Gavin Braithwaite

Polymer Injection Therapy to Reverse Remodel the Papillary Muscles Efficacy in Reducing Mitral Regurgitation in a Chronic Ischemic Model

Background— Ischemic mitral regurgitation (MR) results from displacement of the papillary muscles caused by ischemic ventricular distortion. Progressive left ventricular (LV) remodeling has challenged therapy. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) hydrogel polymer into the myocardium in chronic MR despite advanced LV remodeling. Methods and Results— Ten sheep underwent ligation of the circumflex branches to produce chronic ischemic MR over 8 weeks. PVA was injected into the myocardium underlying the infarcted papillary muscle. Two-dimensional and 3D echocardiograms and hemodynamic data were obtained before infarct (baseline), before PVA (chronic MR), and after PVA. PVA injection significantly decreased MR from moderate to severe to trace (MR vena contracta, 5.8±1.2 to1.8±1.3 mm; chronic MR to post-PVA stage; P =0.0003). This was associated with a decrease in infarcted papillary muscle–to–mitral annulus tethering distance (30.3±5.7 to 25.9±4.6 mm, P =0.02), tenting volume (1.8±0.7 to 1.4±0.5 mL, P =0.01), and leaflet closure area (8.8±1.3 cm2to 7.6±1.3 cm2, P =0.004) from chronic MR to post-PVA stages. PVA was not associated with significant decreases in LV ejection fraction (41±3% versus 40±3%, P =NS), end-systolic elastance, τ (82±36 ms to 72±26, P =NS), or LV stiffness coefficient (0.05±0.04 to 0.03±0.01). Conclusions— PVA hydrogel injections improve coaptation and reduce remodeling in chronic MR without impairing LV systolic and diastolic function. This new approach offers a potential alternative for relieving tethering and ischemic MR by correcting papillary muscle position.Background—Ischemic mitral regurgitation (MR) results from displacement of the papillary muscles caused by ischemic ventricular distortion. Progressive left ventricular (LV) remodeling has challenged therapy. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) hydrogel polymer into the myocardium in chronic MR despite advanced LV remodeling. Methods and Results—Ten sheep underwent ligation of the circumflex branches to produce chronic ischemic MR over 8 weeks. PVA was injected into the myocardium underlying the infarcted papillary muscle. Two-dimensional and 3D echocardiograms and hemodynamic data were obtained before infarct (baseline), before PVA (chronic MR), and after PVA. PVA injection significantly decreased MR from moderate to severe to trace (MR vena contracta, 5.8±1.2 to1.8±1.3 mm; chronic MR to post-PVA stage; P=0.0003). This was associated with a decrease in infarcted papillary muscle–to–mitral annulus tethering distance (30.3±5.7 to 25.9±4.6 mm, P=0.02), tenting volume (1.8±0.7 to 1.4±0.5 mL, P=0.01), and leaflet closure area (8.8±1.3 cm2to 7.6±1.3 cm2, P=0.004) from chronic MR to post-PVA stages. PVA was not associated with significant decreases in LV ejection fraction (41±3% versus 40±3%, P=NS), end-systolic elastance, &tgr; (82±36 ms to 72±26, P=NS), or LV stiffness coefficient (0.05±0.04 to 0.03±0.01). Conclusions—PVA hydrogel injections improve coaptation and reduce remodeling in chronic MR without impairing LV systolic and diastolic function. This new approach offers a potential alternative for relieving tethering and ischemic MR by correcting papillary muscle position.

