Impact of aortoiliac tortuosity on endovascular repair of abdominal aortic aneurysms: evaluation of 3D computer-based assessment.

OBJECTIVE: The purpose of this study was to examine the effect of aortoiliac tortuosity, as assessed by observers and 3-dimensional (3D) computer-based methods, on the conduct and outcome of endovascular repair of abdominal aortic aneurysms. METHODS: Infrarenal aortoiliac tortuosity was measured in 75 patients (mean follow-up, 14.8 +/- 10.4 months) who underwent endovascular repair of abdominal aortic aneurysms by using the following four methods: (1) grading by 2 experienced observers; (2) tortuosity index measured as the inverse radius of curvature (cm(-1)) at 1-mm intervals along the median luminal centerline (MLC) on 3D reconstructions of computed tomography (CT) angiograms and was calculated as the sum of values greater than 0.3 cm(-1); (3) MLC-straight line length ratio from renal to hypogastric arteries; (4) manual measurement of angles at points of angulation on anteroposterior and lateral projections of 3D CT reconstructions. In evaluating association between these measures, correlation between human observers was accepted as the gold standard. RESULTS: For rating of overall aortoiliac tortuosity, interobserver correlation (r = 0.67) was comparable with correlation of observers with tortuosity index (r = 0.67 and 0.56), whereas correlations of each observer with MLC-straight line ratio (r = 0.50 and 0.56) and cumulative angulation (r = 0.44 and 0.44) were significant but weaker. For determining the relative tortuosity of right and left aortoiliac access, agreement between observers and tortuosity index (54% and 58%; P < .05; kappa, 0.33 and 0.38) was not as good as between observers (68%; P < .001; kappa, 0.53). This difference was primarily related to evaluation of the aorta, where interobserver correlation (r = 0.71) was better than that between each observer and tortuosity index (r = 0.47 and 0.55), whereas correlations in the iliac arteries were comparable (r = 0.64 and 0.67) (all coefficients P < .01). Increased tortuosity was associated with a more complex endovascular repair, as reflected by longer fluoroscopy time (P = .05), use of more contrast material (P = .03), use of extender modules (P = .04), and more frequent use of arterial reconstruction (P = .01), but was not associated with a higher overall complication rate. Increased tortuosity, when it occurred in the aortic neck, was associated with predischarge endoleak (P = .03) but not with late endoleak, intervention, or aneurysm-related adverse events. CONCLUSION: Aortoiliac tortuosity is associated with increased complexity of endovascular aneurysm repair and with predischarge endoleak but does not appear to affect intermediate-term results. Computer-based 3D measurement of aortoiliac tortuosity is feasible and clinically meaningful. Its ultimate role in relation to human assessment must be further defined in future studies.

Ultrasound-guided thrombin injection for the treatment of iatrogenic pseudoaneurysm of the femoral artery.

BACKGROUND: Pseudoaneurysm occurring after catheterization of the femoral artery is associated with significant morbidity. Percutaneous ultrasound-guided thrombin injection has recently emerged as a potential first-line therapy. OBJECTIVES: To evaluate the efficacy of this treatment in eight patients with iatrogenic femoral artery pseudoaneurysm. METHODS: After attempted treatment with external compression had failed, eight patients with iatrogenic femoral artery pseudoaneurysm were treated with thrombin injection. Treatment performed between 2 and 9 days following arterial puncture. The study group comprised seven males and one female ranging in age from 23 to 89 years (median 70). Seven had undergone cardiac catheterization with or without intervention, and five were receiving antiplatelet and/or anticoagulant drugs. Arterial pseudoaneurysm resulted from femoral vein catheterization in one patient. Using a sterile technique and real-time Doppler ultrasound guidance, a dilute solution of bovine thrombin (average dose 250 units, range 100-600), was slowly injected directly into the pseudoaneurysm until cessation of flow was seen. Patients were allowed to walk within 2 hours of the procedure and were followed up clinically and by color Doppler ultrasound during the admission. RESULTS: Cardiac catheterization had been inadvertently performed via the superficial or profunda femoris arteries in four of the eight patients. Thrombin injection was initially successful in all eight patients without complication. Thrombosis occurred immediately in every case. Early recanalization of pseudoaneurysm occurred in one patient despite repeat thrombin injection and attempted ultrasound-guided compression. He eventually required surgical repair. The final success rate was 87.5% (7/8). CONCLUSION: Faulty puncture technique is an important risk factor for the development of post-catheterization femoral artery pseudoaneurysm. Ultrasound-guided thrombin injection is a safe, rapid, well-tolerated, inexpensive and successful therapy. If initial external compression with a sandbag fails to result in thrombosis of the pseudoaneurysm then thrombin injection should be considered as first-line therapy. If unsuccessful, it does not preclude the use of alternative treatment modalities. Further study is necessary to assess the long-term effects of thrombin injection.

