Abstract 13298: High Frequency Speckle Tracking Echocardiography as a Sensitive Measure for Evaluating the Effects of Gene Therapy on LV Function after Myocardial Infarction in Mice
Background: Small size and rapid heart rate present challenges to obtain the spatial and temporal resolution needed to quantify subtle functional differences in mice after myocardial infarction (MI). Speckle tracking provides both qualitative and quantitative information regarding tissue deformation and motion. Here, we used it to examine the effects of cardiac-targeted gene therapy with extracellular superoxide dismutase (EcSOD), a cardioprotective antioxidant enzyme, on LV remodeling after MI. We hypothesized that speckle tracking with high frequency echo would provide a more sensitive measure of LV function than ejection fraction (EF) in mice.
Methods: MI was induced by 60 min proximal LAD occlusion in ∼10 week old C57BL/6 mice. An AAV9 vector carrying EcSOD driven by the cTnT promoter was administrated iv 10 min after reperfusion. LV geometry and function were evaluated with high frequency 2D echo (Vevo 2100) after 4 weeks.
Results: Gene delivery with systemic AAV achieved early and persistent cardiac specific gene expression as assessed by immunohistochemistry. LV end systolic volume and end diastolic volume 4 wks post-MI were 35.2% (p<0.001) and 31.2% (p<0.05) smaller in the EcSOD group (n=8) compared to controls (n=9). There was no significant difference in EF (26.9% vs. 26.7%) calculated from short-axis slices assessed base to apex. However, when longitudinal strain was derived from speckle-tracking data, the beneficial effects of EcSOD in preserving LV function became significant (-9.5±1.1 vs. -6.1±0.5, p<0.05). Moreover, regional strain analysis showed that significant functional improvements were localized to the remote zone (basal inferior and basal anterior, p<0.05), rather than the infarct or border zones (Figure).
Conclusion: Speckle tracking with high frequency echo provides the regional and temporal resolution necessary to detect subtle differences in cardiac function in mice not evident by global measures such as EF.
- © 2011 by American Heart Association, Inc.