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1.
Eur J Cardiothorac Surg ; 49(4): 1256-61; discussion 1261, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26516196

ABSTRACT

OBJECTIVES: For acute DeBakey I aortic dissection with arch tear, conventional distal reconstruction entails total arch replacement (TAR). Some surgeons at our institution have utilized an alternative reconstructive strategy-primary arch tear repair and transverse hemiarch reconstruction (THR) with concomitant antegrade thoracic endovascular aortic repair (TEVAR). We assessed early and mid-term outcomes comparing these two surgical strategies for arch tear management. METHODS: A retrospective review of a prospectively maintained institutional aortic dissection database was carried out to compare early and mid-term outcomes for patients undergoing intervention for DeBakey I aortic dissection with arch tear. Hemiarch reconstruction with concomitant antegrade TEVAR was compared against conventional TAR. Arch tear at the origin of great vessels or greater curve was primarily repaired with interrupted sutures in TEVAR patients. RESULTS: From 2006 to 2013, 61 of 284 DeBakey I aortic dissection patients undergoing intervention for arch tear were retrospectively reviewed. Thirty-one patients had TAR (TAR group) and 30 patients had hemiarch + TEVAR (TEVAR group). Demographics and clinical presentation were similar. TEVAR group had more patients presenting in cardiogenic shock [3% (n = 1) vs 13% (n = 4), P = 0.2] and tamponade [10% (n = 3) vs 23% (n = 7), P = 0.2]. Intraoperatively, TEVAR group had lower cardiopulmonary bypass (239 ± 34 vs 313 ± 80 min, p0.001) and circulatory arrest (60 ± 15 vs 78 ± 45 min, P = 0.04) times. TAR group had higher in-hospital/30-day mortality [26% (n = 8) vs 13% (n = 4), P = 0.3], but stroke rates were similar [6% (n = 2) vs 7% (n = 2), P = 1]. One-year (80 ± 7.3 vs 71 ± 8.3%), 3-year (73 ± 8.3 vs 67 ± 8.6%) and 5-year (73 ± 8.3 vs 67 ± 8.6%) actuarial survival were improved in TEVAR group, although not significantly (log-rank, P = 0.56). TEVAR promoted increased false lumen thrombosis (43 vs 85%, P = 0.002). CONCLUSION: In treating DeBakey I aortic dissection with arch tear, hemiarch replacement with primary tear repair and concomitant TEVAR is a safe alternative to conventional TAR, with improved distal aortic remodelling.


Subject(s)
Aorta, Thoracic/surgery , Aortic Aneurysm/surgery , Aortic Dissection/surgery , Blood Vessel Prosthesis Implantation/methods , Blood Vessel Prosthesis Implantation/statistics & numerical data , Blood Vessel Prosthesis/statistics & numerical data , Aged , Blood Vessel Prosthesis/adverse effects , Blood Vessel Prosthesis Implantation/mortality , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Stents
2.
Ann Thorac Surg ; 97(3): 1093-102, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24209426

ABSTRACT

We compared outcomes of posterolateral thoracotomy vs muscle-sparing thoracotomy after open thoracic operations. Twelve trials were included, comprising 571 patients in the muscle-sparing thoracotomy group and 512 patients in the posterolateral thoracotomy group. There was significantly improved shoulder internal rotation (weighted mean difference, -1.28; 95% confidence interval, -2.45 to -0.11; p = 0.03) and pain scores on day 7 (weighted mean difference, -0.76; 95% confidence interval, -1.26 to -0.27; p = 0.002) but higher seroma rates (odds ratio, 8.26; 95% confidence interval, 2.16 to 31.56; p = 0.002) in the muscle-sparing thoracotomy group compared with the posterolateral thoracotomy group. We advocate using muscle-sparing thoracotomy, especially on patients dependant on quicker recovery of shoulder function.