Outcome after unilateral hypogastric artery occlusion during endovascular aneurysm repair.

PURPOSE: The purpose of this study was to determine the long-term functional outcome after unilateral hypogastric artery occlusion during endovascular stent graft repair of aortoiliac aneurysms. METHODS: During a 41-month period, 157 consecutive patients underwent elective endovascular stent graft repair of aortoiliac aneurysms with the Medtronic AneuRx device. Postoperative computed tomography scans were compared with preoperative scans to identify new hypogastric artery occlusions. Twenty-three (15%) patients had unilateral hypogastric occlusion, and there were no cases of bilateral occlusions. Telephone interviews about past and current levels of activity and symptoms were conducted, and pertinent medical records were reviewed. All 23 (100%) patients were available for the telephone interview. A disability score (DS) was quantitatively graded on a discrete scale ranging from 0 to 10 corresponding to "virtually bed-bound" to "greater-than-a-mile" exercise tolerance. Worsening or improvement of symptoms was expressed as a difference in DS between two time points (-, worsening/+, improving). RESULTS: Among the 23 patients, two groups were identified: 10 patients (43%) had planned and 13 patients (57%) had unplanned or inadvertent occlusions. The patients in the two groups did not differ significantly in the mean age (73.4 vs 73.7 years), sex (male:female, 9:1 vs 10:3), and duration of follow-up (15.6 vs 14.4 months). Nine (39%) of the 23 patients, five patients in the planned and four patients in the unplanned group, reported significant symptoms of hip and buttock claudication ipsilateral to their occluded hypogastric arteries. The mean decrement from baseline of these nine patients in their DS postoperatively was -3.3. The symptoms were universally noted on postoperative day 1. Although most patients improved (89%), one (11%) never got better. Among those whose symptoms improved, the mean time to improvement was 15 weeks, but with a plateau thereafter resulting in a net decrement of DS of -2.3 from baseline. Finally, when questioned whether they would undergo the procedure again, all 23 patients unanimously answered, "Yes." CONCLUSIONS: A significant number (39%) of patients who sustain hypogastric artery occlusion after endovascular aneurysm repair have symptoms. Although most patients with symptoms have some improvement, none return to their baseline level of activity. Despite this, all patients in retrospect would again choose endovascular repair over conventional open repair.

Preoperative dipyridamole-thallium scanning, selective coronary revascularization and long-term survival in patients with critical lower limb ischemia.

BACKGROUND: A large proportion of patients with critical limb ischemia have advanced, often asymptomatic coronary artery disease which is associated with increased perioperative risk and decreased long-term survival. METHODS: We evaluated retrospectively the short and long-term effect of routine dipyridamole-thallium cardiac scanning (DTS) and selective coronary revascularization in 113 consecutive patients who were scheduled for revascularization of the lower extremity. RESULTS: DTS was abnormal in 60 (53.1%) patients and demonstrated a moderate-severe reversible defect in 26 (23.0%) patients. On the basis of DTS and clinical evaluation 33 (29.2%) patients were referred for coronary catheterization. Of these, 9 underwent PTCA and 4 underwent coronary artery bypass, without complications. Surgical revascularization of the limbs was performed in all but two patients. Two (1.8%) patients died postoperatively, three (2.7%) sustained nonfatal postoperative myocardial infarctions. None of the patients who underwent preoperative coronary revascularization suffered a cardiac complication after the peripheral vascular operation. During mean follow-up of 31.7 months, 30 (28.0%) patients died. A moderate-severe reversible defect on DTS was the strongest predictor for shortened survival (Exp(b)=0.61, CI 95%=0.42-0.88; p=0.006). Patients who underwent preoperative coronary revascularization followed a survival curve approaching those without a reversible defect on DTS (mean survival 61+/-8 vs 63+/-4 months; NS) which was significantly better than those with such a defect who did not undergo coronary revascularization (mean survival 34+/-5 months; p=0.03). CONCLUSIONS: While the perioperative benefits of routine preoperative DTS screening in patients with critical limb ischemia, remain debatable, it provides an opportunity for identification and treatment of life-limiting coronary artery disease and improving survival.