Polymer Injection Therapy to Reverse Remodel the Papillary MusclesClinical Perspective

Background— Ischemic mitral regurgitation (MR) results from displacement of the papillary muscles caused by ischemic ventricular distortion. Progressive left ventricular (LV) remodeling has challenged therapy. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) hydrogel polymer into the myocardium in chronic MR despite advanced LV remodeling. Methods and Results— Ten sheep underwent ligation of the circumflex branches to produce chronic ischemic MR over 8 weeks. PVA was injected into the myocardium underlying the infarcted papillary muscle. Two-dimensional and 3D echocardiograms and hemodynamic data were obtained before infarct (baseline), before PVA (chronic MR), and after PVA. PVA injection significantly decreased MR from moderate to severe to trace (MR vena contracta, 5.8±1.2 to1.8±1.3 mm; chronic MR to post-PVA stage; P =0.0003). This was associated with a decrease in infarcted papillary muscle–to–mitral annulus tethering distance (30.3±5.7 to 25.9±4.6 mm, P =0.02), tenting volume (1.8±0.7 to 1.4±0.5 mL, P =0.01), and leaflet closure area (8.8±1.3 cm2to 7.6±1.3 cm2, P =0.004) from chronic MR to post-PVA stages. PVA was not associated with significant decreases in LV ejection fraction (41±3% versus 40±3%, P =NS), end-systolic elastance, τ (82±36 ms to 72±26, P =NS), or LV stiffness coefficient (0.05±0.04 to 0.03±0.01). Conclusions— PVA hydrogel injections improve coaptation and reduce remodeling in chronic MR without impairing LV systolic and diastolic function. This new approach offers a potential alternative for relieving tethering and ischemic MR by correcting papillary muscle position.Background—Ischemic mitral regurgitation (MR) results from displacement of the papillary muscles caused by ischemic ventricular distortion. Progressive left ventricular (LV) remodeling has challenged therapy. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) hydrogel polymer into the myocardium in chronic MR despite advanced LV remodeling. Methods and Results—Ten sheep underwent ligation of the circumflex branches to produce chronic ischemic MR over 8 weeks. PVA was injected into the myocardium underlying the infarcted papillary muscle. Two-dimensional and 3D echocardiograms and hemodynamic data were obtained before infarct (baseline), before PVA (chronic MR), and after PVA. PVA injection significantly decreased MR from moderate to severe to trace (MR vena contracta, 5.8±1.2 to1.8±1.3 mm; chronic MR to post-PVA stage; P=0.0003). This was associated with a decrease in infarcted papillary muscle–to–mitral annulus tethering distance (30.3±5.7 to 25.9±4.6 mm, P=0.02), tenting volume (1.8±0.7 to 1.4±0.5 mL, P=0.01), and leaflet closure area (8.8±1.3 cm2to 7.6±1.3 cm2, P=0.004) from chronic MR to post-PVA stages. PVA was not associated with significant decreases in LV ejection fraction (41±3% versus 40±3%, P=NS), end-systolic elastance, &tgr; (82±36 ms to 72±26, P=NS), or LV stiffness coefficient (0.05±0.04 to 0.03±0.01). Conclusions—PVA hydrogel injections improve coaptation and reduce remodeling in chronic MR without impairing LV systolic and diastolic function. This new approach offers a potential alternative for relieving tethering and ischemic MR by correcting papillary muscle position.

Efficacy of polymer injection for ischemic mitral regurgitation: persistent reduction of mitral regurgitation and attenuation of left ventricular remodeling.

