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Impact Of Autologous Skeletal Myoblast Engraftment On Ventricular Function In A Canine Model Of Chronic Heart Failure

Posted on:2004-04-29Degree:MasterType:Thesis
Country:ChinaCandidate:Q LiFull Text:PDF
GTID:2144360092499720Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objectives: In Western countries such as the United States and Europe, ischemic heart disease and myocardial ischemia-induced heart failure are major health concerns because of their high morbilities and high mortalities. In China, along with improved medical care and advanced therapeutic treatments, ageing of the population and increased post-infarction survival rates, the incidence of heart failure is also expected to be increased in the forthcoming years. Myocardial ischemia results in the necrosis and the apoptosis of cardiac myocyte. Because cardiac myocyte is, generally believing, terminally differentiated cell and lacks capability to be regenerated after ischemic insults or myocardiac infarction. Instead, the injured or infarcted myocardium will be replaced by fibrosis and becomes a non-contracting fibrous scar. As the disease progresses, heart failure will be developed. Heart failure has been generally believed not only a disease of heart but also a manifestation of systemic neuro-hormonal imbalance. As the initial insults, myocardial ischemia plays a critical role of heart failure. Among pathogenesis phenomena of heart failure, leftventricular remodeling (the changes in left ventricular geographic structure and shape due to injured myocytes, infracted myocardium, fiborosis, scar and hypertrophied survived myocytes) become the most critical feature of the disease and it further facilitates the deterioration of heart failure. Thus, the key approaches of treatments for heart failure is how to rescue myocytes from ischemic insults or promote the regeneration of cardiac myocytes, and to prevent, even reverse left ventriclar remodeling. Although advances of surgical techniques, medical managements, and cardiac interventional therapy can relieve the symptoms of myocardial ischemia and heart failure, they can't regenerate cardiac myocytes or prevent the further myocardial deterioration. Therefore, "cellular therapy" creates a novel therapy to the ischemic heart disease, the objective of which is to engraft cells with capability of regeneration and differentiation into infarcted myocardium in order to replace the necrotic cardiac myocytes and restore cardiac function. Among multiple cell types for the engraftment, skeletal myoblasts, which have the potential of regeneration and of repairing injured skeletal muscle, have attracted lots of medical investigators' interests, because they have many advantages compared with other cells, such as the contractility, higher efficiency of cell culture, the autologous cells source, needless of immunosuppression, and so on. Consequently, the purpose of this study is to test whetherautologous skeletal myoblasts engraftment can restore cardiac contractile strength in canine model of chronic heart failure due to repeated coronary microembolizations.Methods: All 22 mongrel dogs (Age> 1 year old, Weight: 25~30kg) were performed the first open-chest surgery to implant instruments for the cardiac function measurements during the chronic studies. After dogs recovering from the instrumentation surgery and finishing the conscious study training, the first conscious experiment was performed to record the baseline normal assessments. (Described below) Following this, chronic heart failure (CHF) was induces by repeated coronary microembolization over the course of 4~8 weeks in all dogs. 25000~50000 microspheres (90~120um) were injected each day into the left anterior descending branch of coronary artery through the previously implanted cannula. Until left ventricular end-diastolic pressure (LVEDP) increased to ≥20mmHg, the peak positive derivative of left ventricular pressure (LVdp/dt) decreased to ≤2200mmHg and both hemodynamic parameters kept stable, the effective and stable CHF was confirmed. So the second conscious experiment was performed to record the data of CHF. Then, myoblasts group 1 (n=5) were performed the second open-chest surgery to inject skeletal myoblasts into the infracted myocardium with a 25-gauge needle under direct vision. Skeletal myobl...
Keywords/Search Tags:heart failure, autologous skeletal myoblasts, engraftment, cellular therapy, myocardial ischemia
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