Effects of nonmagnetic interparticle forces on magnetorheological fluids.

Effects of nonmagnetic interparticle forces on the on- and off-state behavior of magnetorheological fluids are investigated experimentally and with particle-level simulations. Suspensions of iron particles in an aliphatic oil are modified by surface-active species. The modifications significantly alter the off-state properties, but have little impact on the field-induced stresses. Simulations show similar behavior. Off-state rheological properties are strongly influenced by van der Waals forces and modifications of the short-range repulsive forces. Field-induced stresses are less sensitive to the nonmagnetic forces.

Structural MRI of carotid artery atherosclerotic lesion burden and characterization of hemispheric cerebral blood flow before and after carotid endarterectomy.

Collateral circulation plays a major role in maintaining cerebral blood flow (CBF) in patients with internal carotid artery (ICA) stenosis. CBF can remain normal despite severe ICA stenosis, making the benefit of carotid endarterectomy (CEA) or stenting difficult to assess. Before and after surgery, we assessed CBF supplied through the ipsilateral (stenotic) or contralateral ICA individually with a novel hemisphere-selective arterial spin-labeling (ASL) perfusion MR technique. We further explored the relationship between CBF and ICA obstruction ratio (OR) acquired with a multislice black-blood imaging sequence. For patients with unilateral ICA stenosis (n = 19), conventional bilateral labeling did not reveal interhemispheric differences. With unilateral labeling, CBF in the middle cerebral artery (MCA) territory on the surgical side from the ipsilateral supply (53.7 +/- 3.3 ml/100 g/min) was lower than CBF in the contralateral MCA territory from the contralateral supply (58.5 +/- 2.7 ml/100 g/min), although not statistically significant (p = 0.09). The ipsilateral MCA territory received significant (p = 0.02) contralateral supply (7.0 +/- 2.7 ml/100 g/min), while ipsilateral supply to the contralateral side was not reciprocated. After surgery (n = 11), ipsilateral supply to the MCA territory increased from 57.3 +/- 5.7 to 67.3 +/- 5.4 ml/100 g/min (p = 0.03), and contralateral supply to the ipsilateral MCA territory decreased. The best predictor of increased CBF on the side of surgery was normalized presurgical ipsilateral supply (r(2) = 0.62, p = 0.004). OR was less predictive of change, although the change in normalized contralateral supply was negatively correlated with OR(excess) (=OR(ipsilateral) - OR(contralateral)) (r(2) = 0.58, p = 0.006). The results demonstrate the effect of carotid artery stenosis on blood supply to the cerebral hemispheres, as well as the relative role of collateral pathways before surgery and redistribution of blood flow through these pathways after surgery. Unilateral ASL may better predict hemodynamic surgical outcome (measured by improved perfusion) than ICA OR.

Impact of exclusion criteria on patient selection for endovascular abdominal aortic aneurysm repair.

PURPOSE: Wide-ranging predictions have been made about the usefulness of endovascular repair for patients with abdominal aortic aneurysms (AAAs). The availability of US Food and Drug Administration-approved devices has removed the restrictions on patient selection, which had been controlled by device trials. This study examined the applicability of endovascular AAA repair and identified the anatomic barriers to successful endovascular AAA repair that should guide future device development. METHODS: All patients who came to our institution for infrarenal AAA repair between April 1998 and June 2000 were offered evaluation for endovascular repair. Thin-cut spiral computed tomography scans and arteriograms were obtained on all patients, and their anatomic characteristics were prospectively entered into a database. A wide selection of available devices allowed the treatment of diverse AAA anatomic features. RESULTS: A total of 307 patients were examined (264 men, 43 women). Of these, 204 patients (66%; 185 men, 19 women) underwent endovascular repair, and 103 patients (34%, 79 men, 24 women) were rejected. Reasons for exclusion included short aneurysm neck (56, 54%), inadequate access because of small iliac arteries (48, 47%), wide aneurysm neck (41, 40%), presence of bilateral common iliac aneurysms extending to the hypogastric artery (22, 21%), excessive neck angulation (14, 14%), extensive mural thrombus in the aneurysm neck (10, 10%), extreme tortuosity of the iliac arteries (10, 10%), accessory renal arteries originating from the AAA (6, 6%), malignancy discovered during the examination (5, 5%), and death during the examination interval (2, 2%). Rejected patients had an average of 1.9 exclusion criteria (range, 1 to 4). A disproportionate number of women were excluded because of anatomic findings (P = .0009). Although 80% of patients who were at low risk for surgery qualified for endovascular repair, only 49% of our patients who were at high risk for surgery were acceptable candidates (P < .001). Of the 103 patients who were excluded, 34 (33%) underwent open surgical repair, and the remaining 69 (67%) were deemed to be unfit for open surgery. Three patients (1.4%) failed endograft placement because of inadequate vascular access. CONCLUSION: Most infrarenal AAAs (66%) can be treated with endovascular devices currently available commercially or through US Food and Drug Administration-approved clinical trials. However, patients who are at high risk for surgery and might benefit most from endovascular repair are less likely to qualify for the procedure (49%). Men (70%) are more likely than women (40%) to meet the anatomic criteria for endografting. Difficulties with vascular access and attachment site geometry predominate as reasons for exclusion. Our findings suggest that smaller profile devices, which can negotiate small and tortuous iliac arteries, are needed. Proximal and distal attachment site problems require devices that can accommodate wide and angulated attachment necks and achieve short seal zones.

