Abstract

We hypothesized that administration of allogeneic bone marrow mesenchymal stem cells (MSCs) by intravenous, intraventricular or intramyocardial injection could improve myocardial function after survival time after cardiopulmonary resuscitation in myocardial infarcted rats. Myocardial infarction was induced by ligation of the left anterior descending artery in 54 rats (6 groups, 9 rats for each group). Left ventricular remodeling was quantitated weekly by ejection fraction (EF) measurement. One month after ligation, animals were randomized to receive injection of either MSCs 5x10(6) labeled with PKH26 in phosphate buffer solution (PBS) or PBS alone as a placebo. MSCs or PBS were administered by injection into the right femoral vein, the left ventricular cavity, or into the infracted anterior ventricular free wall. Four weeks after MSC or PBS injection, ventricular fibrillation (VF) was induced and untreated for 6 min, followed by 6 min of CPR prior to defibrillation. Hemodynamics, including cardiac index (CI), left ventricular dP/dt40 (dP/dt40), left ventricular negative dP/dt (-dP/dt) and left ventricular diastolic pressure (LVDP) were measured at baseline and hourly following return of spontaneous circulation (ROSC). Labeled MSCs were observed in 5 microm sections obtained with a cryostat from each harvested heart. Independently of the site of injection of MSCs, EF, CI, dP/dt40, -dP/dt, and LVDP were significantly improved and sustained before and after CPR in the animals treated with MSCs and were associated with significantly increased survival time when compared with the corresponding PBS treated animals.