. Five studies with PSV of 100 to 150 cm/s had no defects on B-mode imaging and were observed without treatment. Five false-positive studies were attributed to increased flow velocity due to contralateral occlusive discase. At 6 weeks' follow-up, 4 of 5 repaired common carotid arteries were normal on duplex scan and 1 had a mild residual stenosis. Ten of the 11 external carotid repairs were patent and 1 was occluded. Four of the 5 internal carotid artery repairs were normal on postoperative evaluation and 1 had a mild residual stenosis. Of the 10 abnormal internal carotid arteries that were observed, 9 were normal on postoperative duplex and 1 had a mild residual stenosis. One perioperative stroke occurred in a patient with a normal, patent carotid repair. CONCLUSIONS: Intraoperative duplex evaluation of carotid reconstruction is an efficient, sensitive tool that can detect technical lesions that will jeopardize surgical reconstruction. Interpretive judgment is required because all flow disturbances do not dictate surgical intervention. This technique enables the surgeon to maximize the quality of the arterial reconstruction during carotid artery surgery.

Lessons learned in adopting endovascular techniques for treating abdominal aortic aneurysm.

HYPOTHESIS: Endovascular exclusion of abdominal aortic and common iliac aneurysms can be performed safely, and in the short term represents a feasible alternative to traditional, open aneurysm repair. PATIENTS AND METHODS: Forty-one patients were treated with endovascular grafts for 39 abdominal aortic and 2 common iliac artery aneurysms. RESULTS: All devices were successfully deployed. The size of the abdominal aortic aneurysms varied from 4.9 to 11.9 cm (average, 6.13 cm). The median procedure time was 195 minutes. There was one iliac artery rupture, which required celiotomy for repair. The hospital stay varied from 2 to 39 days (average, 6.7 days). The perioperative mortality rate was 2.4%. Sixteen patients (39%) had groin wound complications. Ten patients (24%) had evidence of contrast (endoleak) within the aneurysm sac on completion of the procedure. There were no obvious direct leaks from either the point of proximal or distal fixation. Seven of these endoleaks have resolved spontaneously. Two patients required additional procedures in the postoperative period to treat endoleak. The final patient has evidence of persistent endoleak on 3-month surveillance computed tomography scan. Major late problems occurred in 3 patients. CONCLUSION: Patients with large abdominal aortic aneurysms and considerable cardiac comorbidity can safely undergo endovascular aneurysm repair. Femoral groin wound complications resulting in prolonged hospitalization remain the major cause of perioperative morbidity. In contradistinction to open aneurysm repair, long-term surveillance is essential to detect migration of the device and identify flow within the residual aneurysm sac-complications that could lead to aneurysm rupture following endovascular repair.

Late development of esophageal compression from a vascular ring.

Severe esophageal compression due to a vascular ring rarely develops after childhood. We report a case of a 57-year-old man with recent onset of dysphagia associated with right aortic arch, right descending aorta, and retroesophageal left subclavian artery arising from an arch diverticulum. Surgical repair was recommended for relief of symptoms and to prevent rupture of the diverticulum. The patient underwent left thoracotomy, division of the ligamentum arteriosum, and excision of the arch diverticulum. The left subclavian artery was reimplanted into the left common carotid artery through a separate neck incision. The patient had total relief of dysphagia postoperatively.

Role of eicosanoids and white blood cells in the beneficial effects of limited reperfusion after ischemia-reperfusion injury in skeletal muscle.

