Improving Cardiac Function And Regulating Angiogenesis-Related Genes By Transplanting Autologous Mononuclear Bone Marrow Cells Into Myocardial Infarction Scar And Its Periphery

After myocardial infarction, some myocardium is lost and other cells in its periphery of an infarction region hibernated because of hypoperfusion. Despite substantial clinical advances in the treatment of ischemic heart disease, surgical and interventional revascularization cannot repopulate lost myocardium, and in some cases, incomplete revascularization and poor collateral development limit the perfusion of hibernating cells. This suggests that transplantation of pluripotent cells with the ability of myogenesis and angiogenesis into infracted scar and its periphery may be of benefit. Mononuclear bone marrow cells (MBMCs) contain several kinds of pluripotent adult stem cells that demonstrate a high capacity for multiplication and differentiation. In addition, several cellular bone marrow components can secrete multiple growth factors and cytokines involved in angiogenesis. However, the details of how bone marrow-derived growth factors involved in the processes after MBMCs transplantation into infracted myocardium and their interaction are still elusive. Our study try to test the therapeutic effectiveness of transplanting MBMCs into myocardial infarction scar and its periphery, and also detect the regulation of angiogenic genes involved in the processes of collateral development. Moreover, we observed the safety and feasibility of autologous MBMCs transplantation in patients with myocardial infarction during the operation of CABG.Part 1 Establishment of a Myocardial Infarction Model in Rabbit by CryoinjuryObjective Establish a myocardial infarction model in rabbits by cryoinjury. Methods twenty-one New Zealand white rabbits weighing 2.8-3.0 Kilograms were anesthetized, intubated after tracheotomy, and mechanically ventilated with room air. Under aseptic conditions, the rabbit heart was exposed through a 3-cm left lateral thoracotomy at the fifth intercostal space. Cryoinjury was produced with a metal probe (15 mm in diameter) cooled to -190°C by immersion in liquid nitrogen and applied to left ventricular free wall for 15 seconds. This procedure was repeated 15 times. The intercostal space, muscle layer and skin incision were closed. The rabbits were monitored for 4 hours postoperatively; Penicillin G was given intramuscularly. Transthoracic echocardiography was performed to measure the changes of regional cardiac function 4 weeks after cardiac cryoinjury. And then tissue samples (5mm in diameter) of infarction scar and its periphery were collected and fixed for histologic study. The samples were embedded and cut to yield sections, which were stained with hematoxylin and eosin for histologic study. Results twenty animals survived the myocardial cryoinjury procedure. The regional wall motion of myocardial infarction scar was significantly decreased accessed by M-type and two-dimensional echocardiography. The wall thickness of the infarction scar became thin obviously. Through histological study, severe fibrosis and little myocardial islands were observed in the infarction region and its periphery. Conclusion Trough cryoinjury, a myocardial infarction model in rabbits could be established successfully. Little interindividual variations make it a suitable model to study myocardial repair.