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Biomedical subjects

Debra A Lewis

Publications and source records attributed to Debra A Lewis.

10 recordsLinked to original sources

Endovascular treatment of experimental aneurysms by use of fibroblast-coated platinum coils: an angiographic and histopathologic study.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether implanting exogenous fibroblasts on platinum coils could enhance intra-aneurysmal fibrosis. Hypotheses included: (1) fibroblast-coated (FBC) platinum coils can improve angiographic results after embolization; and (2) FBC platinum coils can accelerate histological healing of embolized aneurysms. METHODS: Experimental aneurysms in rabbits were embolized with control platinum coils (n=18) or FBC coils (n=18). Subjects were euthanized at 14 days, 1 month, 3 months and 6 months after implantation. Digital subtraction angiography was used to evaluate stability after embolization. Histological samples were examined with a grading system (range, 0 to 12) based on neck and dome healing. RESULTS: Histology total scores and fibrosis ratio at 14 days were significantly greater in the FBC coil group compared with controls (6.6+/-1.9 versus 2.5+/-1.1, 1.2+/-0.6% versus 0.2+/-0.3%, respectively; P=0.0090). Cavities embolized with FBC coils showed cellular proliferation and thrombus organization, with an endothelialized membrane bridging the neck. There were no differences between groups in the later timepoints. The FBC coil group showed radiographic stability in 11 (61%) cases, coil compaction in 2 (11%) cases, and progressive occlusion in 5 (28%) cases. No progressive occlusion was seen in controls; 3 (17%) of 18 control cases exhibited coil compaction (P=0.0546). CONCLUSIONS: FBC coils can accelerate early histological healing compared with control coils in the rabbit aneurysm model.

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Modified technique to create morphologically reproducible elastase-induced aneurysms in rabbits.

INTRODUCTION: The purpose of this study was to create morphologically reproducible elastase-induced model aneurysms in rabbits. METHODS: We created 120 elastase-induced aneurysms in rabbits using two different methods: the standard technique (group 1, n=62) and a modified technique (group 2, n=58). In the standard technique a small cutdown with a focal area of exposure of the mid-right common carotid artery (RCCA) was employed, while in the modified technique the RCCA was completely exposed to its origin. We measured aneurysm sizes (neck diameter, width and height) in the two groups. The aneurysm sizes were compared between the two groups using Student's t test, and the standard deviations of the aneurysm sizes were compared between the groups using the F test. RESULTS: The mean aneurysm neck size, width and height in group 1 were 3.4+/-1.2 mm, 3.8+/-1.0 mm and 8.0+/-1.7 mm, respectively, and in group 2, were 3.2+/-0.9 mm, 3.7+/-0.6 mm and 9.1+/-1.8 mm, respectively. The differences in mean aneurysm neck and width between the two groups were not significant (P>0.05). However, there were significant differences in the standard deviation of these two parameters between the two groups (P<0.05 and P<0.01, respectively). The mean aneurysm height in group 2 was larger than in group 1 (P<0.001), but no significant difference in the standard deviation of this parameter between the two groups was found (P>0.05). CONCLUSION: The results indicate that more consistent aneurysm diameters can be created using the modified technique.

Animals↗

Treatment with raloxifene and 17beta-estradiol differentially modulates nitric oxide and prostanoids in venous endothelium and platelets of ovariectomized pigs.

Oral treatment with raloxifene, a synthetic estrogen receptor modulator (SERM), or 17beta-estradiol (E2) increases risk for venous thrombosis in women. Acute application of either substance releases endothelium-derived factors from isolated femoral veins but it is not known how their chronic use affects venous functions or the interaction of platelets with veins. This study tested the hypothesis that treatment of ovariectomized animals with oral raloxifene or E2 would increase release of proaggregatory factors from venous endothelium and platelets. Ovariectomized (OVX) pigs were either untreated or treated with oral raloxifene (60 mg/day) or E2 (2 mg/day) for 4 weeks. Plasma concentrations of nitric oxide were comparable in both treatment groups and greater than in OVX pigs. Ratio of plasma thromboxane to prostacyclin was twofold greater in raloxifene compared to E2-treated pigs. In isolated femoral veins, NG-monomethyl-L-arginine (L-NMMA; 10(-4) M) augmented endothelium-dependent relaxations to adenosine diphosphate in veins from E2-treated pigs but inhibited relaxations in veins from raloxifene-treated pigs. Addition of indomethacin (10(-5) M) reversed these effects. Endothelium-dependent relaxations to thrombin were inhibited by L-NMMA only in OVX and raloxifene-treated pigs. Autologous platelets contracted veins in all groups; the magnitude of contractions depended upon the number of platelets and existing tone. Basal release of thromboxane from platelets was greatest in raloxifene compared to OVX or E2-treated pigs. Raloxifene treatment compared to E2 increased production of contractile and proaggregatory prostanoids from venous endothelium and platelets. These differences, if found in humans, may contribute to varying degrees of thrombotic risk with the SERM compared to the natural hormone.

Animals↗

Vascular anatomic variation in rabbits.

PURPOSE: To explore the vascular anatomic variation along the aortic arch in New Zealand White rabbits with the goal of highlighting potential anatomic configurations that might be encountered in the performance of preclinical endovascular research in rabbits. MATERIALS AND METHODS: Digital subtraction angiography images of the brachiocephalic artery (BCA) and aortic arch in New Zealand White rabbits were obtained after creation of elastase-induced aneurysms at the origin of the right common carotid artery (RCCA) in 214 animals. The patterns of origin of the RCCA and left common carotid artery (LCCA), right subclavian artery (RSCA) and left subclavian artery (LSCA), and right vertebral artery (RVA) and left vertebral artery (LVA) were analyzed. RESULTS: Five predominant variations of vessel origin were identified. In 200 of 214 cases (93%), the LCCA originated from the bifurcation of the BCA and aorta. In eight cases (4%), the LCCA directly originated from the aorta. In two cases (1%), the LCCA originated from the BCA. Aberrant RSCA anatomy in which the RSCA originated from the aortic arch instead of the BCA was found in three cases (1.5%). In a single case (0.5%), aberrant RSCA anatomy with the RVA originating from the BCA was encountered. CONCLUSIONS: Anatomic variation of the BCA in New Zealand White rabbits is similar to that seen in humans. Understanding of the normal and variant anatomy of the rabbit will aid investigators who use the rabbit model for endovascular research.

Angiography, Digital Subtraction↗

Intra-venous digital subtraction angiography: an alternative method to intra-arterial digital subtraction angiography for experimental aneurysm imaging.

Conventional intra-arterial digital subtraction angiography (IADSA), which necessitates surgical exposure and ligation of the femoral artery, is an invasive and expensive method of evaluation for experimental elastase-induced aneurysms in rabbits. The purpose of this study was to examine and validate intra-venous digital subtraction angiography (IVDSA) as an alternative to IADSA by comparing their diagnostic accuracies. We performed both IVDSA and IADSA for 24 elastase-induced saccular aneurysms in a rabbit model, 1 month following creation. Aneurysm sizes (neck, width and height) from both the IVDSA and IADSA procedures were evaluated and measured. Comparison of the aneurysm sizes between IVDSA and IADSA were performed with the Wilcoxon paired signed-rank test. All the aneurysms were seen clearly in both the IVDSA and IADSA techniques. Mean sizes of the IVDSA aneurysm neck, width and height were 3.41 +/- 0.80 mm, 3.61 +/- 0.93 mm and 8.07 +/- 2.11 mm, respectively. Mean sizes of the IADSA aneurysm neck, width and height were 3.43 +/- 0.80 mm, 3.66 +/- 0.92 mm and 8.16 +/- 2.25 mm, respectively. No significant difference was found in the sizes of the aneurysm neck, width and height between the two groups (P = 0.311, P = 0.086 and P = 0.258, respectively). IVDSA appears to be an alternative method for evaluating elastase-induced aneurysms in rabbits.

Angiography, Digital Subtraction↗

Angiographic and histologic analysis of experimental aneurysms embolized with platinum coils, Matrix, and HydroCoil.

BACKGROUND AND PURPOSE: A report directly comparing platinum coils, Matrix coils, and HydroCoils in a single animal model does not currently exist. We evaluated and compared the performance of these three products in the embolization of experimental aneurysms. METHODS: Thirty-three elastase-induced saccular aneurysms were created in rabbits. Aneurysms were embolized with Matrix coils (n = 15), HydroCoils (n = 9), or platinum coils (n = 9). The groups were compared with respect to the following parameters: aneurysm size, procedure duration, number and total length of devices deposited, angiographic occlusion score, and volumetric occlusion percentage. Follow-up angiographic and histologic features at 2, 6, and 10 weeks after embolization were analyzed. Groups were compared by using analysis of variance and chi2 tests. RESULTS: No significant differences were found among groups regarding aneurysm size, total device length, initial angiographic occlusion score, or procedure time. The mean number of devices for Matrix subjects was less than that for platinum coils (P = .02) and HydroCoil (P = .03). Volumetric occlusion for HydroCoil (76%) was significantly greater (P < .0001) than both platinum coils (31%) and Matrix (23%). Angiographic durability was significantly increased in the HydroCoil group compared with Matrix (P = .03). Coil compaction was found more frequently in the Matrix group (five cases, 33%) than the HydroCoil (no cases, 0%), or platinum coil groups (two cases, 22%). The Matrix group showed greater tissue reaction compared with platinum coils (P < .05). CONCLUSION: In the rabbit model, the use of HydroCoils results in improved long-term occlusion rates compared with Matrix and platinum coils. The Matrix group showed an increase in inflammation and coil compaction compared with HydroCoils and platinum coils.

Animals↗

Modified histologic technique for processing metallic coil-bearing tissue.

We developed a modified paraffin-embedding histologic technique for processing metallic coil-bearing aneurysm tissues. This modified technique was successfully employed for processing platinum coil-bearing tissue for 30 rabbit aneurysms and 6 swine aneurysms. This technique for sectioning coil-bearing aneurysms resulted in little or no tissue distortion and permitted good preservation of morphology and application of multiple advanced staining techniques. This technique is considered beneficial for studying the molecular mechanisms of aneurysm healing after coiling.

Animals↗

Can neck size in elastase-induced aneurysms be controlled? A prospective study.

BACKGROUND AND PURPOSE: An earlier retrospective study indicated that the neck size of elastase-induced aneurysms could be controlled by adjusting the position of the inflated balloon. We report the current prospective study to confirm our previous work. METHODS: Ninety elastase-induced aneurysms were created in rabbits. Group 1 (n = 62) included cases in which the occlusion balloon resided low, completely within the brachiocephalic/subclavian arteries. Group 2 (n = 28) included cases in which the balloon resided high, within both the common carotid artery and brachiocephalic/subclavian arteries. Follow-up digital subtraction angiography was performed. The aneurysm sizes were measured and compared between groups. The Student t test and the Fisher exact test were used for statistical analysis. RESULTS: The mean aneurysm neck diameter and width for group 1 was significantly larger than that of group 2 (3.4 +/- 1.2 and 2.3 +/- 0.9 mm, P < .001; 3.8 +/- 1.0 and 3.3 +/- 0.9 mm, P < .05, respectively). The proportion of wide-necked aneurysms in group 1 was significantly larger than that in group 2 (29% vs 4%; P < .005). Mean dome-to-neck ratios were 1.2 +/- 0.4 and 1.7 +/- 0.7 for groups 1 and 2 (P < .005). There was no significant difference in aneurysm height between groups 1 and 2 (8.0 +/- 1.7 and 7.5 +/- 2.2 mm; P > .05). CONCLUSION: The neck size of elastase-induced aneurysm models in rabbits can be controlled by adjusting the position of the inflated balloon.

Angiography, Digital Subtraction↗

Species characterization of plasma nitrite/nitrate (NOx) concentration.

Experiments were designed to detect and determine differences between nitrite/nitrate concentration ([NOx]) in plasma across 15 species selected from seven classes of vertebrates. Blood collected in syringes was placed immediately into ethylenediaminetetraacetic acid (EDTA)-containing tubes and was centrifuged. Plasma [NOx] was determined by measurement of chemiluminescence. Across classes of vertebrates, baseline plasma [NOx] ranged from 0.6 to 171.3 nmol/ml. Mean +/- SD plasma [NOx] was highest in a fresh-water, jawless fish (lamprey, 95.5 +/- 9.1 nmol/ml) and lowest in a saltwater cartilaginous fish (skates, 1.1 +/- 0.4 nmol/ml). Both amphibians tested had a wide range in plasma [NOx], which was explained partly by temporal changes during the year. Within the mammalian class, plasma [NOx] ranged from 3.8 to 43.2 nmol/ml. Results of this study indicate that NO is detectable in plasma of all classes of vertebrates and that baseline concentration varies among species.

Animals↗

Histopathologic and immunohistochemical comparison of human, rabbit, and swine aneurysms embolized with platinum coils.

BACKGROUND AND PURPOSE: The purpose of this study was to clarify the cellular mechanisms of aneurysmal healing by comparing histologic and immunohistochemical findings in experimental rabbit and swine aneurysms to a human aneurysm embolized with platinum coils. METHODS: Swine sidewall aneurysms (n = 5, harvested at 12 weeks) and elastase-induced rabbit aneurysms (n = 6, harvested at 24 weeks) were created and embolized. A single human aneurysm, embolized 6 years before death, was harvested following autopsy. All specimens were processed by using a modified paraffin embedding technique. Tissue was sectioned and stained with hematoxylin and eosin and Masson trichrome. Immunohistochemistry and immunofluorescence were performed with multiple antibodies, including alpha smooth muscle actin, myosin heavy chain, desmin, vimentin, and CD31. RESULTS: The human aneurysm's dome was filled with loose, hypocellular, amorphous tissue. The aneurysm's neck was completely covered with a thin layer of hypocellular tissue. Collagen and myofibroblasts were sparse in both the dome and neck. Rabbit aneurysms' domes were also filled with a loose, hypocellular tissue, amorphous matrix. In 5 of 6 aneurysms, a thin layer of hypocellular tissue ran along the neck. Collagen and myofibroblasts were sparse in the dome. Swine aneurysms were filled with densely infiltrated tissue, including chronic inflammatory tissue and extensive, attenuated collagen fiber bundles associated with myofibroblasts. Thick layers of myofibroblasts entirely bridged the necks. CONCLUSIONS: Absence of collagen deposition and scant myofibroblastic reaction to platinum coil embolization are seen in the rabbit model but not in swine aneurysms. The elastase-induced aneurysm model in rabbits is more suitable than sidewall swine aneurysms for testing of modified devices aimed at improving intra-aneurysmal fibrosis.

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