Limiting the rate of reperfusion blood flow has been shown to be beneficial locally in models of ischemia-reperfusion injury. We investigated the effects of this on eicosanoids (thromboxane B2, 6-keto-PGF1 alpha, and leukotriene B4), white blood cell activation, and skeletal muscle injury as quantitated by triphenyltetrazolium chloride and technetium-99m pyrophosphate after ischemia-reperfusion injury in an isolated gracilis muscle model in 16 anesthetized dogs. One gracilis muscle in each dog was subjected to 6 hours of ischemia followed by 1 hour of limited reperfusion and then by a second hour of normal reperfusion. The other muscle was subjected to 6 hours of ischemia followed by 2 hours of normal reperfusion. Six dogs each were used as normal reperfusion controls (NR) and limited reperfusion controls (LR), with 5 dogs being treated with a thromboxane synthetase inhibitor (LR/TSI) and another five with a leukotriene inhibitor (LR/LI). LR in all three groups (LR, LR/TSI, and LR/LI) showed a benefit in skeletal muscle injury as measured by triphenyltetrazolim chloride and technetium-99m pyrophosphate when compared with NR. However, there was no significant difference between the groups with LR regarding eicosanoid levels and white blood cell activation when compared with NR. These results demonstrate that LR produces benefits by mechanisms other than those dependent upon thromboxane A2, prostacyclin, or white blood cell activation.

Outcome and expansion rate of 57 thoracoabdominal aortic aneurysms managed nonoperatively.

BACKGROUND: The prognosis of thoracoabdominal aortic aneurysms (TAAAs) managed nonoperatively is unknown. PATIENTS AND METHODS: To determine the risk of rupture and survival, we retrospectively reviewed the clinical course and computed tomographic data of 57 patients who were evaluated for degenerative, nondissecting TAAAs. Nonoperative management was decided initially for all patients. Data of aneurysm expansion rate were available in 29 patients who underwent 2 or more scans. Follow-up was complete in 52 (91%) patients and averaged 37 months (range 1 to 82). RESULTS: Thirty-four of the 57 (60%) patients died during follow-up, including 3 of 15 patients who underwent subsequent repair of their aneurysm. Two- and 5-year survival rates for the entire group were 69% and 39%, with repair-free survival rates of 52% and 17%, respectively. Eight (14%) aneurysms ruptured, accounting for 24% (8/34) of the deaths. Two- and 4-year risks of rupture were 12% and 32%, respectively. The median expansion rate was 0.2 cm/y and was greater in patients with chronic obstructive pulmonary disease (P < 0.05). All ruptured aneurysms were > 5 cm in diameter. Aneurysms with a diameter > 5 cm at diagnosis had a higher rupture rate than those with a diameter < or = 5 cm (P < 0.05). Expansion rate did not predict rupture. CONCLUSIONS: Mortality of patients with TAAAs preselected for nonoperative management is high, with an overall survival rate of 39% and repair-free survival rate of only 17% at 5 years. Expansion rate of TAAAs (0.2 cm/y) is similar to that of abdominal aortic aneurysms. Our data that support nonoperative management for patients with TAAAs < 5 cm in diameter, but confirm the increase rate of rupture for aneurysms > 5 cm.

PTFE shunts for hemodialysis access: progressive choice of configuration.

The autologous arteriovenous fistula remains the best primary means of obtaining hemodialysis access. When this is unavailable, a prosthetic conduit must be considered. Selection of the appropriate access site has become increasingly important because of the increasing long-term survival of hemodialysis patients. A strategy is presented for sequential graft placement once revision at a given site is no longer feasible, with emphasis on efficient use of native arterial and venous structures, maximizing long-term patency, and preventing potential infectious and ischemic complications.

Thromboxane synthetase inhibition decreases polymorphonuclear leukocyte activation following hindlimb ischemia.