Subject(s)
Thoracotomy/methods , Humans , Muscle, Skeletal , Organ Sparing Treatments , Treatment Outcome
3.
J Heart Valve Dis ; 23(6): 713-20, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25790618

ABSTRACT

BACKGROUND AND AIM OF THE STUDY: Ischemic mitral regurgitation (IMR), the incidence of which is increasing, results from annular and subvalvular remodeling after myocardial infarction (MI). Although a sheep model of IMR has been used extensively over the past two decades, the ventricular, coronary and leaflet anatomy in sheep is significantly different from that in humans. In contrast, pigs are more similar to humans with regard to these parameters, and therefore may serve as a better animal to test emerging new technologies designed to treat IMR. METHODS: Twenty-nine pigs (body weight 30-35 kg) underwent left thoracotomy and ligation of the mid main circumflex and distal right posterior descending coronary arteries to create a posterolateral MI. Of these pigs, 18 were used for acute data acquisition, while 11 surviving animals in the chronic group were assessed at eight weeks after MI. Real-time three-dimensional echocardiography was performed at baseline, and at 30 min and eight weeks after MI, to assess geometric changes in the mitral annulus, mitral leaflets and left ventricle. RESULTS: Compared to baseline, the MR grade was increased significantly at eight weeks (0.7 + 0.5 versus 2.0 +/- 1.2), together with a significant decrease in left ventricular ejection fraction (40.3 +/- 6.6% versus 25.8 +/- 7.7%). Significant increases were also noted at eight weeks in the commissural width (30.1 +/- 3.2 mm versus 35.1 +/- 2.9 mm) and septolateral diameter (25.0 +/- 2.0 mm versus 33.8 +/- 5.9 mm), with a resultant increase in mitral annular area (596 +/- 85 versus 931 +/- 181 mm3) and a decrease in the annular height to commissural width ratio (15.7 +/- 2.6% versus 13.7 +/- 1.9%). The mitral valve tenting volume was also increased significantly (1577 +/- 645 versus 2440 +/- 755 mm3). The distance between the papillary muscle tips at baseline and at eight weeks was increased significantly (23.9 +/- 2.5 versus 30.9 +/- 5.2 mm), as was the distance between the posterior papillary muscle tip and the posterior commissure (20.9 +/- 2.7 versus 24.1 +/- 2.8 mm). CONCLUSION: The surgical model described here reliably replicates the changes seen in humans with IMR. Hence, this model can be used for further studies of the pathophysiology of IMR, and of any novel interventions in this challenging clinical area.


Subject(s)
Disease Models, Animal , Mitral Valve Insufficiency , Myocardial Infarction/complications , Swine , Animals , Echocardiography, Three-Dimensional/methods , Mitral Valve/pathology , Mitral Valve/physiopathology , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/etiology , Mitral Valve Insufficiency/physiopathology , Models, Anatomic , Papillary Muscles/pathology , Papillary Muscles/physiopathology , Time Factors , Ventricular Remodeling
4.
Ann Thorac Surg ; 96(2): 670-4, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23910107

ABSTRACT

PURPOSE: Transcatheter mitral valve replacement would represent a major advance in heart valve therapy. Such a device requires a specialized anchoring and sealing technology. This study was designed to test the feasibility of a novel mitral valve replacement device (the sutureless mitral valve [SMV]) designed to anchor and seal in the mitral position without need for sutures. DESCRIPTION: The SMV is a self-expanding device consisting of a custom-designed nitinol framework and a pericardial leaflet valve mechanism. EVALUATION: Ten sheep underwent successful surgical SMV device implantation. All animals underwent cardiac catheterization 6 hours postoperatively. Hemodynamic, angiographic, echocardiographic and necroscopic data were recorded. The mean aortic cross-clamp time was 9.5 ± 3.1 minutes. Echocardiography and angiography revealed excellent left ventricular systolic function, no significant perivalvular leak, no mitral valve stenosis, no left ventricular outflow tract obstruction, and no aortic valve insufficiency. Necropsy demonstrated that the SMV devices were anchored securely. CONCLUSIONS: This study demonstrates the feasibility and short-term success of sutureless mitral valve replacement using a novel SMV device.


Subject(s)
Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis Implantation/methods , Mitral Valve/surgery , Animals , Cardiac Catheterization , Equipment Design , Male , Sheep , Sutures
6.
Ann Thorac Surg ; 94(5): 1438-45, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22795059