Endovascular AAA repair in patients with renal insufficiency: strategies for reducing adverse renal events.

Vascular imaging, usually employing nephrotoxic contrast agents is relied upon for all aspects of endovascular AAA repair causing some to consider renal insufficiency a relative contraindication. We sought to determine if endovascular AAA evaluation and repair could be successfully accomplished by minimally or non-nephrotoxic modalities. Records and results for 98 consecutive patients undergoing endovascular AAA repair were reviewed. Patients requiring dialysis preoperatively were excluded (N=3). The average volume of iodinated contrast agent employed for intraoperative imaging was 152 cc (35-420 cc). Twenty patients (20%) had baseline renal insufficiency (serum creatinine > or =1.3 mg/dl). A rise in serum creatinine above baseline was observed in 23 (24%) patients following repair; for 15 (16%) this was permanent. Creatinine rise occurred in patients with both normal (15) and abnormal (8) baseline values (P=0.09). Rise in creatinine was independent of contrast volume employed and of the use of infrarenal vs suprarenal device fixation (P>0.05). Two (2%) patients required permanent dialysis, one of which had a normal baseline creatinine and unclear etiology for renal failure, the other had a baseline creatinine of 2 and required device placement over an accessory renal artery. Strategies to minimize the use of nephrotoxic contrast for patients with renal insufficiency included the use of MRA, rather than contrast-CT for pre and postoperative imaging (7, 35%) and use of Gadolinium rather than iodinated contrast for performance of intraoperative arteriography (5, 25%). Endovascular grafts were successfully designed and implanted based upon MRA as the sole preoperative imaging modality in every case in which it was attempted (7). Mortality was not significantly different between those with and without abnormal baseline renal function (P>0.05). Adverse events (access failures, arterial injuries, blood loss, endoleaks) were not significantly correlated with baseline renal insufficiency, rise in creatinine from baseline, use of MRA or intraoperative Gadolinium angiography (P>0.05).Pre- and postoperative evaluation and performance of endovascular AAA repair can be accomplished in patients with renal insufficiency without increasing the rate of mortality or adverse events employing a strategy which minimizes the use of nephrotoxic contrast agents, relying upon Gadolinium arteriography and MRA. Endovascular grafts can be successfully planned and followed employing MRA as the sole imaging modality.

Adenoviral mediated uteroglobin gene transfer to the adventitia reduces arterial intimal hyperplasia.

PURPOSE: The aim of this study was to investigate the feasibility of gene transfer of uteroglobin, a potent anti-inflammatory and immunomodulatory agent, via adenoviral mediated gene transfer to the adventitia in the mouse carotid ligation injury model and also to investigate the efficacy of uteroglobin in reducing neointimal hyperplasia. METHODS: Forty-five C57bl/6NHSD mice were anesthetized and left common carotid artery ligation was performed. Adenoviral vector encoding the uteroglobin gene (Ad.UG; 15 microl of 1.35 x 10(11) pfu/mL) was applied to the adventitia of the injured artery in 16 mice. In our control groups, 16 mice received adenoviral vector encoding the beta-galactosidase reporter gene (Ad.lacZ; 15 microl of 1.0 x 10(11) pfu/mL) and 13 mice received PBS only. Six mice from each group were sacrificed at 4 days for carotid artery protein extraction and Western blot analysis. The remainder were harvested at 30 days for histologic and morphometric analysis. The intima/media area ratios were calculated for each artery. The results were analyzed and compared using ANOVA and Bonferroni/Dunn post hoc testing. RESULTS: Two mice from the LacZ group and one from the PBS group died before the 30-day endpoint. Uteroglobin expression was demonstrated in the Ad.UG treated arteries by Western blot analysis. Morphometric analysis demonstrated a statistically significant reduction in the intima/media area ratio of Ad.UG treated carotids compared to controls. There was a reduction of intima/media ratio with Ad. UG treatment of 68% compared to Ad.lacZ treatment (P < 0.0001) and 62% compared to PBS treatment (P = 0.0006). There was no statistical difference between the control groups. CONCLUSION: Adenoviral mediated gene transfer via the adventitia is an effective mode of gene delivery. Adventitial uteroglobin gene transfer using an adenoviral vector induces uteroglobin protein production and significantly reduces neointimal hyperplasia in the mouse carotid ligation injury model.