Ischemia of the lower extremity has been shown to cause pulmonary leukostasis and increased pulmonary artery pressure. Thromboxane (TX) has been implicated as a mediator in this process. The effect of OKY-046, a TX synthetase inhibitor, on polymorphonuclear leukocyte (PMN) production of superoxide anion (O2-) as determined by ferricytochrome reduction was examined. Fourteen dogs were subjected to 6 hours of bilateral gracilis muscle ischemia followed by 1 hour of reperfusion. O2- production from resting PMNs and PMNs stimulated with opsonized zymosan (OZ, 0.1 mg/ml) was measured prior to ischemia or drug treatment (baseline), and following reperfusion in both treated (n = 7) and control groups (n = 7). Serum TX levels were measured using a radioimmunoassay. Following reperfusion, TX levels in the treated group were decreased as compared with the control group (18 +/- 2 pg/ml vs. 72 +/- 26 pg/ml, P less than 0.05). Superoxide production by both resting and stimulated PMNs was also decreased in the treated group; from 0.98 +/- 0.16 nmol to 0.43 +/- 0.12 nmol O2- in the resting state (P less than 0.05) and from 13.3 +/- 1.5 nmol to 9.0 +/- 1.1 nmol O2- after stimulation (P less than 0.005). O2- production was increased in the control group following reperfusion as compared with baseline samples, and this increase was attenuated by treatment with OKY-046. TX synthetase inhibition decreases activation of PMNs following hindlimb ischemia.

The effects of nimodipine on ischemic injury of the spinal cord during thoracic aortic cross-clamping.

BACKGROUND: The purpose of this study was to evaluate the protective effects of a neuroselective calcium antagonist, nimodipine on spinal cord ischemia during and after thoracic aortic cross-clamping. METHODS: Thirty adult dogs underwent 60 minutes of thoracic aortic cross-clamping via a left thoracotomy. The dogs were randomized into 3 groups (n = 10) and received either intravenous control (normal saline), sham (polyethylene glycol) or nimodipine solution during a period of 150 minutes. Spinal cord perfusion (SCP) was directly monitored using a laser doppler flowmeter. After 48 hours, neurologic status was assessed using Tarlov scores and the spinal cords evaluated histologically for evidence of ischemia (grades 1-4: severe to mild ischemia). RESULTS: Twenty-six dogs survived the operation. Proximal (carotid) blood pressure increased 30-40% and cerebrospinal fluid (CSF) pressure increased 50% during cross-clamping for all 3 groups. The SCP decreased predictably during cross-clamping in all dogs but after unclamping, the nimodipine group had significantly less hyperperfusion than the saline and sham control groups (30 min after unclamping, control: 74.1 +/- 12.6 ml/min, sham: 51.8 +/- 4.15 ml/min, nimodipine: 33.1 +/- 3.9 ml/min, p = 0.04). This hyperperfusion phenomenon correlated with adverse neurologic (Tarlov score) outcome (p = 0.01). Paraplegia rates were 78% (control), 70% (sham) and 71% (nimodipine) (p = NS). The histologic grades of the spinal cords from those dogs which received nimodipine tended to correspond to better tissue preservation (control: 1.72 +/- 0.49, sham: 1.75 +/- 0.46, nimodipine: 2.14 +/- 0.56, p = NS). CONCLUSIONS: Nimodipine used as single agent therapy failed to show a statistically significant clinical neurologic benefit. However, nimodipine significantly decreased postischemic reperfusion hyperemia in the spinal cord as measured by laser doppler flowmetry. This reduced hyperperfusion, which significantly correlated with functional outcome, may be responsible for dampening neural cell damage. Thus, nimodipine should be considered as an adjunct to a multimodality approach in the prevention of spinal cord ischemia during thoracic and thoracoabdominal aortic reconstructions.

Noninvasive evaluation of the lymphatic system with lymphoscintigraphy: a prospective, semiquantitative analysis in 386 extremities.

