Abstract 2431: Quantification of in-vivo Matrix Metalloproteinase Activity and Myocardial Strain Yield Unique Spatial and Temporal Patterns in a Porcine Model of Myocardial Infarction
Background: Activation of matrix metalloproteinases (MMPs) contribute to left ventricular (LV) remodeling post myocardial infarction (MI). Assessment of MMP activation has been limited to in-vitro measurements; elucidating the relationship between MMP activation and regional LV mechanics has not been possible.
Hypothesis: A Tc99m-labeled MMP targeted radiotracer (RP805, BMS) and cine MRI can define spatial and temporal patterns of MMP activation and mechanical function post-MI.
Methods: MI was created in pigs by ligation of the LCX. Cine MR and dual isotope Tl-201 and RP805 SPECT imaging was performed in control (n = 3), and infarcted pigs at 1 wk (n = 4), 2 wks (n = 5) and 4 wks (n = 3) post MI. Gamma well counting was performed on LV sections (5mm short axis slices, 16 radial segments/slice). Segments were divided based on Tl-201 activity into infarct, border and remote zones. Regional 3D LV strain was computed from MR images with a biomechanical model and correlated with regional RP805 activity.
Results: At 1 and 2 wks post MI, RP805 activity was significantly elevated in all zones vs control, with most activity localized in the MI zone (figure⇓). RP805 activity significantly declined in all zones by 4 wks and remained elevated only in the infarct zone. Radial strain was significantly lower in infarct and border vs remote zones at all time points. Extent of regional dysfunction and reduction in radial strain was persistent through 4 wks post MI.
Conclusions: Regional MMP activation was correlated with mechanical dysfunction post MI. This study demonstrated that spatial and temporal relationships between biologically active molecules, such as MMPs, and LV mechanics can be assessed in-vivo.