Endovascular repair of aortic aneurysms: critical events and adjunctive procedures.

OBJECTIVE: We sought to define the learning curve relative to the incidence and range of intraoperative problems and to establish guidelines for troubleshooting during the endovascular repair of infrarenal aortic aneurysms. METHODS: We prospectively evaluated our first 75 consecutive cases over a 12-month period and focused on perioperative critical events and adjunctive procedures as categorical outcome measures collected during the operation. Patients were separated into three groups on the basis of the date of their operation, such that group 1 consisted of our first 25 cases, group 2 our next 25 cases, and group 3 our last 25 cases. RESULTS: At least one critical event and adjunctive procedure marked 67 (89%) of 75 cases. In 51%, there were at least two critical events and adjunctive procedures. There were no immediate open conversions or intraoperative deaths. Access problems occurred in 28% of the 75 cases and were addressed by use of brachial-femoral artery access (30%), iliac artery/aortic bifurcation balloon angioplasty (8%), and iliofemoral conduits (4%). Graft foreshortening was the most common deployment event (44%), necessitating distal covered extensions. Iliac graft limb twists and kinks occurred in 12% of cases and were managed with balloon angioplasty and uncovered stents. General incidents included balloon ruptures (10%), arterial dissections (6%), iliac artery rupture (2.6%), and lower extremity ischemia (4%). The two cases of iliac artery rupture were managed with distal covered extensions, and there were no cases of atheroemboli. Intraoperative endoleaks were encountered in 44% of the cases and included proximal attachment sites (15%), distal attachment sites (9%), type 2 sources, and "blushes." Management of intraoperative endoleaks included proximal/distal covered extensions and re-ballooning. Our 30-day endoleak rate was 20%. The incidence of critical events did not decrease in the latter one third compared with the first two thirds of cases. CONCLUSIONS: Critical events occur frequently during endovascular repair of aortic aneurysms. The intraoperative problems range from the common endoleaks, access and deployment issues, and balloon ruptures, to rare but life-threatening complications such as iliac artery rupture. A toolbox of accessories that includes wires, catheters, large balloons, covered proximal and distal extensions, and uncovered stents is essential given the frequency of adjunctive procedures. Successful aortic endografting requires more than mere familiarity with basic endovascular techniques.

The role of magnetic resonance angiography for endoprosthetic design.

OBJECTIVES: Many patients with aortic aneurysms have renal insufficiency and may be at increased risk when conventional imaging modalities (contrast-enhanced computed tomography and arteriography) are used for aortic endograft design. Our objective was to determine if magnetic resonance angiography (MRA) could be used as the sole imaging modality for endoprosthetic design. METHODS: A total of 96 consecutive patients who underwent endovascular repair of thoracic (5) and abdominal (91) aortic aneurysms (April 1998-December 1999) were included in this study. Data were collected prospectively. Gadolinium-enhanced MRA was used preoperatively in place of conventional imaging if renal insufficiency or a history of severe contrast reaction was present. The control group underwent conventional imaging. Endografts used included Ancure, AneuRx, and Talent. RESULTS: Fourteen patients (14.6%) had their endografts designed solely with MRA. Intraoperative access failure; proximal and distal extensions (unplanned); conversion to open, aborted procedures; and endoleaks occurred with equal frequency in both the MRA-designed and control groups (16.7% vs 18.3%, respectively; P =.33). Despite baseline renal insufficiency, there was no significant rise in the creatinine level after endograft implantation in patients with an MRA design (preoperative level, 1.8; postoperative level, 1.9; P =.5). CONCLUSION: MRA may be successfully used as the sole modality for aortic endograft design. The use of MRA for this purpose is noninvasive and minimizes nephrotoxic risk.

Failure of endovascular abdominal aortic aneurysm graft limbs.

