Chronic Infarction Model Research Articles

Angiomyogenesis for cardiac repair using human myoblasts as carriers of human vascular endothelial growth factor.

This study investigated the potential of human skeletal myoblast carrying human VEGF(165) for angiomyogenesis for cardiac repair. A porcine heart model of chronic infarction was created in 18 female swine by coronary artery ligation. The animals were randomized into: group 1, DMEM injected ( n=6), group 2, myoblast transplanted ( n=5) and group 3, VEGF(165) myoblast transplanted ( n=7). Three weeks later 5 ml DMEM containing 3x10(8) myoblast carrying exogenous genes were injected into 20 sites in left ventricle intramyocardially in groups 2 and 3. Group 1 animals were injected 5 ml DMEM without cells. Animals were kept on 5 mg/kg cyclosporine per day for 6 weeks. Regional blood flow was measured using fluorescent microspheres. The heart was explanted between 6-12 weeks after transplantation for histological studies. Histological examination showed survival of lac-z expressing myoblasts in host tissue. Capillary density at low power field (x100) was 57.13+/-4.20 in group 3 which was significantly higher than the other groups. Regional blood flow was significantly improved 6 and 12 weeks after transplantation, which was 2.41+/-0.11 and 3.39+/-0.11 ml(-1) min(-1) g(-1), respectively, in group 3. Left ventricular ejection fraction increased from 31.25+/-4.09% to 43.0+/-2.68% at 6 weeks in group 3. Human myoblasts are potential transgene carriers for the myocardium, in addition to strengthening the weakened myocardium through myogenesis.

191. Improvement of Myocardial Dysfunction by Therapeutic Angiogenesis Induced by Transfection of HGF Gene Using Left Ventricular Electromechanical Mapping in Porcine Chronic Myocardial Infarction Model

Top of pageAbstract Therapeutic angiogenesis using angiogenic growth factors via direct myocardial injection has been reported to improve myocardial blood flow in several animal models and patients with ischemic heart disease. In this study, we evaluated the efficacy of therapeutic angiogenesis in porcine chronic infarction model by the direct injection of hepatocyte growth factor (HGF) into myocardium using a needle injection catheter system, to evaluate the potential utility to treat IHD patients. Ischemia was induced by placing an ameroid constrictor around the proximal left circumflex artery. Four weeks later, endocardial electromechanical mapping was used to identify the area of ischemic myocardium. The area of ischemic myocardium as evidenced by uncoupling of mechanical function and electrical activity was about 10cm2 in each group. Each pig received six injections of 0.5 ml of saline or HGF (total dose 0.4 or 4mg) to ischemic area. No animal had pericardial effusion or tamponade, and no episodes of sustained ventricular arrhythmia were noted immediately after intramyocardial injection. At 1month after injection, the ischemic area (% of pre-ischemic area) was significantly reduced in HGF (0.4 or 4mg) group as compared to control (cont;100%, HGF (0.4mg); 43%lowast, HGF (4mg); 26%**,*P<0.05,**P<0.01 vs. control).Moreover, A ratio of the ischemic territory blood supply to the normal territory evaluated by microsphere beads in each animal was significantly increased in HGF (4mg) group as compared to control (cont;0.82, HGF (0.4mg); 1.02, HGF (4mg); 1.19*,*P<0.01 vs. control). These favorable outcomes provide the potential utility to treat IHD patients using catheter-based, intramyocardial injection of HGF gene Figure 1.

Design of a New Surgical Approach for Ventricular Remodeling to Relieve Ischemic Mitral Regurgitation

Mechanistic insights from 3D echocardiography (echo) can guide therapy. In particular, ischemic mitral regurgitation (MR) is difficult to repair, often persisting despite annular reduction. We hypothesized that (1) in a chronic infarct model of progressive MR, regurgitation parallels 3D changes in the geometry of mitral leaflet attachments, causing increased leaflet tethering and restricting closure; therefore, (2) MR can be reduced by restoring tethering geometry toward normal, using a new ventricular remodeling approach based on 3D echo findings. We studied 10 sheep by 3D echo just after circumflex marginal ligation and 8 weeks later. MR, at first absent, became moderate as the left ventricle (LV) dilated and the papillary muscles shifted posteriorly and mediolaterally, increasing the leaflet tethering distance from papillary muscle tips to the anterior mitral annulus (P<0.0001). To counteract these shifts, the LV was remodeled by plication of the infarct region to reduce myocardial bulging, without muscle excision or cardiopulmonary bypass. Immediately and up to 2 months after plication, MR was reduced to trace-to-mild as tethering distance was decreased (P<0.0001). LV ejection fraction, global LV end-systolic volume, and mitral annular area were relatively unchanged. By multiple regression, the only independent predictor of MR was tethering distance (r(2)=0.81). Ischemic MR in this model relates strongly to changes in 3D mitral leaflet attachment geometry. These insights from quantitative 3D echo allowed us to design an effective LV remodeling approach to reduce MR by relieving tethering.