OBJECTIVES The aim of this study was to examine the chronic effects of polyvinyl-alcohol (PVA) injection on mitral regurgitation (MR) reduction, mitral valve geometry, and left ventricular (LV) remodeling in a chronic ischemic MR sheep model. BACKGROUND Previous studies have demonstrated acute efficacy of PVA hydrogel polymer injection into infarcted myocardium underlying the papillary muscle to relieve MR by papillary muscle repositioning. However, the chronic efficacy of PVA injection in the chronic infarction setting remains unclear. METHODS Sixteen sheep developed chronic MR 8 weeks after induced inferoposterior myocardial infarction. Ten consecutive sheep underwent PVA injection (PVA group) and 6 sheep served as control subjects with saline injection. Epicardial 2-/3-dimensional echocardiography was performed at the baseline, chronic MR (pre-injection), and sacrifice (8 weeks after injection) stages. RESULTS Both groups were comparable at the baseline and chronic MR stages. At sacrifice, MR decreased from moderate to trace or mild (vena contracta: 0.17 ± 0.08 cm vs. 0.56 ± 0.10 cm, p < 0.001) in the PVA group but progressed to moderate to severe in the control group. End-systolic and -diastolic volumes remained stable in the PVA group but increased significantly in the control group (both p < 0.05). At sacrifice, compared with the control group, the PVA group had significantly less left ventricular remodeling (end-systolic volume: 41.1 ± 10.4 ml vs. 55.9 ± 12.4 ml, p < 0.05), lower MR severity (vena contracta: 0.17 ± 0.08 cm vs. 0.60 ± 0.14 cm, p < 0.01), and favorable changes in mitral valve geometry. CONCLUSIONS Polymer injection in a chronic ischemic MR model results in persistent reduction of MR and attenuation of continued left ventricular remodeling over 8 weeks of follow-up.

Quantifying the lubricity of mechanically tough polyvinyl alcohol hydrogels for cartilage repair

Polyvinyl alcohol hydrogels are biocompatible and can be used as synthetic articular cartilage. Their mechanical characteristics can be tailored by various techniques such as annealing or blending with other hydrophilic polymers. In this study, we quantified the coefficient of friction of various candidate polyvinyl alcohol hydrogels against cobalt–chrome alloy or swine cartilage using a new rheometer-based method. We investigated the coefficient of friction of polyvinyl alcohol–only hydrogels and blends with polyethylene glycol, polyacrylic acid, and polyacrylamide against swine cartilage and polished cobalt–chrome surfaces. The addition of the functional groups to polyvinyl alcohol, such as acrylamide (semi-interpenetrating network) and acrylic acid (blend), significantly reduced the coefficient of friction. The coefficient of friction of the polyvinyl alcohol–only hydrogel was measured as 0.4 ± 0.03 against cobalt–chrome alloy, and 0.09 ± 0.004 against cartilage, while those measurements for the polyvinyl alcohol–polyacrylic acid blends and polyvinyl alcohol–polyacrylamide semi-interpenetrating network were 0.07 ± 0.01 and 0.1 ± 0.003 against cobalt–chrome alloy, and 0.03 ± 0.001 and 0.02 ± 0.001 against cartilage, respectively. There was no significant or minimal difference in the coefficient of friction between samples from different regions of the knee, or animals, or when the cartilage samples were frozen for 1 day or 2 days before testing. However, changing lubricant from deionized water to ionic media, for example, saline or simulated body fluid, increased the coefficient of friction significantly.

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

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.

29 – Characterization of Physical, Chemical, and Mechanical Properties of UHMWPE

There are many properties to consider when developing a new ultra-high molecular weight polyethylene (UHMWPE) material for implant applications. The characteristics of the UHMWPE powder may be measured to verify that there are not variations in different manufacturing lots. After consolidation, where the polyethylene powder is compressed into a solid slab of material via ram extrusion, compression molding, or other techniques including isostatic pressing, manufacturers will test the solid polyethylene slab to determine the quality of the consolidation, and to determine if any deleterious effects have occurred. Highly cross-linked UHMWPE is commonly used now, whereby the polyethylene slab is exposed to radiation, which forms chemical bonds between polymer chains. Several analytical techniques have been developed to assess if the material has been exposed to enough radiation to improve the desirable properties of the UHMWPE, while ensuring that other properties are not diminished by the radiation.

