Expandable external support device to improve Saphenous Vein Graft Patency after CABG

Objectives: Low patency rates of saphenous vein grafts remain a major predicament in surgical revascularization. We examined a novel expandable external support device designed to mitigate causative factors for early and late graft failure. Methods: For this study, fourteen adult sheep underwent cardiac revascularization using two vein grafts for each; one to the LAD and the other to the obtuse marginal artery. One graft was supported with the device while the other served as a control. Target vessel was alternated between consecutive cases. The animals underwent immediate and late angiography and were then sacrificed for histopathologic evaluation. Results: Of the fourteen animals studied, three died peri-operatively (unrelated to device implanted), and ten survived the follow-up period. Among surviving animals, three grafts were thrombosed and one was occluded, all in the control group (p = 0.043). Quantitative angiographic evaluation revealed no difference between groups in immediate level of graft uniformity, with a coefficient-of-variance (CV%) of 7.39 in control versus 5.07 in the supported grafts, p = 0.082. At 12 weeks, there was a significant non-uniformity in the control grafts versus the supported grafts (CV = 22.12 versus 3.01, p < 0.002). In histopathologic evaluation, mean intimal area of the supported grafts was significantly lower than in the control grafts (11.2 mm^2 versus 23.1 mm^2 p < 0.02). Conclusions: The expandable SVG external support system was found to be efficacious in reducing SVG’s non-uniform dilatation and neointimal formation in an animal model early after CABG. This novel technology may have the potential to improve SVG patency rates after surgical myocardial revascularization

Composite transcriptome assembly of RNA-seq data in a sheep model for delayed bone healing

<p>Abstract</p> <p>Background</p> <p>The sheep is an important model organism for many types of medically relevant research, but molecular genetic experiments in the sheep have been limited by the lack of knowledge about ovine gene sequences.</p> <p>Results</p> <p>Prior to our study, mRNA sequences for only 1,556 partial or complete ovine genes were publicly available. Therefore, we developed a composite <it>de novo </it>transcriptome assembly method for next-generation sequence data to combine known ovine mRNA and EST sequences, mRNA sequences from mouse and cow, and sequences assembled <it>de novo </it>from short read RNA-Seq data into a composite reference transcriptome, and identified transcripts from over 12 thousand previously undescribed ovine genes. Gene expression analysis based on these data revealed substantially different expression profiles in standard versus delayed bone healing in an ovine tibial osteotomy model. Hundreds of transcripts were differentially expressed between standard and delayed healing and between the time points of the standard and delayed healing groups. We used the sheep sequences to design quantitative RT-PCR assays with which we validated the differential expression of 26 genes that had been identified by RNA-seq analysis. A number of clusters of characteristic expression profiles could be identified, some of which showed striking differences between the standard and delayed healing groups. Gene Ontology (GO) analysis showed that the differentially expressed genes were enriched in terms including <it>extracellular matrix</it>, <it>cartilage development</it>, <it>contractile fiber</it>, and <it>chemokine activity</it>.</p> <p>Conclusions</p> <p>Our results provide a first atlas of gene expression profiles and differentially expressed genes in standard and delayed bone healing in a large-animal model and provide a number of clues as to the shifts in gene expression that underlie delayed bone healing. In the course of our study, we identified transcripts of 13,987 ovine genes, including 12,431 genes for which no sequence information was previously available. This information will provide a basis for future molecular research involving the sheep as a model organism.</p

Evaluation of an Innovative Device for Mitral Valve Regurgitation: Experimental Acute In Vivo Results

Objective: Currently, mitral prosthetic rings are intended only to reshape the annulus. We present in vivo results of an innovative device characterized by an intraventricular segment designed to enable artificial chordae implantation and simplify leaflets and subvalvular apparatus correction. Methods: Eight sheep were employed. The first 4 underwent solely device implantation. In the last 4, primary chordae of the anterior leaflet (A2) were torn to induce severe mitral regurgitation. The severed chordae were replaced by 2 pairs of 5-0 Gore-Tex artificial chordae previously measured and anchored to the device bridge. Ease of device and chordae implantation were evaluated, and postprocedural valve competence was verified by postoperative echocardiogram. Results: The procedure was completed in all 8 sheep. In the 4 sheep with induced severe mitral regurgitation, repair could be achieved by means of artificial chordae implantation. Length of the 2 chordae implanted was 21.6 ± 2 mm and 22 ± 3 mm, respectively. The time required to suture the artificial chordae was 2.5 ± 1.2 min. Postoperative echocardiograms showed normal left ventricular ejection fraction and free motion of the mitral leaflets. Mitral regurgitation was absent in 5 cases and trivial in 3. The transvalvular peak pressure gradient was 9.5 ± 6 mm Hg, and mean gradient was 3.7 ± 4 mm Hg. Postprocedural evaluation of the heart and mitral valve showed no damage to the left ventricle wall, valve leaflets, chordae, and papillary muscles. Conclusions: In vivo tests confirm safety of the device, ease of chordal length estimation prior to implantation, short operative time, and no negative impact of the device on mitral leaflet motion, function, and structure