Dataset Information

Application of polymer-mesh device to remodel left ventricular-mitral valve apparatus in ischemic mitral regurgitation.

ABSTRACT: OBJECTIVES:Ischemic mitral regurgitation (IMR) results from ischemic left ventricular (LV) distortion and remodeling, which displaces the papillary muscles and tethers the mitral valve leaflets apically. The aim of this experimental study was to examine efficacy of an adjustable novel polymer filled mesh (poly-mesh) device to reverse LV remodeling and reduce IMR. METHODS:Acute (N = 8) and chronic (8 weeks; N = 5) sheep models of IMR were studied. IMR was produced by ligation of circumflex branches to create myocardial infarction. An adjustable poly-mesh device was attached to infarcted myocardium in acute and chronic IMR models and compared with untreated sham sheep. Two- and 3-dimensional echocardiography and hemodynamic measurements were performed at baseline, post IMR, and post poly-mesh (humanely killed). RESULTS:In acute models, moderate IMR developed in all sheep and decreased to trace/mild (vena contracta: 0.50 ± 0.09 cm to 0.26 ± 0.12 cm; P < .01) after poly-mesh. In chronic models, IMR decreased in all sheep after poly-mesh, and this reduction persisted over 8 weeks (vena contracta: 0.42 ± 0.09 cm to 0.08 ± 0.12 cm; P < .01) with significant increase in the slope of end-systolic pressure-volume relationship (1.1 ± 0.5 mm Hg/mL to 2.9 ± 0.7 mm Hg/mL; P < .05). There was a significant reduction in LV volumes from chronic IMR to euthanasia stage with poly-mesh compared with sham group (%end-diastolic volume change -20 ± 11 vs 15% ± 16%, P < .01; %end-systolic volume change -14% ± 19% vs 22% ± 22%, P < .05; poly-mesh vs sham group) consistent with reverse remodeling. CONCLUSIONS:An adjustable polymer filled mesh device reduces IMR and prevents continued LV remodeling during chronic follow-up.

SUBMITTER: Kataoka A

PROVIDER: S-EPMC6237180 | biostudies-other | 2018 Apr

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Application of polymer-mesh device to remodel left ventricular-mitral valve apparatus in ischemic mitral regurgitation.

Kataoka Akihisa A Zeng Xin X Guerrero J Luis JL Kozak Adam A Braithwaite Gavin G Levine Robert A RA Vlahakes Gus J GJ Hung Judy J

The Journal of thoracic and cardiovascular surgery 20171114 4

<h4>Objectives</h4>Ischemic mitral regurgitation (IMR) results from ischemic left ventricular (LV) distortion and remodeling, which displaces the papillary muscles and tethers the mitral valve leaflets apically. The aim of this experimental study was to examine efficacy of an adjustable novel polymer filled mesh (poly-mesh) device to reverse LV remodeling and reduce IMR.<h4>Methods</h4>Acute (N = 8) and chronic (8 weeks; N = 5) sheep models of IMR were studied. IMR was produced by ligation of ci ...[more]

PMID: 29249485

Similar Datasets

Project description:Rationale: Ischemic mitral regurgitation (IMR) is frequently observed following myocardial infarction (MI) and is associated with higher mortality and poor clinical prognosis if left untreated. Accumulating evidence suggests that mitral valve (MV) leaflets actively remodel post-MI, yet the cellular mechanisms underlying these responses and how this affects tissue function remain largely unknown. Objective: We sought to elucidate MV remodeling post-MI at the tissue, cellular, and transcriptomic levels. Methods and Results: The mechanical behavior of ovine MV leaflets pre-MI and 8 weeks post-MI reveal a significant decrease in radial direction extensibility, which essentially eliminated the mechanical anisotropy typically observed in healthy MVs. Quantitative histology and ultrastructural assessment by transmission electron microscopy revealed altered leaflet composition and architecture at 8 weeks post-MI. Assessment of the MV interstitial cell (MVIC) nuclear aspect ratio, a metric of cellular deformation, revealed that MVICs were on average rounder following MI. RNA sequencing (RNA-seq) indicated that YAP-induced genes were elevated at 4 weeks post-MI and genes related to extracellular matrix organization were some of the most downregulated in sheep with IMR compared to sheep without IMR at 4 weeks post-MI. Additionally, RNA-seq revealed the possible recruitment of immune cells in this remodeling process due to the drastic elevation of CXCL9 and CLEC10A. Conclusions: This multiscale assessment revealed significant mechanical and microstructural changes due to MI. RNA-seq provided a baseline for global gene expression changes in response to MI with and without IMR and suggests YAP-induced mechanotransduction, altered expression of ECM-related genes, and recruitment of immune cells as mechanisms contributing to altered MV biomechanics post-MI. Conclusions: This multiscale assessment revealed significant mechanical and microstructural changes due to MI. RNA-seq provided a baseline for global gene expression changes in response to MI with and without IMR and suggests YAP-induced mechanotransduction, altered expression of ECM-related genes, and recruitment of immune cells as mechanisms contributing to altered MV biomechanics post-MI.

Dataset Information

Application of polymer-mesh device to remodel left ventricular-mitral valve apparatus in ischemic mitral regurgitation.

Publications

Application of polymer-mesh device to remodel left ventricular-mitral valve apparatus in ischemic mitral regurgitation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure