Abstract 18595: Matrix Metalloproteinases Activity is Reduced in Post-mi Myocardium of Diabetic Rats Assessed With Targeted Microspect-CT Imaging
Introduction: We previously demonstrated impaired angiogenesis and matrix metalloproteinases (MMP) activation in a murine model of type-1 diabetes mellitus (DM) following hindlimb ischemia using targeted radiotracers. However, the effects of DM on MMP activation post myocardial infarction (MI) remain undefined.
Methods: To evaluate the effect of DM on regional MMP activation post-MI, we performed MMP targeted microSPECT-CT imaging using a Tc-99m-labeled broad spectrum MMP inhibitor (RP805; Lantheus, USA). DM was induced in Lewis rats (n=10) after single dose streptozotocin (STZ) treatment (70mg/kg i.p.), non-treated animals served as controls (n=9). Six weeks after STZ treatment there was evidence of DM reflected by increased glucose levels (377±68mg/dL vs. 129±24 mg/dL in controls, P<0.05) and reduction of body weight (335±74g vs. 459±44g in controls, P<0.05). MI was induced by permanent LAD ligation. 1 wk (Control: n=5; DM: n=3) and 4 wks (Control: n=4; DM: n=7) post-MI rats were injected with RP805 (∼10mCi) and 60 min later Tl-201 (∼0.5mCi) followed by microSPECT-CT imaging. Hearts were excised, cut into 2mm slices, and divided into eight radial pies, for gamma well counting of activity, and corrected by tissue weight, Background, spill-up/spill-down, and decay. Regional RP805 activity was expressed as %ID/g and segmented by the relative retention of Tl-201.
Results: RP805 uptake was seen in MI region on microSPECT images of control rats at 1 wk. Quantitative analysis (fig) demonstrated a significant elevation of RP805 activity in ischemic myocardium of control rats at 1 wk post-MI (P<0.05 vs. non-ischemic), which returned to baseline levels at 4 wks post-MI. DM rats demonstrated decreased MMP activation (P<0.05 vs. control) in ischemic myocardium at 1 wk post-MI.
Conclusion: RP805 microSPECT-CT imaging could provide a novel non-invasive approach for evaluation of regional MMP activation post-MI in DM, which may predict risk for post-MI remodeling.
- © 2010 by American Heart Association, Inc.