Elastase-induced saccular aneurysms in rabbits: comparison of geometric features with those of human aneurysms.

BACKGROUND AND PURPOSE: The development of more effective intracranial aneurysm therapy depends on the ability to test various intravascular occlusion devices and techniques in preclinical animal models. This requires the creation of experimental aneurysms, which, ideally, should mimic the size and geometric features of human intracranial aneurysms. The purpose of this study was to characterize the morphologic features of elastase-induced saccular aneurysms in rabbits to determine whether the morphology of such aneurysms mimics that of human intracranial aneurysms. METHODS: Elastase-induced saccular aneurysms were created in 40 New Zealand white rabbits. Intravenous digital subtraction angiography was performed 14 days after surgery. Relative to an external sizing device, the following dimensions were determined: aneurysm dome (height and width), aneurysm neck diameter, and parent artery diameter. Based on maximal diameter, aneurysms were categorized as small (2.0-4.9 mm), medium-sized (5.0-9.9 mm), or large (10-16 mm), and as narrow-necked (<4.0 mm neck width) or wide-necked (>4.0 mm neck width). Mean dome-neck ratio was calculated and compared with that of human aneurysms. RESULTS: All aneurysm cavities were angiographically patent. Widths of the cavities ranged from 2.5 to 7.1 mm (mean, 4.1 +/- 1.2 mm); heights ranged from 3.0 to 15.6 mm (mean, 8.8 +/- 2.6 mm). Three (7.5%) of 40 aneurysms were small, 20 (50%) were medium-sized, and 17 (42.5%) were large. Twenty-two (55%) of 40 aneurysms were small-necked, and 18 (45%) were wide-necked. Mean dome-neck ratio was 1.13 +/- 0.54. Mean parent artery diameter was 4.3 +/- 1.4 mm. CONCLUSION: Saccular aneurysms of sizes similar to that of human intracranial aneurysms were reliably created using a simple method of vessel ligation and elastase injury. Neck sizes varied with both large and small-necked aneurysms created.

Dr. Gary J. Becker young investigator award: comparison of small-diameter type 1 collagen stent-grafts and PTFE stent-grafts in a canine model--work in progress.

PURPOSE: To report an in-progress experiment in a canine model in which two types of small-diameter stent-grafts-one constructed of polytetrafluoroethylene (PTFE) and the other of a new, type 1 collagen material-were compared regarding vessel patency, intimal hyperplasia formation, and tissue reaction. MATERIALS AND METHODS: Six mongrel dogs weighing 30-35 kg were used. Stent-grafts of 4-mm diameter and 20-mm length were constructed with use of balloon-expandable stainless-steel stents wrapped with either PTFE or a new type 1 collagen graft. Stent-grafts were placed in deep femoral arteries bilaterally (PTFE on one side, collagen on the other). Animals were followed for 2 weeks (n = 2), 6 weeks (n = 2), or 12 weeks (n = 2). Percent stenosis based on angiographic findings as well as thickness and area of neointimal hyperplasia were compared at each time point and compared with use of the Student t test. RESULTS: All devices were patent in the immediate postimplantation period. Five of six collagen stent-grafts and five of six PTFE implants were patent at follow-up. In-stent stenosis was undetectable angiographically in all five patent collagen stent-grafts. All five patent PTFE stent-grafts showed demonstrable in-stent stenosis (10%-60%), indicating a trend toward improved patency in collagen stent-grafts versus PTFE stent-grafts (P = .07). Neointimal hyperplasia was absent at 2 weeks in the collagen stent-grafts. Neointimal thickness increased to a maximum of 360 microm at 12 weeks in the collagen stent-grafts. For PTFE stent-grafts, neointimal hyperplasia was present in all samples and reached a maximum of 770 microm at 12 weeks (P = .03). CONCLUSIONS: Even in small-diameter vessels, type 1 collagen stent-grafts demonstrate excellent patency rates and favorable histologic findings. The type 1 collagen stent-graft technology merits further developmental efforts in preclinical models.

Serial angiography in an elastase-induced aneurysm model in rabbits: evidence for progressive aneurysm enlargement after creation.

