Multicentre study of abdominal aortic aneurysm measurement and enlargement.

BACKGROUND: No effective treatment is currently available to prevent progression of small and medium-sized abdominal aortic aneurysms (AAAs). Identification of drugs with sufficient promise to justify large expensive randomized trials remains challenging. One potentially useful strategy is to look for associations between commonly used drugs and AAA enlargement in appropriately adjusted observational studies. METHODS: Potential AAA measurements were identified from abdominal imaging reports in the electronic data files of three medical centres from 1995 to 2010. AAA measurements were extracted manually and patients with an aneurysm of 3 cm or larger, who had at least two measurements over an interval of at least 6 months, were identified. Other data were obtained from the electronic data files (demographics, co-morbidities, smoking status, drug use) to conduct a propensity analysis of the associations of drugs and other factors with AAA enlargement. RESULTS: From 52,962 abdominal imaging studies, 5362 patients with an AAA of 3 cm or more were identified, of whom 2428 had at least two measurements over at least 6 months. Mean AAA follow-up was 3.4 years and the mean AAA enlargement rate was 2.0 mm per year. Propensity analysis demonstrated no significant association of AAA enlargement with statins, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Diabetes was associated with a reduction in AAA enlargement of 1.2 mm per year (P = 0.008), and chronic obstructive pulmonary disease was associated with increased enlargement (0.5 mm per year; P = 0.050). Moderate AAA measurement variation and substantial terminal digit preference were also observed, but the digit preference became less pronounced after 2000. CONCLUSION: This study confirms the negative association of diabetes with AAA progression. There was no evidence that commonly used cardiovascular drugs affect AAA enlargement.

Imaging arterial thrombosis: comparison of technetium-99m-labeled monoclonal antifibrin antibodies and indium-111-platelets.

UNLABELLED: Imaging with the 99mTc-T2G1s monoclonal antifibrin antibody fragment (Fab') has demonstrated promise in the noninvasive detection of venous thrombi in humans. The purpose of this study was to determine whether chronic arterial thrombi can also be detected by antifibrin antibody imaging. METHODS: Eighteen subjects with chronic arterial thrombi were studied with planar and tomographic imaging at 0 to 24 hr postinjection of 99mTc-labeled T2G1s monoclonal antifibrin antibody fragment. Imaging with 111In-labeled platelets was also performed. Images were visually graded by two observers as 0, 1, 2 or 3 (no, faint, moderate or marked) uptake, and quantitative analysis of tomographic images was done in 13 subjects. RESULTS: On visual analysis of planar images, 44% (8 of 18) of antifibrin patient studies were 1.0 or more and 66% (10 of 18) were judged negative compared with 94% (15 of 16) of platelet patient studies judged 1.0 or more and 6% (1 of 16) judged as negative (p < 0.01). Visual analysis of tomographic images was similar, with 61% (11 of 18) of antifibrin studies graded 1.0 or more compared with 100% (17 of 17) of platelet studies (p < 0.01). The tomographic target-to-background ratio was higher with platelets than with antifibrin antibody (2.5 +/- 1.4 versus 1.8 +/- 1.0, p < 0.05). CONCLUSION: In the large-vessel chronic arterial thrombi studied, the results of 99mTc-labeled monoclonal T2G1s antifibrin Fab' imaging were positive in only one-half of the patients studied, significantly less than the findings with platelet imaging, which were positive in all subjects. The higher rate of positive images with labeled platelets than with labeled antifibrin antibodies may be largely due to thrombus age, with continued platelet deposition but little active fibrin deposition.

Conventional versus high-porosity polytetrafluoroethylene grafts: clinical evaluation.

