Griffiths, Leigh G.

Currently, despite the success of percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) remains among the most commonly performed cardiac surgical procedures in the United States. Unfortunately, the use of autologous grafts in CABG presents a major clinical challenge as complications due to autologous vessel harvest and limited vessel availability pose a significant setback in the success rate of CABG surgeries. Acellular extracellular matrix (ECM) scaffolds derived from xenogeneic vascular tissues have the potential to overcome these challenges, as they offer unlimited availability and sufficient length to serve as “off-the-shelf” CABGs. Unfortunately, regardless of numerous efforts to produce a fully functional small diameter xenogeneic ECM scaffold, the combination of factors required to overcome all failure mechanisms in a single graft remains elusive. This article covers the major failure mechanisms of current xenogeneic small diameter vessel ECM scaffolds, and reviews the recent advances in the field to overcome these failure mechanisms and ultimately develop a small diameter ECM xenogeneic scaffold for CABG. Impact Statement Currently, the use of autologous vessel in coronary artery bypass graft (CABG) is common practice. However, the use of autologous tissue poses significant complications due to tissue harvest and limited availability. Developing an alternative vessel for use in CABG can potentially increase the success rate of CABG surgery by eliminating complications related to the use of autologous vessel. However, this development has been hindered by an array of failure mechanisms that currently have not been overcome. This article describes the currently identified failure mechanisms of small diameter vascular xenogeneic extracellular matrix scaffolds and reviews current research targeted to overcoming these failure mechanisms toward ensuring long-term graft patency.

PurposeThis case‐control retrospective discovery study is to identify antigenic bovine pericardium (BP) proteins that stimulate graft‐specific humoral immune response in patients implanted with glutaraldehyde fixed bovine pericardial (GFBP) heart valves.Experimental designBanked serum is collected from age‐ and sex‐matched patients who received either a GFBP or mechanical heart valve replacement. Serum IgG is isolated and used to generate poly‐polyclonal antibody affinity chromatography columns from each patient. Native and deglycosylated BP protein extracts are separately added to individual patient affinity chromatography columns, with unbound proteins washed through the column. Proteins captured in the affinity chromatography columns are submitted for proteomic identification. Differences between GFBP and mechanical heart valve replacement recipients are analyzed with Gaussian linearized modeling.ResultsCarbohydrate antigens overwhelm protein capture in the column, requiring BP protein deglycosylation prior to affinity chromatography. Nineteen BP protein antigens, which stimulated graft‐specific IgG production, are identified in patients who received GFBP valve replacements. Identified antigens are significantly over‐represented for calcium‐binding proteins.Conclusions and clinical relevancePatients implanted with GFBP valves develop a graft‐specific humoral immune response toward BP protein antigens, with 19 specific antigens identified in this work. The molecular functions of over‐represented antigens, specifically calcium‐binding proteins, may aid in understanding the underlying factors that contribute to structural valve deterioration.

Tissue autofluorescence provides fluorescence lifetime contrast between acellular tissue and that containing newly seeded cells. Fiber‐based fluorescence lifetime imaging (FLIm) can be used for tracking recellularization of engineered vascular grafts and potential matrix remodeling at large scale, without compromising sample integrity. FLIm cellular contrast was verified in a subset of samples seeded with eGFP‐labelled cells. Results suggests fiberbased FLIm is a suitable tool for monitoring recellularization of engineered tissue nondestructively.Further details can be found in the article by Alba Alfonso‐Garcia, Jeny Shklover, Benjamin E. Sherlock, et al. (e201700391). image

New techniques able to monitor the maturation of tissue engineered constructs over time are needed for a more efficient control of developmental parameters. Here, a label‐free fluorescence lifetime imaging (FLIm) approach implemented through a single fiber‐optic interface is reported for nondestructive in situ assessment of vascular biomaterials. Recellularization processes of antigen removed bovine pericardium scaffolds with endothelial cells and mesenchymal stem cells were evaluated on the serous and the fibrous sides of the scaffolds, 2 distinct extracellular matrix niches, over the course of a 7 day culture period. Results indicated that fluorescence lifetime successfully report cell presence resolved from extracellular matrix fluorescence. The recellularization process was more rapid on the serous side than on the fibrous side for both cell types, and endothelial cells expanded faster than mesenchymal stem cells on antigen‐removed bovine pericardium. Fiber‐based FLIm has the potential to become a nondestructive tool for the assessment of tissue maturation by allowing in situ imaging of intraluminal vascular biomaterials.

Significance Cardiac arrhythmias often occur in heart failure (HF) patients, but drug therapies using selective ion channel blockers have failed clinical trials and effective drug therapies remain elusive. Here we systematically study the major ionic currents during the cardiac action potential (AP) and arrhythmogenic Ca 2+ release in postinfarction HF. We found that changes in any individual current are relatively small, and alone could mislead as to consequences. However, differential changes in multiple currents integrate to shorten AP in the infarct border zone but prolong AP in the remote zone, increasing AP repolarization inhomogeneity. Our findings help explain why single channel-blocker therapy may fail, and highlight the need to understand the integrated changes of ionic currents in treating arrhythmias in HF.

Abstract Background There are limited reports of severe tricuspid valve stenosis in dogs and limited data regarding treatment and outcome. Objective To evaluate clinical signs, echocardiographic features, and outcome of balloon valvuloplasty (BV) in dogs with severe tricuspid valve stenosis (TVS) in which BV was attempted. Animals Five client-owned dogs with severe TVS. Methods Records were retrospectively reviewed and data collected regarding signalment, clinical signs, diagnostic findings, procedures, and outcome. Results All dogs were Labrador Retrievers. Presenting complaints included episodic weakness/syncope (4/5), abdominal distension (4/5), lethargy (2/5), and exercise intolerance (2/5). The median and range of measurements before BV were as follows: TV mean velocity 1.5 m/s (range 1.4–1.7 m/s); velocity-time integral (VTI) 79.8 cm (42.4–99.1 cm); and TV maximum velocity 2.9 m/s (2.3–3.2 m/s). Measurements (available for 3 of 5 dogs) after BV were as follows: TV mean velocity 1.15 m/s (0.9–1.4 m/s); VTI 44.95 cm (41.4–54.8 cm); and TV maximum velocity 1.15 m/s (1.9–2.3 m/s). The procedure was attempted in all dogs and completed in 4/5 dogs. The largest balloon diameter ranged from 15 mm to 25 mm, and length ranged from 4 cm to 5 cm. Right atrial pressure decreased in 4/5 dogs. All but 1 dog had clinical improvement after BV, but recurrence of clinical signs occurred (2/5). Tricuspid regurgitation worsened in 1 dog culminating in right heart failure and euthanasia. Conclusions and Clinical Importance BV can be an effective treatment; however, clinical signs can recur. Right heart failure due to worsened TR is a potential complication in dogs with pre-existing moderate-to-severe TR.