OBJECTIVE: Endovascular abdominal aortic aneurysm (AAA) grafts are subject to subsequent failure of endograft limbs. We sought to determine what device-related factors could be identified that might contribute to limb failure. METHODS: We reviewed the records of patients who had undergone endovascular AAA repair and femorofemoral bypass grafting at a single institution. RESULTS: Endovascular AAA repair was performed in 173 patients. There were 137 bifurcated endografts and 36 aortomonoiliac grafts combined with femorofemoral bypass grafts, yielding a total population of 310 aortic graft limbs and 36 femorofemoral grafts. Thirty-nine additional patients underwent femorofemoral bypass grafting for occlusive disease. The cumulative primary patency of all endografts performed for AAA was 92% at 21 months. Secondary patency was achieved for all failed endograft limbs. There were 24 aortic graft limb "failures" that required intervention: seven limbs underwent thrombosis requiring revision; kinked limbs requiring stenting either at the time of graft placement (17) or subsequently (7) were identified. Fully supported endograft limbs had better primary patency (97% at 18 months) than unsupported limbs (69% at 18 months, P <.001). The aortomonoiliac grafts with femorofemoral bypass grafts tended to have better patency (97% at 18 months) than bifurcated endografts (90% at 18 months), but this did not reach statistical significance (P =.28, not significant). Femorofemoral grafts performed for occlusive disease were found to have somewhat lower patency than those performed for AAA (83% vs 92% at 18 months of follow-up, P =.37, not significant). CONCLUSIONS: Fully supported AAA endografts provide superior endograft limb patency compared with unsupported designs. Consideration should be given to routine stenting of all unsupported endograft limbs. Aortomonoiliac grafts and bifurcated grafts provide similar results for endograft limb patency. Femorofemoral bypass grafts performed in conjunction with aortomonoiliac grafts for AAA disease provide excellent short-term patency.

Gender-related differences in infrarenal aortic aneurysm morphologic features: issues relevant to Ancure and Talent endografts.

PURPOSE: The purpose of this study was to determine whether gender-related anatomic variables may reduce applicability of aortic endografting in women. METHODS: Data on all patients evaluated at our institution for endovascular repair of their abdominal aortic aneurysm were collected prospectively. Ancure (Endovascular Technologies (EVT)/Guidant Corporation, Menlo Park, Calif) and Talent (World Medical/Medtronic Corporation, Sunrise, Fla) endografts were used. Preoperative imaging included contrast-enhanced computed tomography and arteriography or magnetic resonance angiography. RESULTS: One hundred forty-one patients were evaluated (April 1998-December 1999), 19 women (13.5%) and 122 men (86.5%). Unsuitable anatomy resulted in rejection of 63.2% of the women versus only 33.6% of the men (P = .026). Maximum aneurysm diameter in women and men were similar (women, 56.94 +/- 8.23 mm; men, 59.29 +/- 13.22 mm; P = .5). The incidence of iliac artery tortuosity was similar across gender (women, 36.8%; men, 54.9%; P = .2). The narrowest diameter of the larger external iliac artery in women was significantly smaller (7.29 +/- 2.37 mm) than in men (8.62 +/- 2.07 mm; P = .02). The proximal neck length was significantly shorter in women (10.79 +/- 12.5 mm) than in men (20.47 +/- 19.5 mm; P = .02). The proximal neck width was significantly wider in women (30.5 +/- 2.4 mm) than in men (27.5 +/- 2.5 mm; P = .013). Proximal neck angulation (>60 degrees) was seen in a significantly higher proportion of women (21%) than men (3.3%; P = .012). Of the patients accepted for endografting, a significantly higher proportion of women required an iliofemoral conduit for access (women, 28.6%; men, 1.2%; P = .016). CONCLUSION: Gender-related differences in infrarenal aortic aneurysm morphologic features may preclude widespread applicability of aortic endografting in women, as seen by our experience with the Ancure and Talent devices. In addition to a significantly reduced iliac artery size, women are more likely to have a shorter, more dilated, more angulated proximal aortic neck.

Aneurysm sac pressure measurements after endovascular repair of abdominal aortic aneurysms.

OBJECTIVES: The goal of endovascular grafting of abdominal aortic aneurysms (AAAs) is to exclude the aneurysm sac from systemic pressure and thereby decrease the risk of rupture. Unlike conventional open surgery, branch vessels in the sac (eg, lumbar artery and inferior mesenteric artery [IMA]) are not ligated and can potentially transmit pressure. The purpose of our investigation was to evaluate the feasibility of various interventional techniques for measuring pressure within the aneurysm sac in patients who had undergone endovascular repair of AAAs. METHODS: Sac pressure measurements were performed in 21 patients who had undergone stent graft repair of AAAs. Seventeen of 21 patients had endoleaks demonstrated on 30-day computed tomographic (CT) scans. Access to the aneurysm sac in these patients was through direct translumbar sac puncture (5 patients), through a patent IMA accessed via the superior mesenteric artery (SMA) (9 patients), or by direct cannulation around attachment sites (3 patients). Four patients had perioperative pressure measurements obtained through catheters positioned along side of the endovascular graft at the time of its deployment. Two of these catheters were left in position for 30 hours during which time CT and conventional angiography were performed. Pressures were determined with standard arterial-line pressure transduction techniques and compared with systemic pressure in each patient. RESULTS: Elevated sac pressure was found in all patients. The sac pressure in patients with endoleaks was found to be systemic (15 patients) or near systemic (2 patients) and all had pulsatile waveforms. Elevated sac pressures were also found in patients without CT or angiographic evidence of endoleak (2 patients). Injection of the sacs in two of these patients revealed a patent lumbar artery and an IMA. CONCLUSIONS: It is possible to measure pressures from within the aneurysm sac in patients with stent grafts with a variety of techniques. Patients may continue to have pressurized AAA sacs despite endovascular AAA repair. Endoleaks transmit pulsatile pressure into the aneurysm sac regardless of the type. It is possible to have systemic sac pressures without evidence of endoleaks on CT or angiography.