Eccentric stent graft compression: an indicator of insecure proximal fixation of aortic stent graft.

PURPOSE: The purpose of this study was to determine whether radiographically demonstrated proximal stent graft contour can be used as a marker for security of proximal neck fixation after endovascular aneurysm repair. METHODS: Stent graft structure was examined in 100 consecutive patients with abdominal aortic aneurysms who were treated with the stent graft. Stent graft integrity, stent contour, angulation, compression, and position were assessed by use of plain abdominal radiography, and the results were correlated with contrast computed tomography (CT) scanning, clinical findings, and outcomes. Repeated imaging was carried out during follow-up of 3 to 38 (mean, 12) months. RESULTS: Stent graft repair was successful in all 100 patients. No stent fractures were identified. Concentric compression of the proximal portion of the stent graft was visible in 69% of patients and reflected deliberate oversizing of the stent graft at the time of implantation. In 5% of patients, a short eccentric compression deformity of the proximal stent was observed. This finding was associated with an increased risk of stent graft migration (P <.01) and with an increased risk for development of a late proximal (type I) endoleak (P <.01). Compared with CT scanning, abdominal radiography was less useful for assessment of short distances of migration (sensitivity 67%; specificity 79%). However, they provided better definition of the stent graft in relation to bony landmarks and better visualization of aortic calcification than CT with three-dimensional reconstruction. CONCLUSION: Plain abdominal radiographs are important in the postoperative evaluation of patients with aortic stent grafts. They allow for more precise evaluation of the structural elements of the stent graft than CT scanning and may disclose inadequate proximal fixation by demonstration of an eccentric compression deformity. They are less useful for assessment of migration.

Duplex ultrasound scanning versus computed tomographic angiography for postoperative evaluation of endovascular abdominal aortic aneurysm repair.

OBJECTIVE: The purpose of this study was to compare duplex ultrasound scanning and computed tomographic (CT) angiography for postoperative imaging and surveillance after endovascular repair of abdominal aortic aneurysm (AAA). METHODS: One hundred consecutive patients with AAA underwent endovascular (Medtronic AneuRx, stent graft) aneurysm repair and were imaged with both CT angiography and duplex ultrasound scanning at regular intervals after the procedure. Each imaging modality was evaluated for technical adequacy and for documentation of aneurysm size, endoleak, and graft patency. In concurrent scan pairs, accuracy of duplex scanning was compared with CT. RESULTS: A total of 268 CT scans and 214 duplex scans were obtained at intervals of 1 to 30 months after endovascular aneurysm repair (mean follow-up interval, 9+/-7 months). All CT scans were technically adequate, and 198 (93%) of 214 duplex scans were technically adequate for the determination of aneurysm size, presence of endoleak, and graft patency. Concurrent (within 7 days of each other) scan pairs were obtained in 166 instances in 76 patients (1-6 per patient). The maximal transverse aneurysm sac diameter measured with both methods correlated closely (r = 0.93; P <.001) without a significant difference on paired analysis. In 92% of scans, measurements were within 5 mm of each other. Diagnosis of endoleak on both examinations correlated closely (P <.001), and compared with CT, duplex scanning had a sensitivity of 81%, a specificity of 95%, a positive predictive value of 94%, and a negative predictive value of 90%. Discordant results occurred in 8% of examinations, and in none of these was the endoleak close to the attachment sites or associated with aneurysm expansion. An endoleak was demonstrated on both tests in all eight patients who had an endoleak judged severe enough to warrant arteriography. Graft patency was documented in each instance, without discrepancy, with both modalities. CONCLUSIONS: High-quality duplex ultrasound scanning is comparable to CT angiography for the assessment of aneurysm size, endoleak, and graft patency after endovascular exclusion of AAA.

High rate of candidemia in patients sustaining injuries in a bomb blast at a marketplace: a possible environmental source.

In this study, a cluster of candidemia among patients sustaining injuries in a bomb blast at a marketplace was investigated by means of a multivariate analysis, a case-control study, and quantitative air sampling. Candidemia occurred in 7 (30%) of 21 patients (58% of those admitted to the intensive care unit [ICU]) between 4 and 16 days (mean, 12 days) after the injury and was the single most frequent cause of bloodstream infections. Inhalation injury was the strongest predictor for candidemia by multivariate analysis. Candidemia among the case patients occurred at a significantly higher rate than among comparable trauma patients injured in different urban settings, including a pedestrian mall (2 of 29; P=. 02), and among contemporary ICU control patients (1 of 40; P=.001). Air sampling revealed exclusive detection of Candida species and increased mold concentration in the market in comparison with the mall environment. These findings suggest a role for an exogenous, environmental source in the development of candidemia in some trauma patients.

