Duplex criteria for determination of 50% or greater carotid stenosis.

Recently the North American Symptomatic Carotid Endarterectomy Trial investigators reported a benefit of carotid endarterectomy compared with medical therapy for symptomatic patients with 50% or greater carotid stenosis. This has necessitated the development of screening parameters for diagnosis of 50% or greater carotid stenosis on the basis of the reference standards used in the study by the North American Symptomatic Carotid Endarterectomy Trial. The duplex scans and arteriograms of 110 patients (210 carotid arteries) were reviewed by blinded readers. Duplex measurements of peak systolic velocity and end diastolic velocity were recorded, and the ratio of these velocities in the internal and common carotid arteries was calculated. The criteria determined for detection of 50% or greater stenosis were as follows: peak systolic velocity of the internal carotid artery greater than 170 cm/s (sensitivity, 92%; specificity, 90%; positive predictive value, 92%; negative predictive value, 90%; and accuracy, 91 %); end diastolic velocity of the internal carotid artery greater than 60 cm/s (sensitivity, 92%; specificity, 86%; positive predictive value, 95%; negative predictive value, 79%; and accuracy, 91 %); ratio of peak systolic velocity of the internal carotid artery to peak systolic velocity of the common carotid artery greater than 2 (sensitivity, 93%; specificity, 75%; positive predictive value, 83%; negative predictive value, 89%; and accuracy, 85%); and ratio of end diastolic velocity of the internal carotid artery to end diastolic velocity of the common carotid artery greater than 2.4 (sensitivity, 96%; specificity, 79%; positive predictive value, 88%; negative predictive value, 92%; and accuracy, 89%). It is concluded that 50% or greater carotid artery stenosis can be reliably determined by duplex criteria. The use of receiver operating characteristic curves allows the individualization of duplex criteria to the clinical situation.

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.

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.

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.

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.

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.

Thermal preconditioning before rat arterial balloon injury: limitation of injury and sustained reduction of intimal thickening.

Heat shock proteins (HSPs) are a family of highly conserved proteins, essential to cell survival, that are induced during times of physiological stress. These proteins, when induced, can provide tolerance to subsequent injury. Several studies have documented that HSPs play an important role in the response of vascular cells to injury or stress. Whether the vasculature itself can be effectively preconditioned before arterial injury is unknown. Vascular HSP induction by whole-body hyperthermia (WBH) was evaluated with regard to its effects on the vascular response to balloon injury. WBH treatment of Sprague-Dawley rats (colonic temperatures of 41 to 42 degrees C for 15 minutes) resulted in maximal arterial HSP expression within 8 to 12 hours. Rats (male, 300 g, n=59) were randomly assigned to undergo either WBH or no treatment 8 hours before standard carotid balloon injury. At 14 (n=26) and 90 (n=21) days after balloon injury, histomorphometric analysis revealed a significant limitation of intimal accumulation in preconditioned arteries as compared to controls (intimal/medial area ratios+/-SEM: 14 days, 0.57+/-0.07 versus 0.86+/-0.08, P=0.01; 90 days, 0.78+/-0.12 versus 1.19+/-0.14, P<0.05). The medial cell proliferation index at 4 days (n=12) was significantly reduced in the treated group as well (3.6+/-0.9% versus 7.2+/-1.3%, P<0.05). Conversely, the mean total cell number in the media of heated arteries was higher (393+/-20 versus 328+/-17, P<0.05). Vascular preconditioning with brief WBH induces a heat shock response in the arterial wall that is associated with a significant and sustained reduction in intimal accumulation. This effect appears to be due in part to preservation of medial cell integrity and limitation of the proliferative response. These results suggest that thermal preconditioning of vascular tissue may be an effective strategy to improve long-term results after revascularization procedures.

Antisense basic fibroblast growth factor gene transfer reduces neointimal thickening after arterial injury.

PURPOSE: To determine whether synthesis of endogenous basic fibroblast growth factor (bFGF) after arterial injury is critical to the intimal thickening response, intraluminal adenoviral gene transfer of an antisense bFGF (Ad.ASbFGF) transgene was used to inhibit the subsequent synthesis of bFGF protein after injury. METHODS: Sprague-Dawley rats underwent balloon catheter carotid artery injury and in vivo gene transfer. Isolated segments of rat common carotid artery were infected with an adenoviral vector encoding an antisense bFGF transcript at concentrations of 2 x 10(9), 1 x 10(10), or 1 x 10(11) pfu/ml. Control rats were treated with either a control adenovirus encoding the beta-galactosidase gene, (Ad.lacZ), at 1 x 10(10), or 1 x 10(11) pfu/ml, or phosphate-buffered saline solution (vehicle). Two weeks after injury the rats were killed and perfusion-fixed. Cross-sectional areas of the carotid arterial intima and media were measured by planimetry, and the intima/media ratio (I/M) was calculated for each vessel. RESULTS: The mean I/M for each Ad.ASbFGF group and controls were compared and the significance assessed by analysis of variance. At two weeks after injury, the highest dose of Ad.ASbFGF, 1 x 10(11) pfu/ml, resulted in a near total inhibition of thickening (I/M = 0.14 +/- 0.04, mean +/- SEM) when compared with phosphate-buffered saline solution alone (I/M = 0.99 +/- 0.07), or Ad.lacZ 1 x 10(10) pfu/ml (I/M = 1.01 +/- 0.10) control treatments (p < 0.01). A tenfold lower dose of Ad.ASbFGF, 1 x 10(10) pfu/ml, also caused significant reduction in intimal thickening (I/M = 0.39 +/- 0.07, p < 0.01). Treatment with 2 x 10(9) pfu/ml Ad.ASbFGF did not significantly limit intimal thickening (I/M = 0.72 +/- 0.12). CONCLUSIONS: Inhibition of bFGF synthesis in vivo using an antisense RNA strategy significantly inhibits intimal thickening after arterial balloon injury. This study suggests that continued bFGF synthesis contributes to intimal thickening after arterial injury, and that antisense bFGF may represent an effective strategy in limiting restenosis after angioplasty.

Low dose heparin therapy: in vitro verification of antithrombotic effect.

Low dose heparin therapy has been used routinely for prophylaxis of deep venous thrombosis, yet in vitro data regarding its antithrombotic effects are sparse. The effects of heparin on venous thrombus formation were studied in an in vitro perfusion system. Fresh blood collected from human volunteers was treated with varying heparin doses and perfused at a shear rate of 100 sec-1 over everted, injured porcine vein segments, simulating conditions in the venous circulation. Platelet and fibrin deposition were measured by use of indium 111 and iodine 125 radiolabels, respectively. The effects of heparin on the intrinsic coagulation cascade were monitored by the activated clotting time. Increasing doses of heparin resulted in significant reductions in fibrin and platelet deposition (ANOVA F = 2.67 and 3.17, respectively, p less than 0.05). At a dose of only 0.19 USP units/ml blood, equivalent to a 1000 unit bolus of heparin in a 70 kg man, a noticeable reduction in both fibrin and platelet deposition was observed without an increase in the activated clotting time. These data confirm the antithrombotic effects of heparin at low dose ranges and may explain the clinically observed phenomenon of deep venous prophylaxis without an appreciable alteration in the conventional coagulation assays.