Perioperative beta-blocker withdrawal and mortality in vascular surgical patients.

OBJECTIVE: Our purpose was to determine the effect of postoperative beta-blocker withdrawal on mortality and cardiovascular events after vascular surgery. METHODS: Detailed data were collected on perioperative cardiovascular medication use and discontinuation and cardiovascular risk factors among consecutive major vascular surgical procedures at two university hospitals. RESULTS: A total of 140 patients received beta-blockers preoperatively. Mortality in the 8 patients who had beta-blockers discontinued postoperatively (50%) was significantly greater than in 132 patients who had beta-blockers continued (1.5%, odds ratio 65.0, P<.001). The effect of beta-blocker discontinuation was unaffected by adjustment by stratification for risk factors (all P< or =.01), for contraindications to restarting beta-blockers (P = .006), and by multivariable analyses adjusting for potential confounders (adjusted odds ratio 17.0, P =.01). beta-Blocker discontinuation also was associated with increased cardiovascular mortality (0% vs 29%, P =.005) and postoperative myocardial infarction (odds ratio 17.7, P =.003). CONCLUSION: Discontinuing beta-blockers immediately after vascular surgery may increase the risk of postoperative cardiovascular morbidity and mortality.

Adenoviral-mediated uteroglobin gene transfer inhibits neointimal hyperplasia after balloon injury in the rat carotid artery.

OBJECTIVE: Uteroglobin is a protein with potent anti-inflammatory and immunomodulatory effects. We hypothesize that induction of uteroglobin expression in the artery wall by local adenoviral gene transfer will decrease neointimal hyperplasia in the rat carotid artery after balloon injury. METHODS: Seven male Sprague-Dawley rats underwent balloon injury of the common carotid artery. After the injury, with flow occluded, the artery was instilled with 50 microL of the adenoviral vector encoding uteroglobin gene (Ad.UG) at a concentration of 1.35 x 10(11) pfu/mL (n = 7) or 0.68 x 10(11) pfu/mL (n = 7) (n = 7). Control animals were similarly treated: either an adenovirus encoding for beta-galactosidase gene (Ad.LacZ) at 1 x 10(11) pfu/mL (n = 7) or the phosphate-buffered saline (PBS) vehicle (n = 6) was used. The solution was allowed to dwell for 20 minutes. The rats were humanely killed after 14 days by perfusion fixation, and the carotid arteries were sectioned for analysis with computerized planimetry. The intima-media area ratios were calculated for each artery and compared with analysis of variance with Bonferroni/Dunn post hoc testing. One additional rat from the PBS, Ad.LacZ, and Ad.UG (1.35 x 10(11) pfu/mL) groups was humanely killed 4 days after treatment for carotid artery protein extraction and Western blotting. RESULTS: Uteroglobin protein production was confirmed in the Ad.UG-treated arteries with Western blotting. Morphometric analysis showed that the Ad.UG group at 1.35 x 10(11) pfu/mL had a significantly lower intima-media area ratio than both the Ad.LacZ (P =.002) and PBS (P =.004) controls. The Ad.UG group at 0.68 x 10(11) pfu/mL was also significantly different from the Ad. LacZ (P =.003) and PBS (P =.006) controls. There was no statistical difference between the two control groups or between the two Ad.UG groups. CONCLUSION: Adenoviral gene transfer of uteroglobin, delivered intraluminally after arterial injury causes the production of uteroglobin protein and has an inhibitory effect on neointimal accumulation in the rat model.

Relationship between preoperative patency of the inferior mesenteric artery and subsequent occurrence of type II endoleak in patients undergoing endovascular repair of abdominal aortic aneurysms.