In baboons, nonreinforced (unwrapped) 60 microns internodal distance polytetrafluoroethylene grafts form a complete endothelial lining within 2 weeks by capillary ingrowth through the wall. Smooth muscle cells then grow under the endothelium and proliferate to form a complete neointima. To determine if spontaneous endothelialization of these grafts can also occur in humans, 10 above-knee femoropopliteal grafts composed of equal lengths of 60 and 30 microns polytetrafluoroethylene were placed in eight patients. These grafts were reinforced (wrapped) for human use. Because biopsy of the grafts was not possible, endothelialization was assessed noninvasively by 111In-labeled platelet imaging 1 week and 3 months after surgery. There was no difference in indium uptake between 60 and 30 microns segments at either time. Histologic sections were available from 60 microns segments of two patients who underwent operation for graft thrombosis. Capillary ingrowth was seen in these grafts, but it rarely extended more than half the distance from the outside of the graft to the lumen. Smooth muscle cells were not seen on the flow surface, indicating that a neointima had not formed. These findings demonstrate that capillary ingrowth can occur in 60 microns grafts in humans but does not produce an endothelial lining. The failure to endothelialize is perhaps a result of inadequacy of angiogenesis in adult humans or retardation of capillary ingrowth by the reinforcing wrap.

Effect of aspirin and dipyridamole on the patency of lower extremity bypass grafts.

Recent clinical studies indicate that the use of aspirin and dipyridamole improves graft patency rates in patients with infrainguinal polytetrafluoroethylene (PTFE) grafts and aortocoronary vein grafts. We undertook a prospective, double-blind, randomized study to determine whether these drugs administered postoperatively to patients with PTFE or autologous vein infrainguinal bypasses would improve graft patency during the first 24 months after operation. Patients received either aspirin 325 mg and dipyridamole 75 mg or identical placebo tablets three times a day, taken orally. Patency rates were compared by computing standard life tables and comparing cumulative patency rates. One hundred patients with 102 grafts were studied. The cumulative patency rate at 24 months was not significantly different for the treatment (57%) versus control (67%) groups or for any subgroup. We conclude that aspirin and dipyridamole administered postoperatively in the doses used in this study do not improve the overall patency rates of vein or PTFE infrainguinal bypass grafts.

Mechanism of long-term degeneration of arterialized vein grafts.

This study examined long-term changes in the morphology and cellular kinetics of rabbit vein grafts transplanted into the carotid artery. Six grafts were studied 1 year after implantation. Although the circumference and thickness of the wall were not different than at 12 weeks, degenerative changes occurred. The endothelial lining of the graft appeared intact, but large segments of the graft surface no longer excluded Evans blue dye, suggesting increased permeability. Collections of red blood cells were noted within the intima. Several grafts had extensive subendothelial fibrin deposits, often associated with foam cells, and evidence of previous hemorrhage, but these changes did not stimulate significant smooth muscle cell proliferation. Increased permeability with entrance of proteins and erythrocytes into the intima may result from increased wall tension or from low shear rates at the wall. Similar changes may lead to atherosclerosis in human vein grafts at late times.

Role of arteriography in the preoperative evaluation of carotid artery disease.

This retrospective study was undertaken to determine the role of arteriography in the treatment of patients being considered for carotid endarterectomy. The results of preoperative classification of disease severity by duplex ultrasound and arteriography were compared, and the impact of arteriography on patient management was ascertained. We reviewed the records of 83 patients who had carotid surgery planned on the basis of their clinical history and duplex scan results and who then underwent arteriography. Duplex scan results agreed with the classification of stenosis by arteriography in 87% of evaluated sides and were within one category in 98%. In 87% of the cases reviewed, the clinical presentation and duplex scan findings were sufficient for appropriate patient management. In the instances that arteriography was useful (13%), the need for arteriography was evident when the duplex scan (1) was technically inadequate or equivocal; (2) showed an unusual distribution of disease, atypical anatomy, or a recurrent lesion; or (3) demonstrated an internal carotid artery with diameter-reducing stenosis of less than 50% in a patient with hemispheric neurologic symptoms despite antiplatelet therapy.

Effect of micropore filtration on pulmonary function after massive transfusion.

