2012 OSU Molecular Life Sciences
Interdisciplinary Graduate Programs Symposium

 

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Poster number 35 submitted by Lucas Citro

Cardiac magnetic resonance imaging of rats treated with mesenchymal stem cells and hyperbaric hyperoxygenation following ischemia-reperfusion injury

Lucas A. Citro (Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University), Mahmood Khan (Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University), Sarath Meduru (Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University), Rajan Gogna (Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University), Esha Madan (Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University), Muthulakshmi L. Kuppusamy (Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University)

Abstract:
Adult stem cells, hyperoxia/hyperbaria, and NOS31 have all been implicated in post-MI (myocardial infarction) cardiac repair and restoration2,3. Here we examine NOS3 expression and use MRI to assess cardiac function in rats treated with hyperbaric oxygen (Ox) and mesenchymal stem cells (MSC’s) following MI. Groups: MI, Ox, MSC, and MSC+Ox. MRI was performed prior to (control) and at 1 and 4 weeks after MSC treatment (T1-weighted FLASH-cine; TR/TE = 16/1.6, FA = 10o). Other techniques were also performed.
Results: MRI. Increases (above control) at 1 and 4 weeks for all groups (exception: MI group): end-diastolic and end-systolic volumes (EDV, ESV) and ED left ventricular (LV) mass (p<0.05). With exception, no differences were observed in: stroke volume and cardiac output (p>0.05). Ejection fraction (EF) was decreased below control throughout the study (all groups) (p<0.05). MSC and MSC+Ox ED SPIO volume increased from week 1 to 4 (p<0.05).
Echocardiography. Week 1 MI EDV increased above control and week 4 MI EDV was larger than the week 1 value (p<0.05). Week 4 MI and Ox ESV values were increased (p<0.05) above week 1 MI and control values and week 4 MSC and MSC+Ox values. Week 4 MI EF and fractional shortening (FS) were decreased below control and week 1 values (p<0.05). Week 4 MSC+Ox EF and FS were larger compared to the MSC and Ox (and also, MI) groups (p<0.05).
Immunohistochemical/Western blot. For the week 4 MSC+Ox group, increases in MSC engraftment (Prussian blue), LV wall thickness, vessel and capillary density, NOS3, NOS3-mRNA (RT-PCR), connexin-43, and NOS3 phosphorylation at Ser-117, as well as decreases in fibrosis (Masson-Trichrome) and NOS3 phosphorylation at Ser-495 were observed (p<0.05).
During this study, MRI was unable to quantify cardiac restoration as accurately as echocardiography. Regardless, MSC and Ox treatments, when used as adjuvant therapies, improve LV function and decrease post-MI fibrosis through a NOS3-dependent pathway.

References:
1. Cabigas BP, Su J, Hutchins W, Shi Y, Schaefer RB, Recinos RF, et al. Hyperoxic and hyperbaric-induced cardioprotection: role of nitric oxide synthase 3. Cardiovasc Res. 2006;72(1):143-51.
2. Stamm C, Westphal B, Kleine HD, Petzsch M, Kittner C, Klinge H, et al. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet. 2003;361(9351):45-6.
3. Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet. 2004;364(9429):141-8.

Keywords: Cardiac MRI, Mesenchymal stem cells, Hyperbaric hyperoxygenation