Oxidative-induction time as a measure of vitamin E concentration in ultra-high molecular weight polyethylene

A novel, sensitive method for quantifying an equivalent antioxidant concentration, specifically vitamin E (VE), in postprocessed ultra-high molecular weight polyethylene (UHMWPE) for orthopedic implants is presented. This method correlates oxidative-induction time (OIT) determined from differential scanning calorimetry with starting VE weight percent in solvent blended samples using a nonlinear power law fit. The generated calibration curve reliably determined the equivalent VE concentration down to blended concentrations lower than 0.007 wt %, with a measurement uncertainty of 0.0009 wt %. This measurement uncertainty implies a detection limit that is significantly lower than currently achievable with the established method using Fourier transform infrared spectroscopy to calculate a VE index. However, exact processes that are influencing the OIT in irradiated materials are unclear at this time. UHMWPE blended with VE in powder, consolidated and irradiated form were investigated. In addition, intralaboratory results give support that this technique may lend itself to standardization in quality control and verification.

DEVELOPMENT AND APPLICATION OF POLYMER-MATRIX DEVICE TO REMODEL LEFT VENTRICULAR – MITRAL VALVE APPARATUS IN ISCHEMIC MITRAL REGURGITATION

Ischemic mitral regurgitation (IMR) results from mitral valve (MV) tethering by ischemic left ventricular (LV) distortion. Ring annuloplasty therapy has limitations as it does not directly address LV remodeling and is associated with recurrent IMR due to continued remodeling. We aimed to explore a

Polymer Injection Therapy to Reverse Remodel the Papillary MusclesClinical Perspective: Efficacy in Reducing Mitral Regurgitation in a Chronic Ischemic Model

Background— Ischemic mitral regurgitation (MR) results from displacement of the papillary muscles caused by ischemic ventricular distortion. Progressive left ventricular (LV) remodeling has challenged therapy. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) hydrogel polymer into the myocardium in chronic MR despite advanced LV remodeling. Methods and Results— Ten sheep underwent ligation of the circumflex branches to produce chronic ischemic MR over 8 weeks. PVA was injected into the myocardium underlying the infarcted papillary muscle. Two-dimensional and 3D echocardiograms and hemodynamic data were obtained before infarct (baseline), before PVA (chronic MR), and after PVA. PVA injection significantly decreased MR from moderate to severe to trace (MR vena contracta, 5.8±1.2 to1.8±1.3 mm; chronic MR to post-PVA stage; P =0.0003). This was associated with a decrease in infarcted papillary muscle–to–mitral annulus tethering distance (30.3±5.7 to 25.9±4.6 mm, P =0.02), tenting volume (1.8±0.7 to 1.4±0.5 mL, P =0.01), and leaflet closure area (8.8±1.3 cm2to 7.6±1.3 cm2, P =0.004) from chronic MR to post-PVA stages. PVA was not associated with significant decreases in LV ejection fraction (41±3% versus 40±3%, P =NS), end-systolic elastance, τ (82±36 ms to 72±26, P =NS), or LV stiffness coefficient (0.05±0.04 to 0.03±0.01). Conclusions— PVA hydrogel injections improve coaptation and reduce remodeling in chronic MR without impairing LV systolic and diastolic function. This new approach offers a potential alternative for relieving tethering and ischemic MR by correcting papillary muscle position.Background—Ischemic mitral regurgitation (MR) results from displacement of the papillary muscles caused by ischemic ventricular distortion. Progressive left ventricular (LV) remodeling has challenged therapy. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) hydrogel polymer into the myocardium in chronic MR despite advanced LV remodeling. Methods and Results—Ten sheep underwent ligation of the circumflex branches to produce chronic ischemic MR over 8 weeks. PVA was injected into the myocardium underlying the infarcted papillary muscle. Two-dimensional and 3D echocardiograms and hemodynamic data were obtained before infarct (baseline), before PVA (chronic MR), and after PVA. PVA injection significantly decreased MR from moderate to severe to trace (MR vena contracta, 5.8±1.2 to1.8±1.3 mm; chronic MR to post-PVA stage; P=0.0003). This was associated with a decrease in infarcted papillary muscle–to–mitral annulus tethering distance (30.3±5.7 to 25.9±4.6 mm, P=0.02), tenting volume (1.8±0.7 to 1.4±0.5 mL, P=0.01), and leaflet closure area (8.8±1.3 cm2to 7.6±1.3 cm2, P=0.004) from chronic MR to post-PVA stages. PVA was not associated with significant decreases in LV ejection fraction (41±3% versus 40±3%, P=NS), end-systolic elastance, &tgr; (82±36 ms to 72±26, P=NS), or LV stiffness coefficient (0.05±0.04 to 0.03±0.01). Conclusions—PVA hydrogel injections improve coaptation and reduce remodeling in chronic MR without impairing LV systolic and diastolic function. This new approach offers a potential alternative for relieving tethering and ischemic MR by correcting papillary muscle position.

