Intravenous or intramyocardial injection of apoptotic PBMC suspensions significantly reduced infarction size and improved post-AMI remodeling in a rat model.
Does intravenous or intramyocardial injection of apoptotic PBMC suspensions prevent ventricular remodelling and preserve cardiac function in a rat model of acute myocardial infarction?
In a rat model of AMI, injection of apoptotic PBMC suspensions attenuated myocardial remodelling and preserved left ventricular function by increasing elastin expression in cardiac scar tissue.
Congestive heart failure developing after acute myocardial infarction (AMI) is a major cause of morbidity and mortality. Clinical trials of cell-based therapy after AMI evidenced only a moderate benefit. We could show previously that suspensions of apoptotic peripheral blood mononuclear cells (PBMC) are able to reduce myocardial damage in a rat model of AMI. Here we experimentally examined the biochemical mechanisms involved in preventing ventricular remodelling and preserving cardiac function after AMI. Cell suspensions of apoptotic cells were injected intravenously or intramyocardially after experimental AMI induced by coronary artery ligation in rats. Administration of cell culture medium or viable PBMC served as controls. Immunohistological analysis was performed to analyse the cellular infiltrate in the ischaemic myocardium. Cardiac function was quantified by echocardiography. Planimetry of the infarcted hearts showed a significant reduction of infarction size and an improvement of post AMI remodelling in rats treated with suspensions of apoptotic PBMC (injected either intravenously or intramoycardially). Moreover, these hearts evidenced enhanced homing of macrophages and cells staining positive for c-kit, FLK-1, IGF-I and FGF-2 as compared to controls. A major finding in this study further was that the ratio of elastic and collagenous fibres within the scar tissue was altered in a favourable fashion in rats injected with apoptotic cells. Intravenous or intramyocardial injection of apoptotic cell suspensions results in attenuation of myocardial remodelling after experimental AMI, preserves left ventricular function, increases homing of regenerative cells and alters the composition of cardiac scar tissue. The higher expression of elastic fibres provides passive energy to the cardiac scar tissue and results in prevention of ventricular remodelling.
Lichtenauer et al. (Wed,) conducted a other in Acute myocardial infarction. Apoptotic peripheral blood mononuclear cell (PBMC) suspensions vs. Cell culture medium or viable PBMC was evaluated on Infarction size, post-AMI remodelling, and cardiac function. Intravenous or intramyocardial injection of apoptotic PBMC suspensions significantly reduced infarction size and improved post-AMI remodeling in a rat model.