Abstract 12394: Inducible Nitric Oxide Synthase Knockout Mice Exhibit Reduced Left Ventricular Dyssynchrony and Remodeling When Assessed Using High Frequency Ultrasound
Background: The role of increased nitric oxide (NO) from inducible NO synthase (iNOS) expression in the heart after myocardial infarction (MI) is controversial. In this study, we show that both LV dyssynchrony and remodeling are reduced in iNOS knockout (KO) mice.
Methods: Seven wild type (WT) & 6 iNOS KO mice were imaged using a 30MHz ultrasound transducer. A stack of short-axis (SA) cines and a single long-axis (LA) cine were acquired at baseline (B) at days 2, 4, 7, 14 & 28 post-MI. MI was induced with a 1-hr LAD occlusion followed by reperfusion. LV remodeling was quantified using end-systolic (ES) and end-diastolic volumes (EDV) from endocardial contours in SA cines. LV dyssynchrony was measured using dyskinesia index (DI): a displacement-based uniformity ratio estimate. Briefly, displacement data were derived from speckle tracking of LA cines, and DI was computed as the square root of the ratio of the zero-order to the sum of the zero-order and first order terms derived from Fourier transform of the radial displacement spatially distributed along the endocardial wall.
Results: Fractional shortening on D2 was similar between groups (p = NS). Both WT & KO groups exhibited similar EDV & ESV at B, D1 & D4, but both EDV & ESV were significantly reduced in KO mice from D7-D28 post-MI (p≤0.05, Fig 1A). WT mice exhibited more LV dyssynchrony than KO at every timepoint post-MI, but these differences only reached p≤0.05 on D4 & D7 (Fig 1B). A rebound in DI after D4 was observed in both groups, reflecting scar formation with a shift from dyskinetic to akinetic motion in the infarct zone.
Conclusions: Lack of iNOS expression in KO mice reduces LV dyssynchrony early and LV remodeling late after MI, indicating that global knockout of iNOS has a negative impact on the infarct healing process. Statistical differences in DI (at D4) were detected prior to any differences in EDV or ESV, suggesting that DI may be of value in predicting subsequent adverse LV remodeling.
- © 2013 by American Heart Association, Inc.