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Establishment of a rat and guinea pig aortic interposition graft model reveals model-specific patterns of intimal hyperplasia.

ABSTRACT: Although the aortic interposition bypass model has been widely used to evaluate biomaterials for bypass grafting, there is no comprehensive description of the procedure or of the distribution of intimal hyperplasia that results. The objectives of this study were to (1) review and summarize approaches of aortic interposition grafting in animal models, (2) determine the pertinent anatomy for this procedure, (3) validate this model in the rat and guinea pig, and (4) compare the distribution of intimal hyperplasia that develops in each species.A literature search was performed in PubMed from 1980 to the present to analyze the use of anesthesia, anticoagulation, antiplatelet agents, graft material, suture, and anastomotic techniques. Using 10-week-old male Sprague-Dawley rats and Hartley guinea pigs, we established pertinent aortic anatomy, developed comparable models, and assessed complications for each model. At 30 days, the graft and associated aorta were explanted, intimal formation was assessed morphometrically, and cellularity was assessed via nuclear counting.We reviewed 30 articles and summarized the pertinent procedural findings. Upon establishing both animal models, key anatomic differences between the species that affect this model were noted. Guinea pigs have a much larger cecum, increased retroperitoneal fat, and lack the iliolumbar vessels compared with the rat. Surgical outcomes for the rat model included a 53% technical success rate and a 32% technical error rate. Surgical outcomes for the guinea pig model included a 69% technical success rate and a 31% technical error rate. These two species demonstrated unique distribution of intimal hyperplasia at 30 days. Intimal hyperplasia in the rat model was greatest at two areas, the proximal graft (5400 ?m2; P < .001) and distal graft (2800 ?m2; P < .04), whereas the guinea pig model developed similar intimal hyperplasia throughout the graft (4500-5100 ?m2; P < .01).In this report, we summarize the literature on the aortic interposition graft model, present a detailed description of the anatomy and aortic interposition graft procedure in the rat and guinea pig, and describe a unique distribution of intimal formation that results in both species. This information will be helpful when designing studies to evaluate novel graft materials in the future.

SUBMITTER: Gregory EK

PROVIDER: S-EPMC4939129 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Establishment of a rat and guinea pig aortic interposition graft model reveals model-specific patterns of intimal hyperplasia.

Gregory Elaine K EK Vercammen Janet M JM Flynn Megan E ME Kibbe Melina R MR

Journal of vascular surgery 20160109 6

<h4>Objective</h4>Although the aortic interposition bypass model has been widely used to evaluate biomaterials for bypass grafting, there is no comprehensive description of the procedure or of the distribution of intimal hyperplasia that results. The objectives of this study were to (1) review and summarize approaches of aortic interposition grafting in animal models, (2) determine the pertinent anatomy for this procedure, (3) validate this model in the rat and guinea pig, and (4) compare the di ...[more]

PMID: 26781075

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Project description:BackgroundToxoplasma gondii is an obligate intracellular parasite with a worldwide distribution. Congenital infection in humans and animals may lead to severe symptoms in the offspring, especially in the brain. A suitable animal model for human congenital toxoplasmosis is currently lacking. The aim of this study is to establish and validate the guinea pig as a model for human congenital toxoplasmosis by investigating the impact of the T. gondii infection dose, the duration of infection and the gestational stage at infection on the seroconversion, survival rate of dams, fate of the offspring, T. gondii DNA loads in various offspring tissues and organs and the integrity of the offspring brain.MethodsPregnant guinea pigs were infected with three different doses (10, 100, 500 oocysts) of T. gondii strain ME49 at three different time points during gestation (15, 30, 48 days post-conception). Serum of dams was tested for the presence of T. gondii antibodies using immunoblotting. T. gondii DNA levels in the dam and offspring were determined by qPCR. Offspring brains were examined histologically.ResultsWe found the survival rate of dams and fate of the offspring to be highly dependent on the T. gondii infection dose with an inoculation of 500 oocysts ending lethally for all respective offspring. Moreover, both parameters differ depending on the gestational stage at infection with infection in the first and third trimester of gestation resulting in a high offspring mortality rate. The duration of infection was found to substantially impact the seroconversion rate of dams with the probability of seroconversion exceeding 50% after day 20 post-infection. Furthermore, the infection duration of dams influenced the T. gondii DNA loads in the offspring and the integrity of offspring brain. Highest DNA levels were found in the offspring brain of dams infected for ≥ 34 days.ConclusionThis study contributes to establishing the guinea pig as a suitable model for human congenital toxoplasmosis and thus lays the foundation for using the guinea pig as a suitable animal model to study scientific questions of high topicality and clinical significance, which address the pathogenesis, diagnosis, therapy and prognosis of congenital toxoplasmosis.

Project description:Porous synthetic grafts made of poly (glycerol sebacate) (PGS) can transform into autologous vascular conduits in vivo upon degradation of PGS. A long-held doctrine in tissue engineering is the necessity to match degradation of the scaffolds to tissue regeneration. Here, we tested the impact of degradation of PGS and its derivative in an interposition model of rat common carotid artery (CCA). Previous work indicates a complete degradation of PGS within approximately 2 weeks, likely at the fast end of the spectrum. Thus, the derivation of PGS focuses on delay degradation by conjugating the free hydroxy groups in PGS with a long chain carboxylic acid: palmitic acid, one of the most common lipid components. We evaluated two of the resultant palmitate-PGS (PPGS) in this study: one containing 9% palmitate (9-PPGS) and the other16% palmitate (16-PPGS). 16-PPGS grafts had the highest patency. Ultrasound imaging showed that the lumens of 16-PPGS grafts were similar to CCA and smaller than 9-PPGS and PGS grafts 12 weeks post-operation. Immunohistological and histological examination showed an endothelialized lumens in all three types of grafts within 4 weeks. Inflammatory responses to 16-PPGS grafts were limited to the adventitial space in contrast to a more diffusive infiltration in 9-PPGS and PGS grafts in week 4. Examination of calponin+ and αSMA+ cells revealed that 16-PPGS grafts remodeled into a distinctive bi-layered wall, while the walls of 9-PPGS grafts and PGS grafts only had one thick layer of smooth muscle-like cells. Correspondingly, the expression of collagen III and elastin displayed an identical layered structure in the remodeled 16-PPGS grafts, in contrast to a more spread distribution in 9-PPGS and PGS grafts. All the three types of grafts exhibited the same collagen content and burst pressure after 12 weeks of host remodeling. However, the compliance and elastin content of 16-PPGS grafts in week 12 were closest to those of CCA. Overall, placing the degradation of PGS derived elastomer to a window of 4-12 weeks results in vascular conduits closer to arteries in a rat carotid artery interposition model over a 12-week observation period.

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Establishment of a rat and guinea pig aortic interposition graft model reveals model-specific patterns of intimal hyperplasia.

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Establishment of a rat and guinea pig aortic interposition graft model reveals model-specific patterns of intimal hyperplasia.

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