Will endovascular repair replace open surgery for abdominal aortic aneurysm repair?

OBJECTIVE: To evaluate of the impact of endovascular aneurysm repair on the rate of open surgical repair and on the overall treatment of abdominal aortic aneurysms (AAAs). METHODS: All patients with AAA who were treated during two consecutive 40-month periods were reviewed. During the first period, only open surgical repair was performed; during the subsequent 40 months, endovascular repair and open surgical repair were treatment options. RESULTS: A total of 727 patients with AAA were treated during the entire period. During the initial 40 months, 268 patients were treated with open surgical repair, including 216 infrarenal (81%), 43 complex (16%), and 9 ruptured (3%) aortic aneurysms. During the subsequent 40 months, 459 patients with AAA were treated (71% increase). There was no significant change in the number of patients undergoing open surgical repair and no significant difference in the rate of infrarenal (238 [77%]) and complex (51 [16%]) repairs. A total of 353 patients were referred for endovascular repair. Of these, 190 (54%) were considered candidates for endovascular repair based on computed tomography or arteriographic morphologic criteria. Analyzing a subgroup of 123 patients, the most common primary reasons for ineligibility for endovascular repair were related to morphology of the neck in 80 patients (65%) and of the iliac arteries in 35 patients (28%). A total of 149 patients underwent endovascular repair. Of these, the procedure was successful in 147 (99%), and 2 (1%) patients underwent surgical conversion. The hospital death rate was 0%, and the 30-day death rate was 1%. During a follow-up period of 1 to 39 months (mean 12 +/- 9), 21 secondary procedures to treat endoleak (20) or to maintain graft limb patency (1) were performed in 17 patients (11%). There were no aneurysm ruptures or aneurysm-related deaths. CONCLUSIONS: Endovascular repair appears to have augmented treatment options rather than replaced open surgical repair for patients with AAA. Patients who previously were not candidates for repair because of medical comorbidity may now be safely treated with endovascular repair.

Endovascular repair of abdominal aortic aneurysms: eligibility rate and impact on the rate of open repair.

OBJECTIVE: The purpose of this study was to determine the rate of eligibility among patients with abdominal aortic aneurysms (AAAs) considered for endovascular repair and to examine the effect of an endovascular program on the institutional pattern of AAA repair. METHODS: All patients evaluated for endovascular AAA repair since the inception of an endovascular program were reviewed for determination of eligibility rates and eventual treatment. Open AAA repairs were categorized as simple (uncomplicated infrarenal), complex (juxtarenal, suprarenal, thoracoabdominal, infected), or ruptured, and their rates before and after initiation of an endovascular program were compared. RESULTS: Over 3 years, 324 patients were considered for endovascular AAA repair; 176 (54%) were candidates, 138 (43%) were not candidates, and 10 (3%) did not complete the evaluation. The rate of eligibility increased significantly from 45% (66/148 patients) during the first half of this period to 63% (110/176 patients) during the second half (P <. 001). Candidates were significantly younger (74.4 +/- 7.6 years) than noncandidates (78.3 +/- 6.7 years) (P <.01), and their aneurysm diameter tended to be smaller (57.6 +/- 9.2 mm compared with 60.8 +/- 12.3 mm; P =.06). The most common reason for ineligibility was an inadequate proximal aortic neck. Of 176 candidates, 78% underwent endovascular repair, and 6% underwent open repair. Of 138 noncandidates, 56% underwent surgical repair. Over a period of 6 years, 542 patients with AAAs (429 simple, 86 complex, 27 ruptured) underwent open repair. The total number and ratio of simple to complex open repairs for nonruptured aneurysms during the 3 years before the initiation of the endovascular program (213 simple, 44 complex) were not significantly different from the repairs over the subsequent 3-year period (216 simple, 42 complex). Similarly, no difference in the total number and the ratio of simple to complex open repairs was found between the first and the second 18-month periods since the initiation of the endovascular program. CONCLUSIONS: The rate of eligibility of patients with AAA for endovascular repair appears to be higher than previously reported. The presence of an active endovascular program has not decreased the number or shifted the distribution of open AAA repair.

Rate of change in abdominal aortic aneurysm diameter after endovascular repair.