Electromechanical characterization of chronic myocardial infarction in the canine coronary occlusion model.

Defining the presence, extent, and nature of the dysfunctional myocardial tissue remains a cornerstone in diagnostic cardiology. A nonfluoroscopic, catheter-based mapping technique that can spatially associate endocardial mechanical and electrical data was used to quantify electromechanical changes in the canine chronic infarction model. We mapped the left ventricular (LV) electromechanical regional properties in 11 dogs with chronic infarction (4 weeks after LAD ligation) and 6 controls. By sampling the location of a special catheter throughout the cardiac cycle at multiple endocardial sites and simultaneously recording local electrograms from the catheter tip, the dynamic 3-dimensional electromechanical map of the LV was reconstructed. Average endocardial local shortening (LS, measured at end systole and normalized to end diastole) and intracardiac bipolar electrogram amplitude were quantified at 13 LV regions. Endocardial LS was significantly lower at the infarcted area (1.2+/-0.9% [mean+/-SEM], P<0.01) compared with the noninfarcted regions (7.2+/-1.1% to 13. 5+/-1.5%) and with the same area in controls (15.5+/-1.2%, P<0.01). Average bipolar amplitude was also significantly lower at the infarcted zone (2.3+/-0.2 mV, P<0.01) compared with the same region in controls (10.3+/-1.3 mV) and with the noninfarcted regions (4. 0+/-0.7 to 10.2+/-1.5 mV, P<0.01) in the infarcted group. In addition, the electrical maps could accurately delineate both the location and extent of the infarct, as demonstrated by the high correlation with pathology (Pearson's correlation coefficient=0.90) and by the precise identification of the infarct border. Chronic myocardial infarcted tissue can be characterized and quantified by abnormal regional mechanical and electrical functions. The unique ability to assess the regional ventricular electromechanical properties in various myocardial disease states may become a powerful tool in both clinical and research cardiology.

Persistent high lactate level as a sensitive MR spectroscopy indicator of completed infarction

Serial proton (1H) and phosphorus-31 (31P) magnetic resonance (MR) spectroscopy of cerebral infarction was performed in rats to assess the sensitivity of these techniques for use in clinical cerebral infarction. In this experimental chronic infarction model, 31P spectroscopy tended to return to a "normal" pattern within 24 hours after induction of infarction in spite of pathologically proven completed infarction and, therefore, appeared not to be sensitive enough for clinical application. On the other hand, proton spectroscopy invariably showed persistent high lactate levels and was capable of distinguishing completed infarction from reperfused recovered brain. Persistent high lactate levels appear to be a good MR spectroscopic indicator of completed infarction.

Temporal dispersion of refractoriness: Lack of correlation with antiarrhythmic efficacy in a model of chronic infarction

Temporal dispersion of refractoriness: Lack of correlation with antiarrhythmic efficacy in a model of chronic infarction

Initiation of sustained ventricular tachyarrhythmias in a model of chronic infarction: Importance of the site of stimulation

Initiation of sustained ventricular tachyarrhythmias in a model of chronic infarction: Importance of the site of stimulation

Comparison of human ventricular activation with a canine model in chronic myocardial infarction.

Ventricular activation was studied in 20 patients with ischemic heart disease at the time of surgery for myocardial revascularization. Because most of the activation studies in man were limited to recording of epicardial potentials, a canine model of chronic infarction was also studied. Pre- and postinfarction data were recorded in dogs and correlated with the anatomy of the lesions. Epicardial Q waves, when associated with delayed epicardial activation, were diagnostic of underlying infarctions in areas of the heart that did not normally exhibit Q waves. In areas normally containing Q waves, underlying infarction was associated with Q waves greater in duration than the normal range determined for those areas of the epicardium. The experimental model of chronic infarction showed epicardial delay to be due to slowed intramyocardial activation rather than to delay in Purkinje conduction. Correlations between electrical and anatomic data in two patients suggested that, within limits, the detailed relationships between infarction and activation established with the canine model could be applied to human infarction to understand the genesis of the epicardial potentials and the ECG. The technique was also felt to have a practical clinical application in selection of areas of myocardium for vascular implants or infarctectomy.