1. This study demonstrates a positive correlation between the number and size of infused microaggregates and the subsequent abnormality in pulmonary function as measured by oxygenation and dead space. 2. No such correlation between the severity of injury and the altered pulmonary function or transfusion volume was demonstrated. 3. We were unable to demonstrate an advantage to the use of a 40 mu micropore filter in preventing the adult respiratory distress syndrome (ARDS) or in improving pulmonary function in our patients. 4. One explanation for the failure to demonstrate such an advantage is the low efficiency of the filter used.

Use of the vascular diagnostic laboratory in improving the success of angioaccess procedures.

The goal of hemodialysis access placement is long-term patency with as few revisions as possible. Autogenous fistulas have superior performance compared with prosthetic grafts, but up to 70% fail to mature sufficiently for dialysis. Accurate preoperative evaluation of arterial and venous anatomy can increase the successful use of autogenous fistulas, thereby increasing long-term access patency. Duplex ultrasonography has an important role in identifying usable autogenous conduit and detecting venous outflow disease, another important cause of access failure. The use of the vascular diagnostic laboratory in preoperative planning can increase the percentage of autogenous fistulas placed, increase the percentage that mature, and reduce the rate of negative explorations for vein at the time of surgery.

Variability in measurement of specific parameters for carotid duplex examination.

The variability of four carotid artery frequency parameters used for classifying disease with duplex scanning was prospectively studied. Forty-eight patients (94 patent carotid arteries) were each examined by two technologists. Measured parameters were the peak systolic frequency (PSF) and the first zero slope from the common carotid artery, and the PSF and end diastolic frequency (EDF) from the internal carotid artery. Measurements from all the examinations were made twice by each technologist. Interobserver, intraobserver, and interpatient variability in measurement of the first zero slope was so great that we have abandoned its use. Measurement of variability for PSF and EDF was much less (correlation coefficients 0.68 to 0.92). These parameters were measured with sufficient precision to warrant their continued use for important decision steps in classifying carotid artery disease. Interpatient differences in PSF sufficient to cause disagreement regarding the hemodynamic significance of carotid disease occurred in only three instances. In each of these cases the differences were due to examination technique (failure to identify a very distal internal carotid artery stenosis, difficulty distinguishing between a kink and a stenosis, and failure to recognize an improper Doppler angle). We conclude that the variability of PSF and EDF is within clinically acceptable levels and is mainly due to examination technique rather than measurement of waveform parameters or changes in patient hemodynamics.

Microangiopathic hemolytic anemia associated with hyperacute rejection of a kidney allograft.

A patient is described who developed severe microangiopathic hemolytic anemia associated with hyperacute rejection of a maternal renal allograft. The syndrome included profound anemia and thrombocytopenia, refractory to either blood or platelet transfusions, increased plasma hemoglobin levels and the appearance of circulating fibrin split products. All hemotologic abnormalities reversed themselves promptly following graft nephrectomy. The pathophysiology of this infrequent condition is discussed.

Management of internal carotid artery occlusion.

Although attempts to restore patency of occluded internal carotid arteries are now rarely made, endarterectomy in the contralateral artery, external carotid endarterectomy and until recently EC/IC bypass have remained surgical options in the management of such patients. Over a four-year period at this institution 104 patients underwent carotid endarterectomy for stenosis. In this group the contralateral carotid was patent (Group A). Fifty-four patients with unilateral carotid artery occlusion underwent contralateral endarterectomy (Group B), 8 underwent ECA/ICA bypass (Group C) and 4 an ECA endarterectomy (Group D). No statistically significant difference was noted in perioperative stroke and death rates for Groups A and B were (1% and 1%) and (3.7% and 1.9%) respectively. One Group C patient died from perioperative stroke (12.5%). For late events the life table adjusted annual rates for stroke and mortality were similar, Group A (stroke 2.1% and death 5%), and Group B (stroke 1.6% and death 5%). In Group C stroke rate was 10% and death 3%. All four patients undergoing ECA endarterectomy were relieved of their symptoms. It is concluded that in patients with internal carotid artery occlusion TEA may be performed with perioperative morbidity and mortality rates comparable to those when the opposite carotid artery is patent. The late outcome for stroke compares favorably with the reported natural history of the disease and outcome for such patients treated medically in the Joint Study of Extracranial Occlusion and EC-IC Bypass Study. External carotid artery endarterectomy appears useful in the treatment of embolic events on the occluded side. ECA/ICA bypass does not appear to confer benefit.