OBJECTIVE: Untreated abdominal aortic aneurysms (AAAs) enlarge at a mean rate of 3.9 mm/y with great individual variability. We sought to determine the effect of endovascular repair on the rate of change in aneurysm size. METHODS: There were 110 patients who underwent endovascular AAA repair at Stanford University Medical Center and who were followed up for 1 to 30 months (mean, 10 months) with serial contrast-infused helical computed tomography (CT). Maximal aneurysm diameter was determined using two independent methods: (1) measured manually, from cross-sectional computed tomography (XSCT) angiograms and (2) calculated from quantitative three-dimensional computed tomography (3DCT) data as orthonormal diameter. RESULTS: Maximal cross-sectional aneurysm diameter measured by hand (XSCT) and calculated as orthonormal values (3DCT) correlated closely (r = 0.915; P <.001). The XSCT-measured diameter was larger by 2.3 +/- 3. 75 mm (P <.001), and the 95% CI for SE of the bias was 1.85 to 2.75 mm. Preoperative aneurysm diameter (XSCT 59.1 +/- 8.4 mm; 3DCT 58.1 +/- 9.3 mm) did not differ significantly from the initial postoperative diameter. Considering all patients, XSCT diameter decreased at a rate of 0.34 +/- 0.69 mm/mo, and 3DCT diameter decreased at a rate of 0.28 +/- 0.79 mm/mo. Aneurysms in patients without endoleaks had a higher rate of decrease, an XSCT diameter by 0.50 +/- 0.74 mm/mo, and 3DCT diameter by 0.46 +/- 0.84 mm/mo. In these patients, mean absolute decrease in diameter at 6 months was 3. 4 +/- 4.5 mm (XSCT) and 3.3 +/- 5.9 mm (3DCT) and at 12 months, 5.9 +/- 5.7 mm (XSCT) and 5.4 +/- 5.7 mm (3DCT). Aneurysms in patients with persistent endoleaks did not change in mean XSCT diameter, and 3DCT diameter increased by 0.12 +/- 0.52 mm/mo (not significant). Aneurysm diameter remained within 4 mm of original size in 68% (3DCT) to 71% (XSCT) of patients. In one patient, aneurysm diameter increased (XSCT and 3DCT) more than 5 mm. Four patients who had a new onset endoleak had a much higher expansion rate than those with a chronic endoleak (P <.05). CONCLUSIONS: The rate of decrease in aneurysm size (annualized 3.4-4.1 mm/y) after endovascular repair of AAA approximates the reported expansion rate in untreated aneurysms. However, individual aneurysm behavior is unpredictable, and the presence of an endoleak is unreliable in predicting changes in diameter. New onset endoleaks are associated with an enlargement rate greater than that of untreated aneurysms.

Does complete aneurysm exclusion ensure long-term success after endovascular repair?

PURPOSE: To examine whether complete aneurysm exclusion is a reliable marker for successful long-term endovascular abdominal aortic aneurysm (AAA) repair. METHODS: The medical records, computed tomographic (CT) scans, and duplex examinations of all the patients who underwent endovascular AAA repair at a single institution and had at least 12 months of follow-up were reviewed. Sixty-seven patients (58 men; mean age 74 years, range 57-87) were identified. Complete aneurysm exclusion was defined by the absence of an endoleak at any time before an adverse event. The primary endpoint included all major adverse events that occurred during the postoperative period, including aneurysm expansion, acute symptoms referable to the AAA, late secondary procedures, ruptures, and deaths from ruptures and all other causes. RESULTS: There were 44 adverse events (8 expanding aneurysms, 4 acute symptoms, 17 secondary procedures, and 15 deaths from other causes) in 28 (42%) patients. Among 36 (54%) patients who had initial complete aneurysm exclusion (no endoleak), 12 (33%) experienced adverse events, compared with 16 (52%) events in 31 patients who had endoleak (chi2 = 1.59, p = 0.21). CONCLUSIONS: There was no statistically significant difference in adverse events based on the presence or absence of endoleak. Complete aneurysm exclusion as defined by absence of an endoleak does not indicate an event-free postoperative course. A better marker of clinical success of endovascular AAA repair is needed.

Results of reconstruction in major pelvic and extremity venous injuries.