ABSTRACT

BACKGROUND: Restoring leaflet coaptation is the primary objective in repair of ischemic mitral regurgitation (IMR). The common practice of placing an undersized annuloplasty ring partially achieves this goal by correcting annular dilation; however, annular reduction has been demonstrated to exacerbate posterior leaflet tethering. Using a sheep model of IMR, we tested the hypothesis that posterior leaflet augmentation (PLA) combined with standard annuloplasty sizing increases leaflet coaptation more effectively than undersized annuloplasty alone. METHODS: Eight weeks after posterobasal myocardial infarction, 15 sheep with 2+ or greater IMR underwent annuloplasty with either a 24-mm annuloplasty ring (24-mm group, n = 5), 30-mm ring (30-mm group, n = 5), or 30-mm ring with concomitant augmentation of the posterior leaflet (PLA group, n = 5). Using three-dimensional echocardiography, postrepair coaptation zone and posterior leaflet mobility were assessed. RESULTS: Leaflet coaptation length after repair was greater in the PLA group (4.1 ± 0.3 mm) and the 24-mm group (3.8 ± 0.5 mm) as compared with the 30-mm group (2.7 ± 0.6 mm, p < 0.01). Leaflet coaptation area was significantly greater in the PLA group (121.5 ± 6.6 mm(2)) as compared with the 30-mm group (77.5 ± 17.0 mm(2)) or the 24-mm group (92.5 ± 17.9 mm(2), p < 0.01). Posterior leaflet mobility was significantly greater in the PLA group as compared with the 30-mm group or the 24-mm group. CONCLUSIONS: Posterior leaflet augmentation combined with standard-sized annuloplasty enhances leaflet coaptation more effectively than either standard-sized annuloplasty or undersized annuloplasty alone. Increased leaflet coaptation after PLA provides redundancy to IMR repair, and may decrease incidence of both recurrent IMR and mitral stenosis.


Subject(s)
Mitral Valve Annuloplasty/methods , Mitral Valve Insufficiency/surgery , Mitral Valve/physiology , Mitral Valve/surgery , Animals , Ischemia/surgery , Sheep
7.
J Heart Valve Dis ; 21(2): 247-52, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22645862

ABSTRACT

BACKGROUND AND AIM OF THE STUDY: The treatment of pulmonary insufficiency (PI) following reconstructive surgery of the right ventricular outflow tract (RVOT) in repair of the tetralogy of Fallot remains a significant challenge. The study aim was to establish an ovine model of dilated RVOT and PI, and to quantify the degree of PI and right ventricular remodeling over an eight-week period, using magnetic resonance imaging (MRI). METHODS: Five sheep underwent baseline MRI scanning and catheterization. The weight-indexed right and left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF) and pulmonary regurgitant fraction (RF) were measured at baseline. The animals then underwent pulmonary valvectomy and transannular patch repair of the RVOT. Repeat MRI and hemodynamic measurements were obtained after an eight-week period. RESULTS: The indexed RVEDV increased from 49 +/- 4.0 ml/m2 at baseline to 80 +/- 10.3 ml/m2 at eight weeks after valvectomy (p = 0.01), while the indexed RVESV increased from 13 +/- 3.4 ml/m2 to 33 +/- 8.8 ml/m2 (p = 0.01). The indexed RVSV increased from 36 +/- 3.7 ml/m2 to 47 +/- 1.7 ml/m2 (p = 0.01). The RVEF at baseline was 74 +/- 6%, and this decreased to 59 +/- 5% at follow up (p = 0.02). The RF at baseline was 0 +/- 0% and was increased to 37 +/- 3% at eight weeks after valvectomy (p < 0.001). The left ventricular (LV) function was also diminished: LVEF at baseline was 67 +/- 2%, versus 49 +/- 10% at follow up (p = 0.01). Both, the RV and LV end-diastolic pressures were significantly elevated at follow up. CONCLUSION: All five animals developed pulmonary regurgitation sufficient to cause significant RV dilatation and diminished RV and LV functions. This model may be used to investigate novel therapeutic approaches in the treatment of this difficult clinical problem.


Subject(s)
Disease Models, Animal , Heart Ventricles/pathology , Pulmonary Artery/pathology , Pulmonary Valve Insufficiency/pathology , Sheep , Animals , Magnetic Resonance Imaging , Pulmonary Valve Insufficiency/etiology
8.
Ann Thorac Surg ; 92(3): 935-41, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21871280