OBJECTIVES: The purpose of this study was (1) to find out whether preoperative inferior mesenteric artery (IMA) patency (on radiographic imaging) predicts IMA-related endoleaks after endovascular repair of infrarenal abdominal aortic aneurysms, (2) to determine feasibility of measuring aneurysm sac pressures in patients with endoleaks, and (3) to report early evidence of effective endovascular obliteration of IMA endoleaks. METHODS: We studied 76 consecutive cases of infrarenal aortic aneurysms that were repaired with an endovascular approach (March 1998-April 1999). RESULTS: There were 13 (17%) endoleaks persistent 30 days after the procedure. Eleven (85%) of these 13 were IMA-related endoleaks, which were documented with selective superior mesenteric artery angiography. The preoperative finding (on computed tomographic scan) of a patent IMA does not always predict an IMA-related endoleak, but results in a statistically and clinically significant higher ratio of patients with IMA-related endoleaks in the immediate postoperative period (24% versus 3%, P <.035). In eight of the 11 patients with persistent IMA-related endoleaks, measurement of intra-aneurysm sac pressures was possible, and six of these patients had systemic pressures within the excluded aneurysm sac. Nine (82%) of 11 IMA-related endoleaks were successfully obliterated by means of selective IMA embolization. CONCLUSIONS: Many endoleaks are caused by a patent IMA, and this can result in persistence of systemic pressure within the aneurysm sac. The preoperative finding (on computed tomographic scan) of a patent IMA is a predictor of increased rates of IMA endoleaks, and IMA endoleaks can be successfully obliterated through endovascular procedures, after endovascular abdominal aortic aneurysm repair.

Diagnosis and treatment of inferior mesenteric arterial endoleaks after endovascular repair of abdominal aortic aneurysms.

PURPOSE: To review the incidence and repair of inferior mesenteric arterial (IMA) type II endoleaks after endovascular repair of abdominal aortic aneurysms. MATERIALS AND METHODS: Fifty patients who underwent endovascular repair of abdominal aortic aneurysms were examined. If an endoleak was identified at 30-day postoperative computed tomography, conventional arteriography was performed to identify and eliminate its source. After the exclusion of attachment site leaks, a catheter was placed selectively in the superior mesenteric artery (SMA). If retrograde filling of the IMA and aneurysm was identified, coil embolization was attempted through the SMA and middle colic artery. Intrasac pressures were measured at embolization. RESULTS: Eight of 50 patients (16%) had type II endoleaks that were attributed to retrograde flow in the IMA. Intrasac measurements demonstrated systemic pressure in six patients and one-half systemic pressure in two patients. The IMA was embolized through the SMA and left colic artery in seven patients and through the translumbar aorta in one patient. CONCLUSION: Retrograde flow in the IMA is responsible for many type II endoleaks. Systemic pressures are transmitted into the aneurysm sac from the IMA. The IMA can be embolized successfully with an SMA approach in most patients.

Adenoviral-mediated expression of antisense RNA to basic fibroblast growth factor reduces tangential stress in arterialized vein grafts.

PURPOSE: The purpose of this study was to test whether basic fibroblast growth factor (bFGF) participates in arterialized vein graft remodeling. METHODS: Rabbits underwent in vivo gene transfer and carotid interposition vein grafting. Segments of external jugular vein were infected with an adenovirus that expressed antisense bFGF RNA (Ad.ASbFGF) at 1 x 10(10) PFU/mL to inhibit new synthesis of bFGF by cells in the vein graft wall. Control rabbits were treated with either adenovirus that encoded beta-galactosidase (Ad.lacZ) at 1 x 10(10) PFU/mL or vehicle (phosphate-buffered saline solution [PBS]). At 3 days, 3 grafts per treatment group were harvested for the determination of gene expression of ASbFGF RNA by reverse transcriptase-polymerase chain reaction. Rabbits were killed, and perfusion was fixed 2 months after the grafting. Total wall thickness and lumen circumference of vein grafts and normal arteries were measured in cross sections. Calculated mean tangential stress (+/-SD) for the ASbFGF-treated group and controls was compared for significance. Grafts were immunohistochemically stained to assess bFGF protein production. RESULTS: Only the grafts infected with the Ad.ASbFGF gene expressed ASbFGF RNA. Grafts that were treated with Ad.ASbFGF displayed lower tangential stress (10.9 +/- 2.3 dynes/cm(2)) than PBS alone (22 +/- 2.8 dynes/cm(2)) or Ad. lacZ-treated controls (20.6 +/- 5.4 dynes/cm(2); P <.001). Tangential stress in the Ad.ASbFGF group was comparable to a normal carotid artery (13.9 +/- 2.1 dynes/cm(2)). The difference in mean total wall thickness was significant among the 3 treatment groups: Ad.ASbFGF, 164 +/- 3.4 microm); Ad.lacZ, 100 +/- 3.3 microm; and PBS, 96 +/- 3.6 microm; P <.01). Luminal circumference was not different among the groups. The Ad.ASbFGF-treated vein graft wall was composed of thick layers of concentric smooth muscle cells and elastin fibers in contrast to the sponge-like appearance observed in control arterialized vein grafts. Reduction in bFGF protein was noted only in the Ad.ASbFGF-treated group. CONCLUSION: Inhibition of bFGF synthesis in vivo with the use of adenoviral gene transfer of antisense RNA to bFGF promotes a vein graft with decreased tangential stress while maintaining the luminal area. The vein graft wall is remodeled and qualitatively resembles an artery so that wall tangential stress in Ad.ASbFGF and normal artery are not significantly different. The lack of significant difference in lumen circumference among groups suggests that wall thickening in the Ad. ASbFGF grafts is not at the expense of luminal narrowing. Our results suggest that ASbFGF RNA expression may represent an effective strategy in limiting the failure of arterialized venous conduits.