PURPOSE: Lymphoscintigraphy has emerged as the diagnostic test of choice in patients with suspected lymphedema. To assess the lymphatic circulation of 386 extremities in 188 patients, we prospectively recorded a semiquantitative index of lymphatic transport in addition to visual evaluation of lymphoscintigraphy image patterns. METHODS: Sixty-one male and 127 female patients were studied (mean age 48 years, range 13 to 87 years). Twenty had upper extremity swelling, and 168 had lower extremity swelling. The disease was bilateral in 60 patients. Lymphoscintigraphy was performed by injecting a mean of 503 microCi of technetium 99m-antimony trisulfide colloid subcutaneously into the second interdigital space of the extremity. Time for transport to regional lymph nodes, appearance of lymph vessels and nodes and distribution pattern were scored. These scores were compiled into a modified Kleinhans transport index (TI). To assess the venous circulation, 155 patients underwent evaluation of the venous system by impedance plethysmography, ultrasonography, or contrast venography. RESULTS: The mean TI (+/- SEM) in 79 asymptomatic extremities was 2.6 +/- 0.5, with 66 (83.5%) demonstrating normal lymphoscintigraphy pattern (TI < 5). Patients with clinical diagnosis of lymphedema (n = 124) had a mean TI of 23.8 +/- 1.5; 81.5% of these were greater than 5. Fifty-six patients (30%) had primary and 68 (36%) had secondary lymphedema. (TI of 26 +/- 3.5 and 22.1 +/- 1.9, respectively, p = NS). Patients without any lymphatic transport (TI of 45) were more likely to have cellulitis in their history (p < 0.05). Contrast lymphangiography in six patients correlated with lymphoscintigraphy. Sixty-four patients (34%) had swelling without lymphedema (venous edema, cardiac edema, lipedema, etc.; TI of 1.9 +/- 0.4, p < 0.001). Of the 41 patients with abnormal venous studies, 18 (44%) had an elevated TI. CONCLUSIONS: Semiquantitative evaluation of the lymphatic transport with lymphoscintigraphy reliably depicts abnormalities in the lymphatic circulation. Lymphoscintigraphy excluded lymphedema as a cause of leg swelling in one third of our patients.

Chronic changes in blood flow alter endothelium-dependent responses in autogenous vein grafts in dogs.

PURPOSE: Experiments were designed to determine the effects of blood flow on endothelium-dependent relaxations in canine vein grafts. METHODS: Blood flow through reversed femoral vein grafts was either increased by a distal arteriovenous fistula (increased flow), unmanipulated (normal flow), or reduced by a proximal adjustable clamp (reduced flow). Six weeks after implantation, blood flow through the graft was measured. Rings cut from grafts were suspended for the measurement of isometric force in organ chambers to determine endothelial function. RESULTS: Blood flow was significantly greater in grafts with a distal fistula compared to grafts with normal or decreased flow. Endothelium-dependent relaxations to acetylcholine were absent in all grafts. Endothelium-dependent relaxations to adenosine diphosphate, thrombin, and the calcium ionophore A23187 were less in grafts with reduced flow compared with grafts with increased flow. Relaxations to these agents in grafts with increased flow were reduced by an analog of L-arginine. Neointimal hyperplasia was increased in grafts with reduced flow. CONCLUSIONS: These data demonstrate that chronic diminution of blood flow decreases receptor-mediated release of endothelium-derived relaxing factors and increases neointimal hyperplasia in canine vein grafts. The production of endothelium-derived relaxing factors, one of which is nitric oxide, may influence the development of myointimal hyperplasia in vein grafts.

Health-related quality of life and functional outcome following arterial reconstruction for limb salvage.

