Effects of endothelial injury on the rate of thrombus organization in canine carotid arteries occluded with microcoils.

SUMMARY: Thrombus organization in canine carotid arteries occluded with platinum microcoils was studied to determine if endothelial injury created with a Xenon Chloride Excimer Laser (XEL) could acclerate endovascular fibrosis. Ten common carotid artery stumps were created in ten dogs. Each of four stumps were schematically divided into four longitudinally contiguous injury zones (thermal ablation injury, non-ablative injury, proximal and distal non-injury zones) to test the effects of ablative and non-ablative injury and to establish a set of internal controls that would account for proximity to circulating blood at the ostium of the occluded artery. Following XEL irradiation of the endothelium through an arteriotomy, each stump was embolized with microcoils. Four control stumps were subjected to sham laser procedures, and embolized in an identical fashion. Two additional stumps were embolized in the absence of sham surgery. Angiographic, gross and histologic analysis was performed after four weeks. Specimens of freshly clotted whole blood mixed with microcoils were used as an additional control. In irradiated stumps and non-irradiated stumps (sham and embolization only), angiography revealed no evidence of coil compaction or recanalization. In all irradiated stumps the thermal ablation zone contained fibrous tissue and neovascularity without unorganized thrombus. The other zones in the irradiated stumps were indistingnishable from each other and from all zones in the non-irradiated sham stumps, containing primarily unorganized thrombus. Stumps embolized in the absence of sham surgery were filled with material that was grossly and microscopically identical to specimens of freshly clotted whole blood containing microcoils. The results indicate that thermal ablation injury of the endothelium accelerates thrombus organization in canine carotid arteries occluded with platinum microcoils.

In vitro effects of transcatheter injection on structure, cell viability, and cell metabolism in fibroblast-impregnated alginate microspheres.

PURPOSE: To determine if microsphere-encapsulated cell preparations can be delivered through a microcatheter without compromising microsphere structure, cell viability, or metabolism. MATERIALS AND METHODS: Fibroblast-impregnated microspheres were fabricated by using 1.0% alginate and rabbit synovial fibroblasts. Fibroblast-impregnated alginate microspheres injected through microcatheters were analyzed in parallel with identical noninjected microspheres. The effects of transcatheter injection on structure and cell viability (percentage of viable cells per microsphere) were correlated with microsphere size. Structural effects were analyzed by using light microscopy, and 7-day percentage (ratio of live cells to dead cells) cell viability was assessed with confocal microscopy and fluorescent staining. In a second series of experiments, the metabolism of small microspheres was studied during a course of 7 days by using a spectrophotometric bioanalyzer. RESULTS: Transcatheter injection caused fracturing and/or fragmentation of large (800-1,000 microm) and medium (500-750 microm) microspheres, while small (250-400 microm) microspheres were structurally unaffected by transcatheter injection. Fracturing and fragmentation were associated with cell release from the alginate matrix. Although transcatheter injection reduced cell viability by 17%-23% in all size categories, it did not cause a detectable alteration in the rate of glucose metabolism. CONCLUSION: Transcatheter injection was physiologically well tolerated by fibroblasts encapsulated in alginate microspheres; however, when microsphere diameter exceeded the catheter diameter, fracturing and fragmentation of microspheres compromised the sequestration function of the microsphere vector.

Preliminary reports and the rates of publication of follow-up reports in peer-reviewed, indexed journals.

PURPOSE: To test the hypothesis that articles published as "preliminary" or "pilot" reports are followed by more definitive publications in only a minority of cases. METHOD: A survey of Medline was performed for reports published in 1992 in journals listed in the Abridged Index Medicus that had the word "preliminary" or "pilot" in the title. For identified reports, a Medline search of publications in 1992 through 1999 was performed, using lead author's name, second author's name, and senior (last) author's name, and at least one keyword based on the publication title. Preliminary and pilot publications were subdivided by type of study (controlled clinical study, case series, laboratory or nonclinical) and by the report of either positive or negative results. Rates of publication based on study design and publication bias were compared using the chi-square test for statistical significance. RESULTS: The rate of publication of follow-up reports within seven years of the initial publication was 27%. Follow-up studies of controlled clinical studies (40%) were published more frequently than were those of laboratory or nonclinical studies (31%) or case series (22%), but these differences were not significant (p >.10). There was no statistically significant difference in follow-up publication rates based on publication bias. CONCLUSION: Only 27% of studies published as preliminary or pilot reports were subsequently followed by a more definitive publication. While the words preliminary and pilot suggest that publication of further, refined work is pending, this is often not the case.

Timing of ICAM-I Expression in a Canine Model of Post-Haemorrhagic Cerebral Vasospasm.

SUMMARY: Temporal alterations in endothelial intercellular adhesion molecule I (ICAM-I) expression during the course of post-haemorrhagic cerebral vasospasm (PHCV) are correlated with angiographic and histologic changes in the canine basilar artery. Angiography was performed in six dogs to obtain baseline measurements of basilar artery diameter. In three dogs subarachnoid haemorrhage (SAH) was created by performing percutaneous puncture of the cisterna magna, and replacing 7 ml of cerebrospinal fluid with 7 ml of arterial blood. The remaining three dogs were used as controls. Daily angiography was performed on all dogs to determine the percent reduction in basilar artery diameter (%RBAD). One dog from each group was sacrificed after 24 hours. The remaining two dogs in each group were sacrificed after 48 hours. Each basilar artery was perfusion fixed and subjected to histologic, and immunohistochemical analysis. In the SAH group, the average %RBAD was 4 (+/- 3) at 24 hours, and 36 (+/- 1) at 48 hours. In the control group, the average %RBAD was - 1 (+/- 1) at 24 hours, and 0 (+/- 2) at 48 hours. Endothelial edema and endothelial expression of ICAM-I were found at 24 hours.At 48 hours post-SAH there was widespread endothelial desquamation, but no evidence of ICAM-I expression. In the control group, histology was normal and no ICAM-I expression was found at 24 or 48 hours. The results suggest that a brief window of therapeutic efficacy exists during the first postictal 24 hours where ICAM-I antagonists may be useful in suppressing the pathogenesis of PHCV.

Microsurgical anatomy of the artery of Adamkiewicz and its segmental artery.

OBJECT: The blood supply of the lower spinal cord is heavily dependent on the artery of Adamkiewicz, which characteristically originates from one of the thoracolumbar segmental arteries. The aforementioned artery is of enormous clinical, surgical, and radiological importance, and the goal of this study was to elucidate the course and branches of the segmental artery that gives rise to this important vessel. METHODS: In this cadaveric, microsurgical anatomical study, the authors investigate and describe the course and branches of the artery of Adamkiewicz and the segmental branch from which it ultimately originates. A review of the literature is provided. CONCLUSIONS: By documenting the microsurgical anatomy of these important vessels, this study facilitates an understanding of the anatomy that will aid in treatment planning for surgery of various lesions in this area.

Histologic and morphologic comparison of experimental aneurysms with human intracranial aneurysms.

PURPOSE: Vein pouch aneurysms are the most commonly created experimental lesions in neuroendovascular research. We sought to determine whether an experimental aneurysm that is derived from a pancreatic elastase-digested arterial sac (EDASA) models the histology and morphology of human cerebral aneurysms more accurately than the vein pouch aneurysm does. METHODS: EDASAs were created in the common carotid arteries of four rabbits, and vein pouch aneurysms were created in the common carotid arteries of four pigs. Five recently ruptured human cerebral aneurysms were obtained at autopsy. Identical histologic preparations were made for all specimens, and a vascular pathologist performed blinded histologic analyses. Morphologic dimensions were measured with a micrometer at 40-fold magnification. RESULTS: In each human cerebral aneurysm, there was complete absence of internal elastic lamina and tunica media, and none showed evidence of mural inflammation or neointimal proliferation. Average wall thickness was 51 microm. All vein pouch aneurysms had a well-developed internal elastic lamina and tunica media, and all exhibited profound inflammation and neointimal proliferation. Average wall thickness was 290 microm. EDASAs were devoid of internal elastic lamina, their tunica medias were mildly atrophic, and the sac walls contained only mild inflammation and neointimal proliferation. Average wall thickness was 46 microm. CONCLUSIONS: EDASAs model the morphologic and histologic characteristics of human cerebral aneurysms more accurately than vein pouch aneurysms do.

Histologic effects of collagen-filled interlocking detachable coils in the ablation of experimental aneurysms in swine.

PURPOSE: To assess the histologic changes produced by platinum microcoils with an inner core of cross-linked bovine collagen in experimentally induced aneurysms in swine, and to assess the feasibility of the system for the delivery of the collagen. METHODS: Bilateral pouch aneurysms were created in the side wall of the common carotid artery in seven barnyard pigs. Eight aneurysms were treated with coils designed with an interlocking detachment mechanism: in four of these, the coils had an inner core of collagen; in the other four, the platinum microcoils had a similar design but without the collagen mandrel. The packing density of the coils within the aneurysm was approximately the same for both types of coils. The other six aneurysms were left untreated and served as controls. Angiograms were obtained at the time of treatment (2 weeks after the aneurysms were created) and at 1, 4, and 8 weeks after treatment. All animals were killed 8 weeks after the treatment (10 weeks after the aneurysms were created). Arteries and aneurysms were resected en bloc and fixed for histopathologic study. RESULTS: The interlocking detachment mechanism worked well. Little difference was noted between the two types of coils in their ability to effect complete aneurysmal thrombosis (three of four aneurysms treated with collagen-core coils and two of four aneurysms treated with conventional coils). The collagen-core coils stimulated new collagen formation in areas proximal to the coils, and more fibroblasts were noted near the collagen-core coils than near the conventional coils. CONCLUSION: Local fibroblast proliferation and collagen production were stimulated by heterologous cross-linked collagen embedded in micro-coils in this experimental model. Such biologic stimulation holds promise for improving the endovascular cure rate of aneurysms in humans.

Treatment of experimental aneurysms using collagen-coated microcoils.

Endovascular treatment of certain surgically difficult aneurysms is currently performed using fibered microcoils or electrolytically detachable microcoils to obliterate these lesions by forming an intra-aneurysmal thrombus. Unfortunately, this treatment option results in a significant incidence of incomplete obliteration of treated aneurysms. A thrombus can recanalize, resulting in further aneurysm growth and subsequent rupture. Nineteen aneurysms were surgically created in 10 pigs using jugular venous pouches. The aneurysms were allowed to mature for periods of 7 days to as long as 11 weeks prior to embolization. Fourteen remained patent for embolization. The aneurysms were then embolized (9 with collagen-coated microcoils, 5 with dacron-fibered platinum microcoils). Follow-up angiograms were obtained prior to sacrifice at 1, 3, 6, 9, and 12 weeks postembolization, and the embolized aneurysms and parent vessels were harvested for histopathological studies. The current study was designed to evaluate the potential efficacy of collagen-coated microcoils in providing an enduring therapy for aneurysms by comparing this new embolic device with the standard dacron-fibered platinum microcoils in a swine common carotid artery side wall aneurysm model. The aneurysms treated with collagen microcoils were completely obliterated with a collagen-rich fibrous scar with no histological evidence of residual thrombus or recanalization. Additionally, after treatment of experimental aneurysms with collagen microcoils, re-endothelialization across the former aneurysm neck was seen. In contrast, aneurysms embolized with dacron-fibered microcoils contained persistent thrombus surrounded by a relatively immature scar with residual aneurysmal lumen and lack of endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)