The calibration and validation of a phase-modulated near-infrared cerebral oximeter.

OBJECTIVE: This study was undertaken to compare the cerebral oxygenation measured by an experimental phase-modulated near-infrared (NIR) spectroscopy system with capillary saturation estimated from jugular venous oxygen saturation. METHODS: Jugular venous catheters were placed in 30 patients undergoing carotid endarterectomy and 194 measurements of venous oxygen saturation were obtained intra operatively. Simultaneous measurement of optical path length at 754, 785, and 816 nm was performed using a phase-modulated near-infrared spectroscopy system. Optical calibration was performed using both an optical bench and a scattering mold. Hemoglobin saturation was calculated from NIR measurements using equations derived from diffusion theory. Capillary saturation was calculated from the arterial and venous saturations. RESULTS: Jugular venous saturations ranged from 41 to 92%. When calibrated using the optical bench, the NIR estimates of hemoglobin saturation deviated from estimated capillary values by an average of 2.6% bias and 4.3% deviation. No systematic bias was noted. NIR values derived from mold calibration were less accurate and precise (4.6% bias and 6.9% deviation.) Use of the initial venous sample as an in vivo calibration improved the accuracy of the mold calibration but did not alter the performance of the bench calibration. CONCLUSIONS: Under the conditions tested, an experimental phase-modulated near-infrared spectroscopy system calibrated using an optical bench agreed with capillary saturation estimated from jugular venous samples. Further work is necessary to demonstrate valid performance of the system under other conditions.

Gene therapy.

Gene therapy for vascular disease is in the beginning stages. Each year investigators are increasing our understanding of the molecular and cellular biology of vascular disease and its complications. Our genes exert exquisite control over the expressed molecular pattern that results in biological function and pathology. Gene transfer techniques can be used to affect the pattern of gene expression. Gene therapy is a powerful tool that will allow specific manipulation of the genetic cascade that determines biological function. Gene transfer techniques should help to define the molecular mechanisms involved in vascular pathology, such as atherosclerosis and its complications. Currently, gene therapy has only reached clinical trials, but this new technology will likely play a major role in our treatment of vascular problems in the future. An understanding of the significance of this new technology is important for both health care providers and patients.

Native atherosclerosis and vein graft arterialization: association with increased urokinase receptor expression in vitro and in vivo.

Interaction of proteases with cell surface receptors may modulate cell adhesion, migration, invasion, and matrix degradation. Since the plasminogen activator system has been hypothesized to play a role in intimal thickening after various types of vascular injury, we first studied the expression of urokinase receptor (u-PAR) protein and mRNA by smooth muscle cells (SMC) grown in explant cultures from normal and diseased vessels. Using equilibrium binding studies with radiolabeled 125I-labeled single chain urokinase-type plasminogen activator (scu-PA), we determined that SMC cultured from atherosclerotic arteries expressed a higher maximal number of binding sites/cell (3.6 +/- 0.4 x 10(5) sites/cell vs. 2.1 +/- 0.3 x 10(5), +/- SEM, p < 0.05) with a similar affinity (Kd = 1.5 +/- 0.1 vs. 1.2 +/- 0.2 nM, p = ns). However, SMC subcultured from diseased saphenous vein grafts expressed the highest levels of u-PAR compared to SMC from normal saphenous vein (4.8 +/- 0.6 x 10(5) sites/cell vs. 1.6 +/- 0.9 x 10(5), +/- SEM, p < 0.05). Using binding studies and Northern analysis, we demonstrated a dose and time dependent upregulation of u-PAR protein and mRNA expression respectively in human SMC in response to serum stimulation. Using a rabbit specific u-PAR cDNA probe, we demonstrated a similar upregulation of u-PAR mRNA both in rabbit aortic SMC in culture in response to serum stimulation and up to a 20 fold increase in u-PAR mRNA in rabbit jugular veins in response to implantation as arterial grafts in vivo. Finally, to confirm that u-PAR mRNA is upregulated in human vessels after injury, we performed immunohistochemistry and in situ hybridization studies on coronary arteries, normal saphenous veins and saphenous veins from 10 weeks to 13 years after implantation as grafts. u-PAR mRNA was found mainly in the periadventitial microcirculation in normal veins, but was found to be upregulated in the neointima and media of thickened veins in both macrophages and smooth muscle cells. SMC near the internal elastic laminae in diseased coronary arteries appeared to express increased u-PAR mRNA. These data suggest that this increased expression of u-PAR may contribute to early lesion development.

