Background-This experiment assessed the dose-dependent effect of a unique allogeneic STRO-3-positive mesenchymal precursor cell (MPC) on postinfarction left ventricular (LV) remodeling. The MPCs were administered in a manner that would simulate an off-the-self, early postinfarction, preventative approach to cardiac cell therapy in a sheep transmural myocardial infarct (MI) model.
Background
Studies of the biomechanical response of the left ventricle (LV) to myocardial infarction (MI) have identified infarct expansion as an important phenomenon that both initiates and sustains adverse LV remodeling. We tested the hypothesis that infarct modification via material-induced infarct stiffening and thickening limits infarct expansion and LV remodeling.
Methods
Twenty-one sheep had anteroapical infarction and were randomized to either injection of 2.6ml of saline or 2.6ml of a tissue filler material into the infarct within 3 hours of coronary occlusion. Animals were followed for 8 weeks with echocardiography to assess infarct expansion and global LV remodeling. Post-mortem morphometric measurements were performed on the excised heart to quantify infarct thickness; regional blood flow was assessed with colored microspheres. Infarct material properties were directly measured using biaxial tensile testing.
Results
Treatment animals had less infarct expansion and reduced LV dilatation 8 weeks after MI (LV systolic volumes 60.8±4.3ml vs. 80.3±6.9ml, p<0.05). Ejection fraction was greater in the treatment animals (31.0±2.6% vs. 27.6±1.3%, p<0.05). The treatment group had thicker infarcts (5.5±0.2mm vs. 2.2±0.3mm, p<0.05) and greater infarct blood flow than control groups (0.22±0.04ml/min/g vs. 0.11±0.03ml/min/g, p<0.05). The longitudinal peak strain in the treatment group was less (0.05014±0.0141) than the control group (0.1024±0.0101), indicating increased stiffness of the treated infarcts.
Conclusion
Durable infarct thickening and stiffening can be achieved by infarct biomaterial injection resulting in the amelioration of both infarct expansion and global LV remodeling. Further material optimization will allow for clinical translation of this novel treatment paradigm.
Background
The effect of mitral leaflet curvature on stress reduction is an important mechanism in optimizing valve function. We hypothesize that annuloplasty ring shape could directly influence leaflet curvature and, potentially, repair durability. We describe an echocardiographically based methodology for quantifying mitral valve geometry and its application to the characterization of ovine mitral valve geometry before and after implantation of an annuloplasty ring.
Methods
Multiple mitral annular and leaflet geometric variables were calculated for 8 naïve adult male sheep using real-time three-dimensional echocardiographic images. These indexes were recalculated after annuloplasty using a 30-mm Carpentier-Edward Physio ring (n = 4; Edwards Lifesciences, Irvine, CA) or a 30-mm saddle ring (n = 4).
Results
After implantation of the Physio ring, the annular height to commissural width ratio (AHCWR) decreased from 19.4% ± 2.3% to 11.1% ± 2.5% (p = 0.06). After implantation of the saddle ring, AHCWR increased from 19.6% ± 1.3% to 24.3% ± 1.3% (p < 0.05). Statistically significant increases in three-dimensional Gaussian curvature occurred after implantation within six defined leaflet regions (A1 to A3, P1 to P3) of the saddle ring but only within the P1 and P3 leaflet regions with the Physio ring.
Conclusions
Annuloplasty ring shape affects leaflet curvature. Implantation of a saddle ring reflecting normal human annular geometry augmented ovine annular non-planarity and increased three-dimensional leaflet curvature across the entire mitral valve surface. The Physio ring decreased annular nonplanarity and increased leaflet curvature only across limited regions of the posterior leaflet. These findings confirm the hypothesis that ring design influences leaflet curvature.
Background-Early infarct expansion after coronary occlusion compromises contractile function in perfused myocardial regions and promotes adverse long-term left ventricular (LV) remodeling. We hypothesized that injection of a tissue-expanding dermal filler material into a myocardial infarction (MI) would attenuate infarct expansion and limit LV remodeling.
Background-A comprehensive three-dimensional echocardiography based approach is applied to preoperative mitral valve (MV) analysis in patients with ischemic mitral regurgitation (IMR). This method is used to characterize the heterogeneous nature of the pathologic anatomy associated with IMR.
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