Vascular surgery outcomes have traditionally been measured by limb salvage and graft patency. However, as health care resources are rationed, the patient's functional outcome and quality of life will require assessment. The in situ saphenous vein graft has proven successful in achieving long-term limb salvage for patients with critical ischemia, with the expectation of preserving a life-style and sense of well-being that would be lost with limb amputation. This study was conducted to measure functional capacity and quality of life in these patients. Seventy patients with successful in situ saphenous vein bypass grafts constructed for limb-threatening ischemia, followed for a mean of 45.6 months in a surveillance program with normal graft flow characteristics, were compared with a group of age and gender-matched controls with normal limb pressures and no history of vascular occlusive disease. A questionnaire was designed from standardized health status scales and administered to the two groups to assess symptoms, health perceptions, physical functioning and life quality. When comparing the groups of revascularized and control patients, symptoms and perceptions about their health were similar. However, the revascularized patients had significantly decreased functional capacity in their ability to walk various distances (P< or =0.005), perform household tasks (P< or =0.001) and bathe (P< or =0.001). The patient group with vascular grafts functioned as well as the controls only in activities of dressing and using the toilet. Indicators of life quality that rate independence and mobility, including the ability to procure groceries (P< or = 0.001), prepare meals (P< or =0.005) participate in social activities (P< or =0.001) and drive an automobile (P< or =0.01), were also significantly limited in the patients with successful vascular reconstructions. Although achieving long-term limb salvage and graft patency, the patients in this group of successful vascular reconstructions retain functional disabilities that require significant care. Despite these physical handicaps, these patients have a remarkably similar sense of well-being and lack of somatic complaints compared with the control group. This medical outcome study identifies the functional capacity and lifetime needs for vascular surgery patients that will provide useful data for those responsible for allocating health care resources.

Surgical technique and preliminary results of endoscopic subfascial division of perforating veins.

PURPOSE: Direct surgical ligation of incompetent perforating veins has been reported to effectively treat severe chronic venous insufficiency. It is associated, however, with significant wound complications. We evaluate our early experience with endoscopic subfascial division of the perforating veins. METHODS: From August 5, 1993, to December 31, 1994, 11 legs in nine patients (five male and for female) were treated with endoscopic subfascial division of perforating veins. Nine of the 11 legs had active or recently healed venous ulcers. Mean duration of the ulcerations was 5.6% years. Standard laparoscopic equipment with 10-mm ports was used to perform clipping and division of medial perforating veins through two small incisions made just below the knee, avoiding the area of ulcer and lipodermatosclerosis. Carbon dioxide was insufflated at a pressure of 30 mm Hg into the subfascial space to facilitate dissection, and a pneumatic thigh tourniquet was used to obtain a bloodless operating field. Concomitant removal of superficial veins was performed in eight limbs. Mean follow-up was 9.7 months (range, 2 to 13 months). RESULTS: A mean of 4.4 perforating veins (range, 2 to 7) were divided; tourniquet time averaged 58 minutes (range, 30 to 72). Wound infection of a groin incision and superficial thrombophlebitis were early complications; each occurred in one patient. In seven legs the ulcer healed or did not recur and symptoms resolved. In three legs, the ulceration improved, and in one it was unchanged. CONCLUSIONS: Endoscopic subfascial division of perforating veins seems to be a safe technique, with favorable early results obtained in a small number of patients. This preliminary experience supports further clinical trials to evaluate this technique.

The influence of arachidonic acid metabolites on leukocyte activation and skeletal muscle injury after ischemia and reperfusion.

Derivatives of arachidonic acid have been found to play a role in the reperfusion injury of various tissues. These compounds have a broad spectrum of activity, including modulation of white blood cell response to injured tissue. This study was designed to determine the effect of thromboxane and lipoxygenase derivatives on the local and systemic response to ischemia and reperfusion of skeletal muscle. Fifteen dogs were separated into three groups and subjected to gracilis muscle ischemia followed by 2 hours of reperfusion. One group served as controls, one group was treated with OKY-046 (a thromboxane synthetase inhibitor), and one group was treated with diethylcarbamazine (a lipoxygenase inhibitor). White blood cell activation as measured by superoxide anion production, and eicosanoid levels were measured both in the gracilis venous effluent and central venous circulation. These results were compared to infarct size in the gracilis muscle. OKY-046 significantly reduced thromboxane production in both the central venous (102 +/- 30 to 31 +/- 9 pg/ml, p less than 0.05) and gracilis samples (107 +/- 22 to 25 +/- 6 pg/ml, p less than 0.005). This was accompanied by a reduced white cell activation in the central venous blood (15 +/- 1 to 10 +/- 1 nmol O2-, p less than 0.05), but did not affect infarct size or white cell activation in the gracilis. Conversely, diethylcarbamazine significantly reduced both white cell activation (16 +/- 1 to 10 +/- 1 nmol O2-, p less than 0.005) and infarct size in the gracilis muscles (61.6% +/- 4.5% to 28.5% +/- 8.6%, p less than 0.01), as well as reduced systemic white blood cell activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental evaluation of bleeding complications, thrombogenicity and neointimal characteristics of prosthetic patch materials used for carotid angioplasty.

Experiments were designed to compare perioperative blood loss, early thrombogenicity and morphologic and functional characteristics of the neointima of three types of prosthetic materials used for carotid artery patch angioplasty. Bilateral carotid patch angioplasties were performed in 20 dogs, using 20 gelatin-impregnated fluoropassivated Dacron (GIF), 10 untreated knitted Dacron and 10 expanded polytetrafluoroethylene (PTFE) patches (5 cm2). Intraoperative blood loss, platelet deposition at 24 h and neointimal morphology at 6 weeks after the operation were assessed. Bioassay of the neointima was performed at 6 weeks in 16 patches. Mean (s.e.m.) blood loss was significantly less in GIF patches (14.7 (2.7) ml) compared with either PTFE (75.6 (24) ml) or untreated Dacron (64.3 (9.5)) (P < 0.005). Mean (s.e.m.) platelet deposition in GIF patches (1380 (328) platelets/cm2) was approximately 50% less at 24 h than in untreated Dacron (2562 (1035) platelets/cm2) or PTFE (2140 (998( platelets/cm2) patches (P < 0.05). Neointimal coverage was greater in PTFE (94 (1.3%)) compared with GIF (79 (2.7%)) or untreated Dacron (86 (2.4%)) patches (P < 0.05). The thickness of the neointimal layer of PTFE (0.5 (0.01) mm) patches was greater than other patch types; GIF (0.2 (0.01) mm) or untreated Dacron (0.3 (0.01) mm) (P < 0.50). Under bioassay conditions, acetylcholine caused release of vasoactive relaxing factor(s) from all patches. However, relaxations from baseline were less with GIF patches (-37.9 (11.7)% versus -54.5(9.6( for untreated Dacron; -50.2 (15.2)% for PTFE) (P = n.s.). Endothelin-1 release occurred from all patches and was increased with the extent of neointimal coverage. These data demonstrate that GIF patches caused the least perioperative bleeding, were the least thrombogenic at 24 h and developed the thinnest neointima at 6 weeks. All patch materials developed a functioning neointima.

Ongoing vascular laboratory surveillance is essential to maximize long-term in situ saphenous vein bypass patency.

PURPOSE: The purpose of this study was to assess the contribution of ongoing graft surveillance to maximize long-term patency of lower limb in situ saphenous vein bypasses. METHODS: From January 1981 to October 1994, 556 autogenous grafts were constructed in 499 patients. The distal anastomosis was at the popliteal level in 207 (37%) and the tibial level in 349 (63%). All patients were enrolled in a prospective surveillance protocol to identify lesions that compromise graft patency and were evaluated at 1 day, 1 week, 6 weeks, and 3 months. Surveillance studies were then obtained every 3 months for the first 2 postoperative years and every 6 months thereafter. RESULTS: Four-hundred-fifty abnormalities were detected in 236 grafts. The median interval from the initial procedure to detection of an abnormality was 12 months (range 0 to 113 months) and varied with the location of the defect. Later in the life of the graft, progression of atherosclerotic disease manifested as inflow obstruction at a median of 15 months, and outflow disease threatened the graft at a median of 29 months (r = 0.0003). Of the 450 surveillance abnormalities, 294 (65%) occurred within the first 2 years after operation, and 156 (35%) developed more than 2 years after operation. Of the 236 grafts that developed surveillance abnormalities, 50 (21%) developed the initial defect more than 2 years after the initial bypass procedure. Eleven percent of grafts remaining free of abnormality after 2 years went on to fail. Sixty-seven interventions were performed on 62 extremities after 24 months, with 30 involving previously unrevised grafts. CONCLUSIONS: Because lesions amenable to revision continue to develop years after vein bypass construction, perpetual surveillance is required to ensure optimal rates of graft patency.