Antisense basic fibroblast growth factor gene transfer reduces early intimal thickening in a rabbit femoral artery balloon injury model.

PURPOSE: The purpose of this study was to determine whether endogenous basic fibroblast growth factor (bFGF) production contributes to the intimal hyperplastic response to injury in a model of rabbit femoral artery balloon injury. Inhibition of de novo production of bFGF protein was targeted by intramural adenoviral gene transfer of antisense bFGF (Ad.ASbFGF) RNA. The adenovirus was delivered locally intraluminally at the time of arterial injury. METHODS: New Zealand White rabbits underwent balloon injury of the superficial femoral artery, followed by intraluminal delivery of an adenoviral vector encoding a rat antisense bFGF (ASbFGF) transcript at a concentration of 1 x 10(10) plaque-forming units per milliliter. Control animals were treated in a similar fashion, using either an adenovirus encoding the lac Z reporter gene (Ad.lacZ) or phosphate-buffered saline solution (PBS; vehicle) alone. Two weeks after balloon injury, rabbits were killed and perfusion fixed. Femoral arteries were harvested for histomorphometric analysis. Intimal and medial wall thickness was measured at eight points around the vessel perimeter, and mean intimal/medial (I/M) thickness ratios were compared by analysis of variance and Student's t test. In addition, medial cell proliferation in Ad.ASbFGF and Ad.lacZ treated arteries was evaluated 4 days and 2 weeks after balloon injury by 5-Bromo-2'-deoxyuridine labeling. RESULTS: At 14 days (n = 25) after balloon injury, histomorphometric analysis revealed a significant inhibition of intimal thickening in Ad.ASbFGF-treated arteries as compared with Ad.lacZ-treated and PBS-treated controls (I/M thickness ratios +/- SD, 0.43 +/- 0.22 for Ad.ASbFGF vs 1.03 +/- 0.28 for Ad.lacZ and 0.86 +/- 0.19 for PBS; p < 0.0001 and p = 0.004, respectively). There was no significant difference in the I/M thickness ratios of Ad.lacZ-treated and PBS-treated vessels (p = 0.27). Although there was no significant difference in the proliferation index of Ad.ASbFGF-treated and Ad.lacZ-treated vessels 4 days after injury, an increase in apoptosis was noted in the Ad.ASbFGF-treated vessels 4 days after balloon injury. CONCLUSIONS: The use of ASbFGF RNA gene transfer, designed to inhibit de novo bFGF synthesis after balloon injury, results in a significant inhibition of neointimal formation. This suggests that continued bFGF synthesis contributes to the arterial response to injury in rabbits. ASbFGF gene transfer may be an effective strategy in limiting the intimal hyperplastic response after vascular reconstructive procedures.

Management of pancreaticoduodenal artery aneurysms presenting as catastrophic intraabdominal bleeding.

BACKGROUND: Pancreaticoduodenal artery aneurysms (PDAs) are rare, accounting for only 2% of all visceral artery aneurysms. The majority of reported cases of patients with PDA have presented subsequent to rupture. Presentation without rupture also has been reported and is often associated with abdominal discomfort or diagnosed incidentally on radiologic studies. PDA rupture is associated with a high mortality rate, with fatal bleeding into the retroperitoneal space, intraperitoneal cavity, or gastrointestinal tract. METHODS: This article reports two cases of ruptured PDA, both presenting as catastrophic intraabdominal bleeding and both treated successfully at celiotomy. In addition, the literature concerning PDA is reviewed. RESULTS: Only 11 cases of PDA associated with sudden, severe abdominal pain and shock have been described. The mortality rate in these 11 cases was 36%, with half the patients not reaching the operating room alive. Successful management includes rapid resuscitation and control of the bleeding site with minimal pancreatic dissection, angiography for confirmation of vascular control and anatomic localization, and further definitive treatment if obliteration is incomplete. CONCLUSIONS: The aneurysm should be obliterated whenever possible to avoid both rebleeding and local complications related to mass effect such as pancreatic duct obstruction or erosion of the mass into neighboring structures. With appropriate and expeditious treatment, these gravely ill patients can be managed effectively and good outcomes obtained.