Flow affects development of intimal hyperplasia after arterial injury in rats.

This study examined the effects of blood flow on intimal hyperplasia after balloon catheter injury of the rat common carotid artery. Flow was altered by ligation of the opposite common carotid artery (increased flow) or of the ipsilateral internal carotid artery (decreased flow). Blood flow decreased by 35% in the low-flow group and increased by 29% in the high-flow group. Similar changes in mean velocity were observed. Cross-sectional intimal area was significantly greater in the low- than the high-flow group at 2 weeks (0.11 +/- 0.01 versus 0.06 +/- 0.01 mm2, p less than 0.01) and 4 weeks (0.17 +/- 0.02 versus 0.12 +/- 0.01 mm2, p = 0.01) but not at 1 or 8 weeks. Smooth muscle cell proliferation rates (thymidine labeling indexes) were not different in high- and low-flow groups at 2 days and at 1 and 4 weeks. Matrix accumulation at 2 and 4 weeks was the same in both groups. Mature neointima did not respond to changes in flow; when vessel ligation was delayed until 2 months after injury, there was no effect on neointimal area. These data indicate that early neointimal hyperplasia is increased when flow is reduced, possibly because of alteration of smooth muscle cell migration.

Central venous catheter failure is induced by injury and can be prevented by stabilizing the catheter tip.

PURPOSE: Thrombosis associated with central venous catheters is a significant cause of device failure, morbidity, and loss of access sites. We hypothesized that central vein thrombosis is caused by catheter injury to the vein wall and that it can be reduced by stabilizing the catheter tip. To test these hypotheses, we studied central vein catheters in a porcine model. Test catheters had a silicone-encased stainless steel loop at the indwelling end that contacted the vein wall and stabilized the catheter tip in the center of the vessel. METHODS: Sealed silicon elastic (Silastic) catheters (3.2 mm outer diameter) with and without a stabilizing loop were inserted via the external jugular vein into the superior vena cava just above the right atrium. Animals were killed at 1, 2, 4, and 8 weeks, and the vena cava was inspected for the presence of thrombus and entrapment of the catheter tip. RESULTS: In control animals mural thrombus developed at the site of the catheter tip. This thrombus organized by invasion of macrophages and smooth muscle cells, eventually forming a lesion similar to intimal hyperplasia. Lesion cross-sectional area was significantly smaller in animals with loop catheters than in control animals at 2 weeks (1.2 +/- 1.3 vs 34.5 +/- 23.9 mm2; p = 0.05) and 4 weeks (2.8 +/- 0.3 vs 13.9 +/- 5.8 mm2; p < 0.05). By 8 weeks the vena cava was nearly occluded in most animals and the catheter tip was entrapped in this lesion in all cases. Test catheters eliminated the injury process for up to 8 weeks (p < 0.01, chi2 control vs loop catheter entrapment). Very little injury response was found where the loop contacted the vein wall, and the catheter tip was free of thrombus in all cases. CONCLUSIONS: Mural thrombosis at the tip of indwelling central catheters is caused by chronic mechanical venous wall injury. Vessel injury and the resulting thrombosis can be prevented by a catheter modification that stabilizes the tip. Such a catheter may significantly reduce catheter malfunction and morbidity associated with these devices.

Dialysis access failure: A sheep model of rapid stenosis.