BACKGROUND AND PURPOSE: Among the several reports of elastase-induced aneurysm models, only the rabbit common carotid artery (CCA) model has been used for testing endovascular occlusion devices. Our purpose was to study the growth characteristics of an elastase-induced aneurysm model in rabbits for the purpose of determining whether delayed aneurysm enlargement occurs after creation. METHODS: Nine New Zealand White rabbits (3-4 kg) were used in this study. All study animals underwent surgery to isolate the right CCA. In three control animals, the lumen was incubated with saline and iodinated contrast material for 20 minutes. In six test animals, the lumen of the CCA was incubated with porcine elastase for 20 minutes. In all study animals, the distal right CCA was ligated. IV digital subtraction angiography was performed on postprocedural days 3, 5, 7, 14, 28, 35, 56, 84, and 112. Using an external sizing reference, the width and height of patent arterial segments at the right CCA origin were measured by two observers. For test animals, aneurysm dimensions were compared between early and late time points by using the Student's t test. RESULTS: In the control (no elastase) animals, slitlike cavities at the origin of the right CCA decreased in size over time to become nearly obliterated by 21 days. Conversely, a short segment of the proximal CCA remained widely patent in all six test animals. With the exception of a single time point in one test animal, all "aneurysm" cavities in the test animals were dilated as compared with the normal diameter of the CCA. On day 3 after surgery, the mean width and height of the aneurysm cavities in the test animals were 3.2 +/- 0.6 and 6.0 +/- 1.3 mm, respectively. Compared with dimensions at day 3, aneurysms in test animals were larger at day 14, with mean width and height of 4.1 +/- 1.7 and 8.3 +/- 1.9 mm, respectively (P =.02). Aneurysms in test animals had increased further at 21 days compared with 14 days (P =.01). Compared with measurements obtained at 21 days, dimensions remained essentially unchanged at 28 and 35 days. Thirty-five days after surgery, mean width and height were 5.0 +/- 0.9 and 10.0 +/- 2.2 mm, respectively. Follow-up imaging performed < or = 4 months after aneurysm creation showed no further change in aneurysm dimensions. CONCLUSION: Elastase incubation and vessel ligation results in patent aneurysmally dilated arterial segments at the origin of the right CCA in rabbits. These aneurysms show progressive increases in diameter over time, finally stabilizing at approximately 1 month. Our data, which show early progressive aneurysm enlargement, suggest that this model may be used for the study of systemic therapies aimed at diminishing aneurysm rest regrowth and also indicate that embolization of these model aneurysms should be delayed at least 21 days after aneurysm creation.

Endovascular treatment of experimental aneurysms by use of biologically modified embolic devices: coil-mediated intraaneurysmal delivery of fibroblast tissue allografts.

BACKGROUND AND PURPOSE: Our long-term goal is to improve intraaneurysmal fibrosis after aneurysm embolization, by implanting exogenous fibroblasts, using platinum coils. For the current project, we tested two hypotheses: 1) that exogenous, fluorescence-labeled rabbit fibroblast allografts remained viable and proliferated within rabbit carotid arteries, and 2) that these fibroblast allografts could be reliably implanted into experimental aneurysms by use of platinum coils. METHODS: Part 1. New Zealand White rabbit synovial fibroblasts obtained from a commercial vender were labeled with a fluorescent membrane marker. The common carotid arteries of New Zealand White rabbits were surgically exposed, ligated proximally and distally, and entered with 22-g angiocatheters. Through the angiocatheter we injected either phosphate-buffered saline-containing fluorescence-labeled fibroblasts (treatment vessels) or saline only (control vessels). The wounds were closed, and the subjects were kept alive for various time points up to 2 weeks. After sacrifice, the carotid artery segments were resected, processed for frozen-section histologic examination, and evaluated using epifluorescent microscopy and hematoxylin and eosin staining. Cell viability and proliferation were determined by comparing the treatment versus control vessels. Part 2. A) Fluorescence-labeled cells were grown in culture on platinum coils, which were then exposed to systemic arterial flow in the rabbit thoracic aorta for various lengths of time up to 40 minutes. The coil segments were then examined using fluorescent microscopy and the presence and relative amount of cells remaining on the coil were documented. B) Experimental aneurysms in rabbits were embolized with control platinum coils (n = 9) and platinum coils bearing rabbit synovial fibroblasts that were grown onto the coils in culture prior to implantation (n = 9). Subjects were sacrificed 3, 7, and 14 days after coil implantation. Histologic samples were studied to assess the presence or absence of nucleated cells within and around coil winds in order to determine whether fibroblasts had been successfully implanted into aneurysms. Data were evaluated using the chi-square test for statistical significance. RESULTS: Part 1. Fluorescence-labeled cells were examined in the treatment carotid artery segments and results were recorded at all time intervals. The treatment vessel segments showed evidence of progressive cellular proliferation, leading to complete vessel fibrosis at 2 weeks. Conversely, control vessel segments were filled predominately with unorganized thrombus at each time interval. Part 2. A) Numerous labeled fibroblasts remained adherent to the coil despite prolonged exposure to systemic arterial flow. B) Fibroblasts were seen adjacent to or within the central lumen of coils in eight (88%) of nine aneurysms treated with cell-bearing coils. Nucleated cells were not present in any of the nine control coil subjects. This represented a statistically significant difference (P < .001). CONCLUSION: Fibroblast allografts remain viable and proliferate in the vascular space in rabbits. Furthermore, these same fibroblasts, after seeding onto platinum coils in culture, remain protected within the lumen of the coils and are retained within the coil lumen even after prolonged exposure to arterial blood flow. Coils can be used to deliver viable fibroblasts directly into experimental aneurysms successfully. These findings indicate that coil-mediated cell implantation is feasible and may be a potential method of increasing the biological activity of embolic coils.

Value of bone scan imaging in predicting pain relief from percutaneous vertebroplasty in osteoporotic vertebral fractures.

BACKGROUND AND PURPOSE: Patient selection for percutaneous vertebroplasty is often complicated by the presence of multiple fractures or non-localizing pain. Our purpose was to determine whether increased activity revealed by bone scan imaging is predictive of a positive clinical response to percutaneous vertebroplasty. METHODS: A retrospective chart review conducted at our institution yielded 28 vertebroplasty treatment sessions that had been performed after obtaining bone scan imaging for painful, osteoporotic compression fractures in 27 patients. Thirty-five compression fractures were treated during these 28 treatment sessions. In all cases, increased activity was revealed by bone scan imaging before treatment with vertebroplasty. Positive outcome was defined as subjective decrease in pain severity and/or increased level of patient mobility. RESULTS: Subjective pain relief was noted in 26 (93%) of 28 treatment sessions. In 14 (100%) of 14 cases with quantifiable pain levels, pain improved at least 3 points on a 10-point scale (range of improvement, 3-10 points; mean improvement, 7.4 points). Among the remaining 14 treatment sessions in which patients were unable or unwilling to quantify pain severity, the pain relief was described as complete or excellent pain relief in 11 (78%) of 14 cases. In 14 (100%) of 14 cases for which semiquantitative assessment of mobility was available, mobility improved at least one level (5-point graded scale; range of improvement, 1-4 points; mean improvement, 1.7 points). CONCLUSIONS: Increased activity revealed by bone scan imaging is highly predictive of positive clinical response to percutaneous vertebroplasty.

1999 ARRS Executive Council Award. Creation of saccular aneurysms in the rabbit: a model suitable for testing endovascular devices. American Roentgen Ray Society.

OBJECTIVE: This study developed an animal model of intracranial aneurysms suitable for evaluating emerging endovascular devices for aneurysmal therapy. We characterized the short-, medium-, and long-term attributes of this endovascular technique for saccular aneurysmal creation in the rabbit. MATERIALS AND METHODS: The right common carotid artery was surgically exposed in nine New Zealand white rabbits. Using endovascular techniques, we occluded the origin of the right common carotid artery with a pliable balloon. Elastase was incubated endoluminally in the proximal common carotid artery above the balloon. The common carotid artery was ligated distally. Animals were studied angiographically and sacrificed at 2 weeks (n = 3), 10 weeks (n = 3), and 24 weeks (n = 3) after aneurysm creation. Histology was obtained. RESULTS: Saccular aneurysms formed in eight of the nine rabbits. The aneurysm projected from the apex of an approximately 90 degree curve of the parent vessel, the brachiocephalic artery. Mean aneurysm diameter was 4.5 mm (SD, 1.2 mm), and mean height was 7.5 mm (SD, 1.6 mm). All samples showed thinned elastic lamina and no evidence of inflammation. In four of eight aneurysms, unorganized thrombus was present in the dome of the aneurysm. CONCLUSION: Arterial aneurysms with intact endothelium and deficient elastic lamina were reliably created in an area of high shear stress in New Zealand white rabbits. Three of these aneurysms remained patent for at least 6 months. We found a simple procedure that can be readily applied to the testing of new endovascular devices for a reliable creation of aneurysms in rabbits.

