Mesenchymal stem cells improve outcomes of cardiopulmonary resuscitation in myocardial infarcted rats

Wang, Tong; Tang, Wanchun; Sun, Shijie; Wan, Zhi; Xu, Tingyan; Huang, Zitong; Weil, Max Harry

doi:10.1016/j.yjmcc.2008.11.014

« Previous Next »Journal of Molecular and Cellular Cardiology
Volume 46, Issue 3 , Pages 378-384, March 2009

Mesenchymal stem cells improve outcomes of cardiopulmonary resuscitation in myocardial infarcted rats

Tong Wang
- Weil Institute of Critical Care Medicine, 35100 Bob Hope Drive, Rancho Mirage, CA 92270, USA
- Department of Emergency Medicine, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Wanchun Tang
- Weil Institute of Critical Care Medicine, 35100 Bob Hope Drive, Rancho Mirage, CA 92270, USA
- Department of Emergency Medicine, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- The Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA
- Corresponding author. Weil Institute of Critical Care Medicine, 35100 Bob Hope Drive, Rancho Mirage, CA 92270, USA. Tel.: +1 760 778 4911; fax: +1 760 778 3468.
Shijie Sun
- Weil Institute of Critical Care Medicine, 35100 Bob Hope Drive, Rancho Mirage, CA 92270, USA
- The Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA
Zhi Wan
- Weil Institute of Critical Care Medicine, 35100 Bob Hope Drive, Rancho Mirage, CA 92270, USA
Tingyan Xu
- Weil Institute of Critical Care Medicine, 35100 Bob Hope Drive, Rancho Mirage, CA 92270, USA
Zitong Huang
- Department of Emergency Medicine, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Max Harry Weil
- Weil Institute of Critical Care Medicine, 35100 Bob Hope Drive, Rancho Mirage, CA 92270, USA
- The Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA

Received 8 August 2008; received in revised form 29 October 2008; accepted 13 November 2008. published online 08 December 2008.

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 5×10⁶ 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 μm 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.