Polymer Injection Therapy to Reverse Remodel the Papillary Muscles

Background— Ischemic mitral regurgitation (MR) results from displacement of the papillary muscles caused by ischemic ventricular distortion. Progressive left ventricular (LV) remodeling has challenged therapy. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) hydrogel polymer into the myocardium in chronic MR despite advanced LV remodeling. Methods and Results— Ten sheep underwent ligation of the circumflex branches to produce chronic ischemic MR over 8 weeks. PVA was injected into the myocardium underlying the infarcted papillary muscle. Two-dimensional and 3D echocardiograms and hemodynamic data were obtained before infarct (baseline), before PVA (chronic MR), and after PVA. PVA injection significantly decreased MR from moderate to severe to trace (MR vena contracta, 5.8±1.2 to1.8±1.3 mm; chronic MR to post-PVA stage; P =0.0003). This was associated with a decrease in infarcted papillary muscle–to–mitral annulus tethering distance (30.3±5.7 to 25.9±4.6 mm, P =0.02), tenting volume (1.8±0.7 to 1.4±0.5 mL, P =0.01), and leaflet closure area (8.8±1.3 cm2to 7.6±1.3 cm2, P =0.004) from chronic MR to post-PVA stages. PVA was not associated with significant decreases in LV ejection fraction (41±3% versus 40±3%, P =NS), end-systolic elastance, τ (82±36 ms to 72±26, P =NS), or LV stiffness coefficient (0.05±0.04 to 0.03±0.01). Conclusions— PVA hydrogel injections improve coaptation and reduce remodeling in chronic MR without impairing LV systolic and diastolic function. This new approach offers a potential alternative for relieving tethering and ischemic MR by correcting papillary muscle position.Background—Ischemic mitral regurgitation (MR) results from displacement of the papillary muscles caused by ischemic ventricular distortion. Progressive left ventricular (LV) remodeling has challenged therapy. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) hydrogel polymer into the myocardium in chronic MR despite advanced LV remodeling. Methods and Results—Ten sheep underwent ligation of the circumflex branches to produce chronic ischemic MR over 8 weeks. PVA was injected into the myocardium underlying the infarcted papillary muscle. Two-dimensional and 3D echocardiograms and hemodynamic data were obtained before infarct (baseline), before PVA (chronic MR), and after PVA. PVA injection significantly decreased MR from moderate to severe to trace (MR vena contracta, 5.8±1.2 to1.8±1.3 mm; chronic MR to post-PVA stage; P=0.0003). This was associated with a decrease in infarcted papillary muscle–to–mitral annulus tethering distance (30.3±5.7 to 25.9±4.6 mm, P=0.02), tenting volume (1.8±0.7 to 1.4±0.5 mL, P=0.01), and leaflet closure area (8.8±1.3 cm2to 7.6±1.3 cm2, P=0.004) from chronic MR to post-PVA stages. PVA was not associated with significant decreases in LV ejection fraction (41±3% versus 40±3%, P=NS), end-systolic elastance, &tgr; (82±36 ms to 72±26, P=NS), or LV stiffness coefficient (0.05±0.04 to 0.03±0.01). Conclusions—PVA hydrogel injections improve coaptation and reduce remodeling in chronic MR without impairing LV systolic and diastolic function. This new approach offers a potential alternative for relieving tethering and ischemic MR by correcting papillary muscle position.