ABSTRACT

BACKGROUND: Infarcted regions of myocardium exhibit functional impairment ranging in severity from hypokinesis to dyskinesis. We sought to quantify the effects of injecting a calcium hydroxyapatite-based tissue filler on the passive material response of infarcted left ventricles. METHODS: Three-dimensional finite element models of the left ventricle were developed using three-dimensional echocardiography data from sheep with a treated and untreated anteroapical infarct, to estimate the material properties (stiffness) in the infarct and remote regions. This was accomplished by matching experimentally determined left ventricular volumes, and minimizing radial strain in the treated infarct, which is indicative of akinesia. The nonlinear stress-strain relationship for the diastolic myocardium was anisotropic with respect to the local muscle fiber direction, and an elastance model for active fiber stress was incorporated. RESULTS: It was found that the passive stiffness parameter, C, in the treated infarct region is increased by nearly 345 times the healthy remote value. Additionally, the average myofiber stress in the treated left ventricle was significantly reduced in both the remote and infarct regions. CONCLUSIONS: Overall, injection of tissue filler into the infarct was found to render it akinetic and reduce stress in the left ventricle, which could limit the adverse remodeling that leads to heart failure.


Subject(s)
Biocompatible Materials/administration & dosage , Durapatite/administration & dosage , Finite Element Analysis , Heart Ventricles/physiopathology , Models, Cardiovascular , Myocardial Infarction/surgery , Prosthesis Implantation/methods , Animals , Disease Models, Animal , Echocardiography, Three-Dimensional , Heart Ventricles/diagnostic imaging , Injections, Intralesional , Myocardial Contraction/physiology , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/physiopathology , Sheep , Stress, Mechanical , Treatment Outcome
9.
Eur J Cardiothorac Surg ; 40(6): 1501-7; discussion 1507, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21546260

ABSTRACT

OBJECTIVES: Ischemic mitral regurgitation results from annular dilatation, leaflet tethering and leaflet flattening. Undersized annuloplasty corrects annular dilatation but worsens leaflet tethering and flattening. This exacerbation of abnormal leaflet geometry may contribute to poor repair results for ischemic mitral regurgitation (IMR). Using a sheep model of IMR, we hypothesized that posterior leaflet augmentation and less-extreme annular undersizing would relieve tethering and increase leaflet curvature. METHODS: Eight weeks after posterolateral infarct, 10 sheep with ≥ 2+ IMR underwent either a 24-mm planar ring annuloplasty (n = 5) or a 30-mm planar ring annuloplasty with concomitant posterior leaflet augmentation (n = 5). Real-time three-dimensional echocardiography allowed measurement of indices of leaflet curvature and tethering before and after annuloplasty. RESULTS: Comparing pre- and post-repair values in the P1, P2, and P3 leaflet regions, undersized 24-mm ring annuloplasty made no significant difference to mean septolateral curvature (0.23-0.26, 0.33-0.29, and 0.27-0.37 cm(-1), respectively), whereas leaflet augmentation in combination with a 30-mm ring annuloplasty increased septolateral curvature (P1 0.30-1.02, P2 0.31-1.23, and P3 0.35-0.84 cm(-1), p-values<0.05). The mean tethering angle formed between the annular plane and the posterior leaflet increased in all three posterior regions for the 24-mm ring group (P1 12-23°, P2 26-31°, and P3 16-25°), but decreased in all regions for the group undergoing leaflet augmentation (P1 +5 to -6°, P2 +13 to -13°, P3 +16-15°, all p-values < 0.05). CONCLUSIONS: Undersized annuloplasty exacerbates leaflet tethering. Posterior leaflet augmentation with less severe annular reduction increases leaflet curvature and decreases tethering; this technique more completely addresses the pathogenic mechanism of IMR and may improve repair durability.


Subject(s)
Mitral Valve Annuloplasty/methods , Mitral Valve Insufficiency/surgery , Mitral Valve/surgery , Animals , Disease Models, Animal , Echocardiography, Three-Dimensional/methods , Hemodynamics/physiology , Male , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/etiology , Mitral Valve Insufficiency/pathology , Myocardial Infarction/complications , Myocardial Infarction/pathology , Pericardium/transplantation , Sheep
10.
Circ Cardiovasc Interv ; 4(1): 80-7, 2011 Feb 01.
Article in English | MEDLINE | ID: mdl-21205938

