Myogenic cell transplantation improves in vivo regional performance in infarcted rabbit myocardium

Background: Although cardiac transplantation is an ideal treatment for end-stage heart disease, inadequate donor availability has stimulated efforts to manage terminally injured myocardium by other innovative methods. Autologous skeletal myoblast transplantation, or cellular cardiomyoplasty, is one method to potentially mediate myocardial repair within chronically injured hearts. However, few investigators have documented the ability of myogenic cells to alter load-insensitive indices of systolic and diastolic performance in vivo. In this study, both systolic and diastolic regional myocardial function were evaluated following left ventricular cryoinjury and compared with function after myogenic cell transplantation. Methods: Left ventricular pressure and segment length were determined in 9 rabbits by micromanometry and sonomicrometry 1 week following cryoinjury and 3 weeks after myoblast transplantation. At study termination, the extent of myoblast engraftment was determined by histologic analysis. Systolic performance was based on the linear regression of stroke work and end-diastolic segment length. Diastolic properties were evaluated by the curvilinear relationships between left ventricular pressure and strain, and left ventricular pressure and end-diastolic segment length. Results: Although mean indices of systolic performance were unchanged after cell transplantation, systolic performance improved in 3 animals. In contrast, myoblast engraftment was associated with significantly improved diastolic properties (strain and dynamic stiffness) in all animals. Conclusions: These data quantify temporal changes in regional myocardial performance and suggest that cellular cardiomyoplasty improves diastolic compliance prior to affecting systolic performance. Cellular cardiomyoplasty, a potential therapeutic-option for ischemic heart disease, appears to reverse diastolic creep and thus may represent a clinical alternative to transplantation in the near future.