PURPOSE: Outcome and venous patency after reconstruction in major pelvic and extremity venous injuries was studied. METHODS: We retrospectively reviewed 46 patients with 47 venous injuries. RESULTS: Injuries were caused by penetrating trauma in 37 extremities, blunt trauma in 6 patients, and were iatrogenic in 4 patients. Pelvic veins were injured in 4 patients, lower-extremity veins were injured in 39 limbs in 38 patients, and upper-extremity veins were injured in 4 patients. Concomitant arterial injuries occurred in 37 patients. Venous repairs were mostly of the complex type and included spiral or panel grafts in 15 (32%) reconstructions, interposition grafts or patch venoplasty in 19 (40%) reconstructions, end-to-end and lateral repair in 11 patients, and ligation in 2 patients. Two patients underwent early amputation. Early transient limb edema occurred in 2 patients, and postoperative venous occlusions were documented in 4 patients. Full function was regained in 39 (81%) extremities. No variable, including 4 retrospectively applied extremity injury scores (mangled extremity severity score [MESS], limb salvage index [LSI], mangled extremity syndrome index [MESI], predictive salvage index [PSI]), correlated with outcome. High values on all 4 scores were significantly associated with reexplorations (P <.02), which were done in 8 patients for debridement (5), arrest of bleeding (2), and repair of a missed arterial injury (1). Follow-up of 28 +/- 6 months on 27 patients (57%; duplex scan in 18, continuous-wave Doppler and plethysmography in 9, and venography in 3) showed 1 occlusion 6 weeks after the injury and patency of all other venous reconstructions. CONCLUSION: Reconstructions of major venous injuries with a high rate of complex repairs result in a large proportion of fully functional limbs and a high patency rate. A high extremity injury score predicts the need for reexploration of the extremity. Mostocclusions occur within weeks of injury, and the subsequent delayed occlusion rate is very low.

Mesenteric bypass for chronic mesenteric ischaemia.

Chronic mesenteric ischaemia is an uncommon disease that requires treatment to relieve the symptoms of abdominal angina and to prevent intestinal infarction. Over a period of 3 years, 12 patients with visceral artery stenosis or occlusion were referred to the authors' service and 10 underwent mesenteric bypass grafting. Both the coeliac and the superior mesenteric arteries were revascularized in four patients, and the superior mesenteric artery alone in six patients, using a variety of grafts and graft configurations. This was done in conjunction with aortic graft placement in four cases and with renal bypass in three. All patients survived the procedure. At a mean follow-up of 28 months, one patient died of myocardial infarction 42 months after surgery, while all survivors are symptom-free. Chronic mesenteric ischaemia can be treated safely and effectively. The variation in the pattern of mesenteric occlusions and the frequent association with aortic and renovascular disease does not allow for a single 'best' technical solution but requires the surgical procedure to be individually tailored.

Thoracic aorta transobturator bipopliteal bypass as eventual durable reconstruction after removal of an infected aortofemoral graft.

A 36-year-old man was referred with aortofemoral graft infection and perigraft duodenal erosion. The aortofemoral graft was removed, and bilateral axillo-superficial femoral grafts were constructed. Recurrent failures of these grafts prompted us to convert to a more-durable reconstruction. A straight graft was anastomosed to the lower thoracic aorta, routed retroperitoneally, and attached to an inverted U-shaped bilateral transobturator bypass graft, which was anastomosed to both above-knee popliteal arteries. After 3 years, the patient has remained well and the grafts are patent. This operation represents a durable in-line reconstruction that avoids all previously infected areas after removal of an infected aortofemoral graft.

Vascular smooth muscle cells from injured rat aortas display elevated matrix production associated with transforming growth factor-beta activity.

The arterial response to injury is characterized by a short period of increased proliferation and migration of vascular smooth muscle cells, followed by an extended period of extracellular matrix accumulation in the intima. Transforming growth factor-beta (TGF-beta) has been implicated as a causative factor in the formation of extracellular matrix in this process, which leads to progressive thickening of the intima, known as intimal hyperplasia. In vitro analysis of vascular smooth muscle cells harvested from normal rat aortas and from aortas injured 14 days earlier showed that both types of cells attached equally well to culture dishes but that the initial spreading of the cells was increased in cells derived from injured vessels. Cells from the injured arteries produced more fibronectin and proteoglycans into the culture medium than the cells from normal arteries and contained more TGF-beta 1 mRNA. TGF-beta 1 increased proteoglycan synthesis by normal smooth muscle cells, and the presence of a neutralizing anti-TGF-beta 1 antibody reduced proteoglycan synthesis by the cells from injured arteries in culture. Fibronectin synthesis was not altered by these treatments. These results indicate that the accumulation of extracellular matrix components in neointimal lesions is at least partially caused by autocrine TGF-beta activity in vascular smooth muscle cells.