ABSTRACT

BACKGROUND: Transannular patch (TAP) repair of tetralogy of Fallot often results in significant right ventricular outflow tract (RVOT) dilation and distortion. We hypothesized that insertion of Melody valves into the proximal right and left branch pulmonary arteries (PAs) would reduce pulmonary regurgitation fraction (PRF) in an ovine model of pulmonary insufficiency and dilated RVOT. METHODS AND RESULTS: Ten sheep underwent baseline cardiac catheterization, surgical pulmonary valvectomy, and TAP placement. A subset (n=5) had Melody valves (2 devices per animal) inserted into the proximal right and left PAs during the surgical procedure. Melody valves were placed distal to the right-upper-lobe (RUL) artery branch, leaving the RUL "unprotected." Preoperative MRIs (n=5) were used to determine baseline RV ejection fraction (RVEF) and left ventricular (LV) EF. All surviving animals (n=9) underwent MRI and catheterization 6 weeks postsurgery. Mean PRF was lower in the Melody valve group (15±6% versus 37±3%; P=0.014). The unprotected RUL was responsible for 64% of the PRF measured in the Melody valve group. In the non-Melody group, the RVEF was lower than baseline (P=0.003) and than in the Melody group (P=0.05). The LVEF was also lower in the non-Melody group versus baseline (P=0.004) and versus Melody (P=0.01). CONCLUSIONS: Bilateral branch PA Melody valve implantation significantly reduced PRF and altered RV and LV function favorably in a model of TAP for tetralogy of Fallot. This novel intervention may offer potential benefit in treating patients with anatomically heterogeneous disease of the RVOT.


Subject(s)
Pulmonary Valve Insufficiency/surgery , Pulmonary Valve Stenosis/surgery , Tetralogy of Fallot/surgery , Ventricular Outflow Obstruction/surgery , Animals , Cardiac Catheterization , Disease Models, Animal , Female , Heart Valve Prosthesis Implantation , Pulmonary Artery , Pulmonary Valve Insufficiency/etiology , Pulmonary Valve Stenosis/etiology , Sheep , Ventricular Outflow Obstruction/complications
11.
BMJ Case Rep ; 20112011 Aug 17.
Article in English | MEDLINE | ID: mdl-22688928

ABSTRACT

Current guidance recommends against the use of antibiotic prophylaxis around the time of dental intervention for the prevention of infective endocarditis. The authors report the case of a previously well-patient with an asymptomatic isolated ventricular septal defect (VSD) who developed evidence of infective systemic and pulmonary emboli following dental treatment. A diagnosis of severe endocarditis of a previously normal native mitral valve was made. She subsequently underwent surgical repair of her mitral valve, and closure of her VSD. She was deemed fit for discharge on parenteral antibiotics on the thirtieth postoperative day. The authors highlight the need for further re-evaluation of the issues surrounding antibiotic prophylaxis for endocarditis in the context of dental procedures.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Endocarditis, Bacterial/prevention & control , Adult , Dental Care/methods , Diagnosis, Differential , Echocardiography , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/etiology , Female , Heart Septal Defects, Ventricular/complications , Humans , Streptococcal Infections/drug therapy , Streptococcal Infections/etiology , Tomography, X-Ray Computed
12.
Ann Thorac Surg ; 91(1): 165-71, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21172507

ABSTRACT

BACKGROUND: Real-time three-dimensional (3D) echocardiography has the ability to construct quantitative models of the mitral valve (MV). Imaging and modeling algorithms rely on operator interpretation of raw images and may be subject to observer-dependent variability. We describe a comprehensive analysis technique to generate high-resolution 3D MV models and examine interoperator and intraoperator repeatability in humans. METHODS: Patients with normal MVs were imaged using intraoperative transesophageal real-time 3D echocardiography. The annulus and leaflets were manually segmented using a TomTec Echo-View workstation. The resultant annular and leaflet point cloud was used to generate fully quantitative 3D MV models using custom Matlab algorithms. Eight images were subjected to analysis by two independent observers. Two sequential images were acquired for 6 patients and analyzed by the same observer. Each pair of annular tracings was compared with respect to conventional variables and by calculating the mean absolute distance between paired renderings. To compare leaflets, MV models were aligned so as to minimize their sum of squares difference, and their mean absolute difference was measured. RESULTS: Mean absolute annular and leaflet distance was 2.4±0.8 and 0.6±0.2 mm for the interobserver and 1.5±0.6 and 0.5±0.2 mm for the intraobserver comparisons, respectively. There was less than 10% variation in annular variables between comparisons. CONCLUSIONS: These techniques generate high-resolution, quantitative 3D models of the MV and can be used consistently to image the human MV with very small interoperator and intraoperator variability. These data lay the framework for reliable and comprehensive noninvasive modeling of the normal and diseased MV.