PURPOSE: Intimal hyperplasia at the venous anastomosis of dialysis access grafts causes early failure, although increased flow inhibits intimal hyperplasia in arterial grafts and after vessel injury. We designed a sheep model to study this process. METHODS: Polytetrafluoroethylene (PTFE) grafts were placed in the necks of sheep from the carotid artery to the external jugular vein. Grafts were harvested after perfusion fixation at 4, 8, and 12 weeks and submitted for histologic and immunohistochemical examination, including morphometry of neointimal lesions. RESULTS: The venous anastomoses developed thick neointima within the PTFE graft by 4 weeks. Lesions at the venous end were significantly thicker than those at the arterial end by 8 weeks (1.2 +/- 0.1 vs 0.38 +/- 0.05 mm, P <.02) and had greater cross-sectional area at both 4 (0.32 +/- 0.21 vs 3.6 +/- 0.8 mm(2), n = 7, P <.02) and 8 weeks (9.8 +/- 1.9 vs 1.1 +/- 0.7 mm(2), n = 7, P <.02). Only one of the four grafts (25%) in the 12-week group remained patent. Lesions were composed of smooth muscle cells, matrix, and thrombus of various ages. Cellular proliferation was prominent in neointima adjacent to thrombus and in granulation tissue surrounding the graft. Organizing thrombus contributed significantly to luminal narrowing. CONCLUSION: The sheep model of dialysis access reliably produces venous stenosis within 4 weeks. Lesions develop in the absence of uremia, graft puncture, or dialysis, suggesting that these factors are not necessary for graft failure. The continued presence of thrombus and high rates of cellular proliferation suggest ongoing injury is an important cause of lesion formation. This model allows study of the cellular mechanisms of dialysis failure.

Cerebrovascular accident after Greenfield filter placement for paradoxical embolism.

A 69-year-old man with paradoxical embolism suffered a cerebral embolism despite treatment with anticoagulants and placement of a Greenfield filter. The open architecture of the filter allows it to maintain caval patency better than other mechanical devices, but this design also permits passage of emboli up to 3 mm in diameter. Although such small emboli do not produce symptoms in the pulmonary circuit, they can be devastating in the cerebral circulation. For this reason, the Greenfield filter may be inadequate treatment for paradoxical embolism. Ligation of the inferior vena cava is proposed as an alternative that provides better protection against small emboli.

The effect of rigid external support on vein graft adaptation to the arterial circulation.

In previous experiments vein graft wall thickening stopped when the ratio of lumen radius to wall thickness equaled that of a normal artery. This led us to postulate that wall stress, which this ratio determines, regulates wall structure. To test this hypothesis we studied the effect of decreasing lumen radius and acutely diminishing wall stress with a rigid, external support. Jugular vein grafts were interposed into the carotid artery of rabbits. The proximal half of the grafts was wrapped with a polytetrafluoroethylene graft. Twelve veins received a tight wrap (2.5 or 3 mm diameter) that decreased the graft diameter, and four received a loose wrap (5 mm diameter) that did not. These grafts were fixed by perfusion after 1 day, 11 days, or 12 weeks. Wall thickness was slightly less in all tight-wrap segments. Total cross-sectional wall area, smooth muscle cell volume, and matrix deposition were significantly reduced in tight-wrap segments. These differences were greatest at 11 days. The observation that narrowing and external support of these vein grafts causes reduction of wall area supports the hypothesis that increased wall stress might be an important stimulus for wall thickening.

Duplex scanning of normal or minimally diseased carotid arteries: correlation with arteriography and clinical outcome.

This study evaluated the role of duplex scanning in the management of patients with normal or minimally diseases carotid arteries. Carotid duplex scans were interpreted according to previously established criteria and considered normal when pulsed Doppler spectral waveforms showed laminar flow or only minor flow disturbances. Normal flow patterns were noted by duplex scanning in 100 carotid bifurcations of 72 patients who also underwent carotid arteriography. Neurologic symptoms (amaurosis fugax, transient ischemic attack, or stroke) were present in relation to 23 arteries and absent in relation to 77 arteries. On the 23 symptomatic sides arteriography was interpreted as normal in eight, 1% to 15% stenosis in 14, and 16% to 40% stenosis in one. For the 77 asymptomatic sides, arteriography showed normal vessels in 15, 1% to 15% stenosis in 43, and 16% to 40% stenosis in 19. One symptomatic patient was treated by carotid endarterectomy for an irregular 1% to 15% stenosis. None of the asymptomatic lesions were in the range of 80% to 99% stenosis, which would justify endarterectomy for asymptomatic disease. Clinical follow-up for a mean interval of 28 months on 20 of the 22 symptomatic patients not undergoing surgery revealed no strokes and transient recurrent symptoms in two patients. Assuming that the single operation in this study was indicated, duplex scanning correctly identified lesions not requiring carotid endarterectomy in 96% (22/23) of the symptomatic patients. A normal duplex scan also predicted a benign clinical outcome without operation. Duplex scanning can reliably exclude surgically treatable carotid bifurcation lesions in asymptomatic patients, and endarterectomy is rarely indicated in symptomatic patients with normal duplex scan results. This study supports a nonoperative therapeutic approach for most patients with neurologic symptoms and a normal carotid duplex scan on the appropriate side.

Diagnosis by computed tomography of arteriovenous fistula complicating ruptured iliac artery aneurysm.

Isolated iliac artery aneurysms comprise less than 1% of all arteriosclerotic aneurysms. Spontaneous iliac arteriovenous fistula is a rare complication of these aneurysms with only 16 cases previously described. The diagnosis depends on a strong clinical suspicion and usually requires angiography for confirmation. We report a case in which CT with contrast medium showed clear findings of a spontaneous iliac arteriovenous fistula complicating rupture of an isolated iliac artery aneurysm. CT findings included: (1) iliac artery aneurysm, (2) vena caval dilatation, (3) rapid flow of contrast medium from the arterial side into the dilated inferior vena cava on dynamic scanning, (4) increased density of the inferior vena cava similar to that of the aorta caused by entry through the fistula of blood with a high concentration of iodinated contrast medium, and (5) the actual fistula connecting the two vessels.

Effect of heparin on adaptation of vein grafts to arterial circulation.

We studied the effect of heparin on wall thickening in balloon-injured carotid arteries and vein grafts in rabbits. Heparin (0.3 mg/kg of body weight/hour) reduced intimal cross-sectional area in balloon-injured carotid arteries at 2 weeks (0.20 +/- 0.05 mm2 vs. 0.05 +/- 0.02 mm2, p = 0.02). Autoradiography after a single pulse of tritiated thymidine revealed no labeling in the few intimal cells present in heparin-treated animals, whereas control smooth muscle cells (SMC) had a 10% labeling index. Heparin did not affect medial proliferation, suggesting that the decrease in intimal thickening was largely due to inhibition of SMC migration into the intima. Heparin caused a slight reduction in intimal cross-sectional area at 2 weeks in vein grafts (0.17 +/- 0.03 mm2 vs. 0.09 +/- 0.02 mm2, p = 0.03) but no significant reduction in wall thickness at any other time and no reduction in SMC proliferation rate (thymidine labeling index). DNA content per surface area or dry weight was the same in control and heparin-treated vein grafts at 4 weeks, implying that SMC content and the amount of matrix made by individual SMC was not affected. These data suggest that either SMC in veins are less susceptible to heparin than SMC in arteries, or the mechanism of thickening is substantially different. Heparin may not block all forms of SMC proliferation and may only be a weak inhibitor in processes that primarily are in response to changes in pressure.

Cerebromeningitis in immunosuppressed recipients of renal allografts.

The experience with cerebromeningitis in recipients of 769 renal allografts occurring over a 20-year period has been reviewed. Eighteen patients developed this complication; an incidence of 2.7%. Clinical manifestations were often subtle, although fever occurred almost universally. Primary risk factors included diabetes mellitus, use of high dose steroids both as maintenance immunosuppression and as treatment for acute rejection, and coincident infections or complications. The responsible organisms were fungi; the overall mortality rate 44%. By recognizing individual patient types who are at potential high risk for this complication, earlier diagnosis and more prompt and aggressive therapy has diminished the mortality dramatically in the last several years.