Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties

Matthew J. Price, Chung Chuan Chou, Malka Frantzen, Takashi Miyamoto, Saibal Kar, Steve Lee, Prediman K. Shah, Bradley J. Martin, Michael Lill, James S. Forrester, Peng Sheng Chen, Raj R. Makkar

Research output: Contribution to journalArticle

141 Scopus citations

Abstract

Direct intramyocardial injection of mesenchymal stem cells (MSCs) improves left ventricular ejection fraction (LVEF) and may increase ventricular arrhythmia in hearts with myocardial infarction (MI). We hypothesized that intravenous MSCs given early after acute MI would engraft in injured myocardium, improve LV function, and result in pro-arrhythmic electrical remodeling. We created an apical infarction in swine by balloon occlusion/reperfusion, administered diI-labeled allogeneic bone marrow derived MSCs intravenously 30 min post-reperfusion and measured LVEF and wall thickness at baseline, 1 month, and 3 months. Epicardial effective refractory periods (ERPs) were determined before sacrifice. At 3 months, treated pigs [n = 7] had significantly higher LVEF than controls [n = 8] (49 ± 2% vs. 44 ± 3%, P = 0.015)and significantly less wall thickening of non-infarcted myocardium. ERPs were significantly shorter than controls at all pacing cycle lengths (P ≤ 0.002), suggesting a pro-arrhythmic potential. DiI was found in the lungs, in infarct, and peri-infarct myocardium. Conclusion: IV infusion of MSCs soon after acute MI in swine improves LVEF and limits wall thickening in the remote non-infarcted myocardium, consistent with a beneficial effect on post-MI ventricular remodeling. Since there is no need for immune suppression or clinical expertise, IV infusion of MSCs may expand the potential clinical application of stem cell therapy.

Original languageEnglish (US)
Pages (from-to)231-239
Number of pages9
JournalInternational Journal of Cardiology
Volume111
Issue number2
DOIs
StatePublished - Aug 10 2006
Externally publishedYes

Keywords

  • Apical infarction
  • Occlusion
  • Reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Price, M. J., Chou, C. C., Frantzen, M., Miyamoto, T., Kar, S., Lee, S., Shah, P. K., Martin, B. J., Lill, M., Forrester, J. S., Chen, P. S., & Makkar, R. R. (2006). Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties. International Journal of Cardiology, 111(2), 231-239. https://doi.org/10.1016/j.ijcard.2005.07.036