An outcome analysis of carotid endarterectomy: the incidence and natural history of recurrent stenosis.

PURPOSE: This report identifies the incidence of recurrent carotid stenosis after carotid endarterectomy (CEA) and records the natural history of the disease process to gain further insight into its proper management. METHODS: A prospective surveillance protocol with duplex imaging and velocity spectral analysis was used to detect recurrent stenosis ( > 50% diameter reduction) and to document the clinical outcomes of patients who underwent CEA. Between 1984 and 1993, 619 consecutive CEAs were performed in 587 patients. RESULTS: Recurrent carotid stenosis developed in 48 CEA sites (7.8%) during a mean follow-up interval of 34 months (range, 2 to 118 months). Normal results on intraoperative assessment correlated with a 5.6% incidence of recurrent stenosis, compared with a 19% incidence when a residual hemodynamic abnormality was present (p < 0.0003). In the first year after surgery, there were no transient ischemic attacks, strokes, or carotid occlusions from recurrent stenosis, compared with a 27% morbidity rate in later follow-up (p < 0.01). Three patients with recurrent stenosis subsequently had occlusion at the CEA site, two of whom had severe ipsilateral strokes. CONCLUSIONS: The incidence of recurrent carotid stenosis is low. Patients are at significant risk for neurologic morbidity when a recurrent stenosis occludes. With a 0.3% incidence of late stroke resulting from carotid bifurcation disease, these data confirm that CEA does provide long-term protection from stroke.

Leukocyte activation in ischemia-reperfusion injury of skeletal muscle.

Polymorphonuclear leukocyte (PMN) participation in the pathophysiology of the reperfusion injury following skeletal muscle ischemia has become recognized. We measured the activation of PMNs as evidenced by production of superoxide anion (O2-) in the isolated canine gracilis muscle preparation of ischemia-reperfusion injury. PMNs were isolated from the gracilis muscle venous effluent and central venous blood after 6 hr of bilateral gracilis ischemia and 1 hr of reperfusion in five dogs. Baseline samples were obtained prior to ischemia from the central venous circulation. Liberation of O2- from PMNs and from PMNs stimulated by opsonized zymosan was determined by measuring ferricytochrome reduction. Results are expressed as nanomoles of O2- produced/2 x 10(6) PMN +/- SEM. O2- production by unstimulated cells was increased from 0.33 +/- 0.15 nmole in the baseline samples to 0.96 +/- 0.08 nmole in the central venous sample (P less than 0.01). With stimulation by zymosan, production increased from 10.3 +/- 1.4 nmole in the baseline samples to 15.2 +/- 1.1 nmole in the central venous sample (P less than 0.05) and to 15.5 +/- 0.9 nmole in the gracilis venous sample (P less than 0.01). These increases in superoxide production were not seen in the three sham-operated animals. Mean infarct size determined by planimetry was 55%. O2- produced by PMNs from central venous blood correlated with infarct size (r = 0.934, P = 0.02). These data imply that PMNs are activated by muscular ischemia, and the degree of activation is directly related to the extent of the muscle infarction.

Production of endothelium-derived factors from sodded expanded polytetrafluoroethylene grafts.

