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Serial MRI characterization of the functional and morphological changes in mouse lung in response to cardiac remodeling following myocardial infarction
Authors:Hasan Alsaid  Weike Bao  Mary V. Rambo  Gregory A. Logan  David J. Figueroa  Stephen C. Lenhard  Charles J. Kotzer  Mark E. Burgert  Robert N. Willette  Victor A. Ferrari  Beat M. Jucker
Affiliation:1. Molecular Imaging Center of Excellence, Clinical Imaging Center, GlaxoSmithKline, King of Prussia, Pennsylvania, USA;2. Heart failure DPU, Metabolic Pathways Center of Excellence for Drug Discovery, GlaxoSmithKline, King of Prussia, Pennsylvania, USA;3. Laboratory Animal Sciences, GlaxoSmithKline, King of Prussia, Pennsylvania, USA;4. Respiratory Center of Excellence for Drug Discovery, GlaxoSmithKline, King of Prussia, Pennsylvania, USA;5. Molecular Discovery Research, GlaxoSmithKline, King of Prussia, Pennsylvania, USA;6. Discovery Statistics, GlaxoSmithKline, King of Prussia, Pennsylvania, USA;7. Division of Cardiovascular Medicine and Cardiovascular Institute, University of Pennsylvania Medical Center, Pennsylvania, USA
Abstract:The temporal evolution of heart failure and associated pulmonary congestion in rodent heart failure models has not yet been characterized simultaneously and noninvasively. In this study, MRI was used to assess the serial progression of left‐ventricular dysfunction and lung congestion in mice following myocardial infarction (MI). Cardiac and lung 1H MRI was performed at baseline and every 3 days up to 13 days postsurgery in sham and MI mice. Respiratory parameters and terminal lung mechanics were assessed followed by histological analysis. MRI revealed that the MI induced significant pulmonary congestion/edema as detected by increased MRI signal intensity and was associated with increased lung volume and reduced cardiac contractility. Pulmonary function was also depressed in MI‐mice, reflected by a reduced tidal volume and a low minute ventilation rate. Additionally, MI significantly increased lung resistance, markedly reduced lung compliance and total lung capacity and significantly increased lung weights by 57%. Significant correlations were observed between the MRI measured lung congestion, lung volume, ejection fraction, and lung wet‐weight parameters. This study demonstrates that MRI may be of significant value in evaluating therapies aimed at primary intervention for lung congestion and secondary prevention of unfavorable cardiac remodeling. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.
Keywords:magnetic resonance imaging  myocardial infarction  heart failure  pulmonary congestion
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