Defining the cost of educating undergraduate medical students at the University of Virginia.

PURPOSE: To develop a model for calculating the cost of a four-year undergraduate medical education at the University of Virginia School of Medicine (UVA) in 1994-95. METHOD: All data were based on faculty contact hours (FCHs), the primary driver of cost. (An FCH was an hour during which a faculty member was actively teaching.) First- and second-year data were derived from a published curriculum schedule. Third-year data were derived from hours spent in each clerkship and a series of calculations to assess direct teaching time in each clerkship accurately. Fourth-year data were modeled on an artificial but typical program consisting of the required clerkship in neurology, a two-day course in advanced cardiac life support, and seven elective blocks; electives were chosen based on relative overall popularity. The number of full-time-equivalent (FTE) faculty required was calculated. The salary costs of UVA full-time faculty were calculated. Other total direct costs, including the costs of support and administrative services as well as the costs of the educational contributions of housestaff and contract faculty, were calculated. The overall cost, including direct and indirect costs, was calculated. An average of 139 students per year was assumed. RESULTS: The total number of FCHs was just under 100,000. The number of FTE faculty required was 223. UVA faculty salary and fringe benefits totaled $29,400,000. The costs of support and administrative services totaled $4,100,000; the costs of housestaff and contract faculty totaled $2,300,000. The overall educational costs totaled $49,600,000. CONCLUSION: The overall cost of a four-year medical education at UVA was $357,000 per student. Although the process of calculating this cost was complex and, at times, based on assumptions open to debate, the model developed can be applied to any medical education setting.

Measures of knowledge and attitude toward preventive cardiology.

In this paper, the authors describe the development and validation of an inventory of preventive cardiology at the University of Virginia. The inventory contains two instruments designed to measure medical students' preinstructional and postinstructional knowledge of and attitude toward preventive cardiology. The knowledge test subscales provide unique and significant information about knowledge in preventive cardiology and can discriminate among groups differing in level of instruction and expertise in preventive cardiology. The attitude survey provides information about two attitude factors: cardiovascular disease prevention and cardiovascular disease research priorities. In the study reported here, attitudes appeared not to differ among groups of students with different preventive cardiology instructional levels and expertise. Both instruments were demonstrated to be useful measures of medical students' knowledge and attitudes concerning preventive cardiology educational programs.

Perinatal outreach education. A continuation strategy for a basic program.

The Perinatal Continuing Education Program consists of a nine-month intervention with community hospital nurses, physicians, and support personnel. Components include a hospital self-inventory of resources, coordination by community hospital staff, a skills workshop, and self-instructional books. This article outlines a follow-up strategy to the basic program and describes changes in community hospital knowledge and care practices that occur between programs. The follow-up program presented includes a modified coordinators' workshop, identification of updated self-instructional materials for careful study by past participants, and a self-survey of "recommended routines" intended to facilitate change in hospital policies. Otherwise, except for the deletion of the resources inventory, the follow-up program is similar to the basic program. Testing of participants and detailed review of 1435 hospital charts at sequential time periods revealed a decline in mean knowledge scores between programs, higher scores by new participants before follow-up when compared to pre-basic program, a plateau of patient care quality between programs, and a further improvement in patient care quality after the follow-up program. We conclude that a follow-up program is best accepted after three years but that timing is not critical. Evaluation measures suggest that new knowledge and care practices become institutionalized as a result of this program and that altered care practices are not simply a result of improved performance by individuals.