PURPOSE: Experiments were designed to determine whether endothelium isolated from adipose tissue and sodded onto expanded polytetrafluoroethylene grafts release endothelium-derived vasoactive factors. METHODS: Thin-walled expanded polytetrafluoroethylene grafts (6 mm internal diameter, 6 cm length, 30 microm pore size), one sodded with autogenous endothelial cells, the other unsodded, were implanted bilaterally in carotid arteries of 30 male mongrel dogs. Dogs were treated with 325 mg aspirin daily. After 6 weeks grafts were excised and perfused in a bioassay system. Effluent from the grafts stimulated with either acetylcholine, thrombin, adenosine 5-diphosphate, or the calcium ionophore A23187 was superfused over rings of canine femoral arteries without endothelium contracted with phenylephrine. Effluent from the grafts was analyzed by radioimmunoassay for thromboxane B2, 6-keto-prostaglandin F1alpha, endothelin-1, and C-type natriuretic peptide. RESULTS: Ninety percent of the sodded grafts and 87% of the unsodded grafts were patent after 6 weeks. Bioassay rings superfused with effluent from sodded grafts stimulated with acetylcholine relaxed significantly more than rings superfused with effluent from similarly stimulated unsodded grafts. Biochemical analysis of the effluent showed an increase in 6-keto prostaglandin F1alpha and C-type natriuretic peptide and a decrease in endothelin-1 and thromboxane B2 release from the sodded compared with the unsodded grafts. Scanning electron microscopy showed a continuous layer of endothelial cells lining only the sodded grafts. Staining for alpha-actin and heavy-chain myosin showed a differentiated layer of smooth muscle below the endothelial layer on the sodded grafts. Finally, there was positive staining for C-type natriuretic peptide and endothelin-1 in the endothelium of the sodded grafts. CONCLUSIONS: These results indicate that endothelial cells of sodded expanded polytetrafluoroethylene grafts produce endothelium-derived vasoactive factors. In addition, receptor-coupled synthesis/release of these factors is retained in sodded endothelial cells.

Ascorbic acid prevents cigarette smoke injury to endothelium-dependent arterial relaxation.

BACKGROUND: Arterial endothelium-dependent acetylcholine relaxation is impaired by smoking, and this injury may be mediated by oxygen free radicals. The purpose of this study was to examine the effect of ascorbic acid (AA) treatment on this injury. MATERIALS AND METHODS: New Zealand White rabbits (n = 6, each group) were placed in a 240-ft3 airflow chamber for 3 h per day, 5 days per week over an 8-week period. Animals were divided into four groups and fed rabbit chow and water or rabbit chow and AA (250 ml/kg)-supplemented water. The control-smoke rabbit group and the ascorbic acid-smoke rabbit group were exposed to mainstream cigarette smoke from a robotic smoke generator for the 3-h period, while the control-no smoke rabbit group and ascorbic acid-no smoke rabbit group were similarly placed in the chamber without smoke. At the end of 8 weeks, rabbits were sacrificed and segments of their superficial femoral arteries were suspended from tension transducers and the maximal contraction was determined. The remaining rings were contracted to 50% of the maximum and relaxation was determined by adding acetylcholine. Groups were compared using one-way ANOVA. RESULTS: Rings from control-smoke (5.13 +/- 0.21 g) and AA-smoke rabbits (6. 24 +/- 0.46 g) exhibited increased mean contraction to KCl (P < 0. 05) compared to control-no smoke rabbits (3.86 +/- 0.40 g). Acetylcholine-dependent relaxation was significantly reduced in the rings from the control-smoke rabbits compared to control-no smoke rabbits (acetylcholine, 5 x 10(-7) M: 24.7 +/- 2.7% versus 55.3 +/- 8.0%; acetylcholine, 7 x 10(-7) M: 27.5 +/- 2.3% versus 56.3 +/- 9. 2%). The AA-smoke group (acetylcholine, 5 x 10(-7) M: 61.8 +/- 12. 4%; 7 x 10(-7) M: 67.9 +/- 11.4%) had significantly increased relaxation compared to the control-smoke group (P < 0.05). There was no statistical difference in the mean percentage ring relaxation between the control-no smoke, AA-no smoke, and AA-smoke groups. CONCLUSIONS: Ascorbic acid protected the artery from cigarette smoke-induced endothelial injury.