Improved outcomes of cardiopulmonary resuscitation in rats with myocardial infarction treated with allogenic bone marrow mesenchymal stem cells

OBJECTIVE: We hypothesized that rats in which myocardial infarction had been treated with mesenchymal stem cells (MSCs) would have better outcomes following the global myocardial ischemia of cardiac arrest and cardiopulmonary resuscitation (CPR) compared with rats in which myocardial infarction had been treated with phosphate buffer solution (PBS). DESIGN: Prospective, randomized controlled study. SETTING: University-affiliated research institute. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Myocardial infarction was induced in 18 male Sprague-Dawley rats. Four weeks later, animals were randomized to receive 5 x 10 MSCs labeled with red fluorescent dye gel (PKH26) in PBS or a PBS-alone injection into right femoral vein. MEASUREMENTS AND MAIN RESULTS: Echocardiographically measured myocardial function, including ejection fraction, left ventricular end-diastolic volume, and left ventricular end-systolic volume, was quantitated 2 and 4 weeks after administering MSCs or PBS. Four weeks after MSCs or PBS injection, 6 minutes of ventricular fibrillation (VF) and 6 minutes of CPR were performed before defibrillation. Myocardial function, including cardiac index, left ventricular, dP/dt max (dP/dt max), left ventricular negative dP/dt min (-dP/dt min), and left ventricular diastolic pressure, was measured before inducing VF and hourly following return of spontaneous circulation. Labeled MSCs were observed in 5-mum cryostat sections from each harvested heart. Significant improvements in ejection fraction, left ventricular end-diastolic volume, left ventricular end-systolic volume, cardiac index, dP/dt max, -dP/dt min, and left ventricular diastolic pressure followed injection of MSCs before inducing VF. Following return of spontaneous circulation, myocardial function was significantly better in animals pretreated with MSCs; this was associated with significantly increased duration of postresuscitation survival. CONCLUSIONS: Myocardial function before and after CPR and duration of survival after CPR were significantly improved in animals in which myocardial infarction was treated with MSCs. MSCs existing in the myocardium resisted a secondary ischemic event and provided better postresuscitation myocardial function.