Abstract 13298: First-pass MRI Reveals Distinct Mechanisms for Reduced Myocardial Perfusion Reserve Between ApoE-/- Mice on a High-cholesterol Diet and C57Bl/6 Mice on a High-fat Diet
Introduction: Reduced coronary flow reserve is an independent predictor of cardiac mortality in patients with known or suspected coronary artery disease (CAD), including nonobstructive CAD. We used first-pass perfusion MRI in mice to establish mouse models of coronary vascular disease as documented by reduced myocardial perfusion reserve (MPR).
Methods: Wild type (WT) C57Bl/6 mice (n = 6), ApoE-/- mice on a high-cholesterol diet for 18 wks (n = 5), and C57Bl/6 mice on a high-fat diet for 18 wks (HFD) (n = 7) underwent first-pass MRI at rest and at vasodilation with regadenoson (0.1 μg/g body weight). A compressed-sensing accelerated dual-contrast saturation-recovery sequence was used to acquire first-pass images. Fermi function deconvolution quantified perfusion. Cine DENSE MRI quantified myocardial strain in all mice. Histology of the aorta detected the presence or absence of atherosclerosis, and capillary density was quantified.
Results: Figure (A-C) shows example first-pass images obtained from a mouse. Quantitative perfusion results are shown in Figure D. Rest perfusion was increased in ApoE-/- vs. WT mice (Figure D, p<0.05). Stress perfusion was reduced in HFD vs. WT mice (Figure D, p<0.05). Thus, MPR was decreased in both ApoE-/- and HFD vs. WT mice (Figure E, p<0.05). Myocardial strain was reduced in ApoE-/- vs. WT mice (Figure F, p<0.05). Histology showed aortic atherosclerotic plaque in ApoE-/-, but not in HFD or WT mice. There was no difference in capillary density values between the groups of mice.
Conclusions: Using quantitative first-pass MRI, we established two mouse models of reduced MPR, one with elevated baseline perfusion and normal stress perfusion (ApoE-/- on cholesterol diet), and one with normal rest perfusion and reduced stress perfusion (WT mice on HFD). Use of these methods and models coupled with additional gene modifications promises to elucidate key molecular mechanisms that underlie coronary vascular dysfunction.
- © 2013 by American Heart Association, Inc.