Subject(s)
Echocardiography, Three-Dimensional , Heart Valve Diseases/diagnostic imaging , Image Processing, Computer-Assisted/methods , Mitral Valve , Models, Cardiovascular , Echocardiography, Transesophageal , Heart Valve Diseases/pathology , Humans , Monitoring, Intraoperative , Observer Variation , Predictive Value of Tests , Reproducibility of Results
13.
Ann Thorac Surg ; 90(3): 788-94, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20732497

ABSTRACT

BACKGROUND: The efficacy of annuloplasty for ischemic mitral regurgitation (IMR) has been difficult to establish. Using an established ovine model of IMR, we tested the ability of ring annuloplasty to durably relieve IMR and reverse or limit progression of left ventricular (LV) remodeling during a clinically relevant follow-up period. METHODS: A posterolateral infarction known to result in chronic IMR was initiated in 33 sheep. Echocardiography was used to assess LV end diastolic and systolic volumes and IMR (0 to 4 scale) before and 8 weeks after infarction. Eight weeks after infarction, 20 surviving animals with > or = 2+ IMR were randomized (1:1) to no treatment or undersized, semi-rigid, complete ring annuloplasty placement. LV remodeling and IMR were assessed at 4 and 6 months after infarction. RESULTS: All animals had similarly sized LV volumes at baseline (end systolic, 27.8 +/- 4.6 mL; end diastolic, 53.5 +/- 6.4 mL). The 20 randomized animals survived to complete the study. The degree of IMR before randomization was similar in treatment (2.6 +/- 0.4) and control (2.8 +/- 0.3) groups. At the 6-month follow-up, the degree of IMR was significantly less in the annuloplasty group (0.3 +/- 0.1 vs 3.4 +/- 0.6); however, LV volumes in the treatment group were not significantly different from the control group (end systolic, 82.1 +/- 15.6 vs 81.1 +/- 8.6 mL; end diastolic, 110.4 +/- 22.1 vs 111.1 +/- 16.5 mL). CONCLUSIONS: In a clinically relevant ovine model of IMR, annuloplasty provides durable relief from IMR during an extended follow-up period but does not significantly influence LV remodeling.


Subject(s)
Mitral Valve Insufficiency/surgery , Ventricular Remodeling , Animals , Disease Models, Animal , Male , Mitral Valve Insufficiency/etiology , Myocardial Infarction , Myocardial Ischemia/complications , Sheep , Time Factors
14.
Proc Natl Acad Sci U S A ; 107(25): 11507-12, 2010 Jun 22.
Article in English | MEDLINE | ID: mdl-20534527

ABSTRACT

A recent trend has emerged that involves myocardial injection of biomaterials, containing cells or acellular, following myocardial infarction (MI) to influence the remodeling response through both biological and mechanical effects. Despite the number of different materials injected in these approaches, there has been little investigation into the importance of material properties on therapeutic outcomes. This work focuses on the investigation of injectable hyaluronic acid (MeHA) hydrogels that have tunable mechanics and gelation behavior. Specifically, two MeHA formulations that exhibit similar degradation and tissue distribution upon injection but have differential moduli (approximately 8 versus approximately 43 kPa) were injected into a clinically relevant ovine MI model to evaluate the associated salutary effect of intramyocardial hydrogel injection on the remodeling response based on hydrogel mechanics. Treatment with both hydrogels significantly increased the wall thickness in the apex and basilar infarct regions compared with the control infarct. However, only the higher-modulus (MeHA High) treatment group had a statistically smaller infarct area compared with the control infarct group. Moreover, reductions in normalized end-diastolic and end-systolic volumes were observed for the MeHA High group. This group also tended to have better functional outcomes (cardiac output and ejection fraction) than the low-modulus (MeHA Low) and control infarct groups. This study provides fundamental information that can be used in the rational design of therapeutic materials for treatment of MI.


Subject(s)
Hydrogel, Polyethylene Glycol Dimethacrylate/pharmacology , Myocardial Infarction/pathology , Ventricular Remodeling/drug effects , Animals , Biocompatible Materials/chemistry , Biomechanical Phenomena , Cohort Studies , Hemodynamics , Humans , Hyaluronic Acid/chemistry , Hydrogel, Polyethylene Glycol Dimethacrylate/chemistry , Hydrogels/chemistry , Male , Polymers/chemistry , Sheep , Treatment Outcome
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