Abstract 130: Markers of Progenitor Cell Recruitment and Differentiation Rise Early During Ischemia and Continue During Resuscitation in a Porcine Model of Acute Ischemia
Background: Clinical administration of bone marrow derived stem cells in the setting of acute myocardial infarction (AMI) improves left ventricular ejection fraction. Thymosin beta-4 (TB4) and vascular endothelial growth factor (VEGF) are linked to adult epicardial progenitor cell mobilization and neovascularization and are cardioprotective after AMI. This study investigated the time course of TB4 and VEGF during AMI, cardiac arrest, and resuscitation.
Methods: Fifteen anesthetized and instrumented domestic swine underwent balloon occlusion of the proximal LAD. During occlusion, venous blood samples were collected from the right atrium at 5 min intervals extending to 15 min after initiation of ACLS for ischemically induced VF. Plasma levels of TB4, VEGF, and MMP-9 (matrix metalloproteinase-9, selected as a marker for remodeling and repair) were measured by ELISA. Generalized linear mixed models were employed to model the time dependent change in plasma concentration. All variables were natural log transformed, except TB4 values, to normalize distributions.
Results: The average time to onset of VF after percutaneous balloon occlusion of the LAD was 28 minutes. TB4, VEGF, and MMP-9 demonstrated a statistically-significant, time-dependent increase in concentration during ischemia. Following arrest and throughout the first 15 minutes of resuscitation, MMP-9 had an unchanged rate of rise when compared to the pre-arrest, ischemic period while VEGF showed a deceleration in its time-dependent concentration trajectory and TB-4 demonstrated an acceleration. Levels of TB4 correlated with levels of VEGF (r=0.80, p<0.0001).
Conclusions: Endogenous TB4 and VEGF increase after the onset of AMI and increase through cardiac arrest and resuscitation in parallel to remodeling proteases. These markers continue to rise during successful resuscitation and may represent an endogenous mechanism to recruit undifferentiated stem cells to areas of myocardial injury.
- © 2011 by American Heart Association, Inc.