Cardiac remodeling in a new pig model of chronic heart failure: Assessment of left ventricular functional, metabolic, and structural changes using PET, CT, and echocardiography
Large animal models are needed to study disease mechanisms in heart failure (HF). In the present study we characterized the functional, metabolic, and structural changes of myocardium in a novel pig model of chronic myocardial infarction (MI) by using multimodality imaging and histology.
Methods and Results
Male farm pigs underwent a two-step occlusion of the left anterior descending coronary artery with concurrent distal ligation and implantation of a proximal ameroid constrictor (HF group), or sham operation (control group). Three months after the operation, cardiac output and wall stress were measured by echocardiography. Left ventricle (LV) volumes and mass were measured by computed tomography (CT). Myocardial perfusion was evaluated by [15O]water and oxygen consumption using [11C]acetate positron emission tomography, and the efficiency of myocardial work was calculated. Histological examinations were conducted to detect MI, hypertrophy, and fibrosis. Animals in the HF group had a large anterior MI scar. CT showed larger LV diastolic volume and lower ejection fraction in HF pigs than in controls. Perfusion and oxygen consumption in the remote non-infarcted myocardium were preserved in HF pigs as compared to controls. Global LV work and efficiency were significantly lower in HF than control pigs and was associated with increased wall stress. Histology showed myocyte hypertrophy but not increased interstitial fibrosis in the remote segments in HF pigs.
The chronic post-infarction model of HF is suitable for studies aimed to evaluate LV remodeling and changes in oxidative metabolism and can be useful for testing new therapies for HF.
KeywordsHeart failure cardiac remodeling myocardial perfusion myocardial oxygen consumption myocardial efficiency positron emission tomography
- 3.Fallavollita JA, Riegel BJ, Suzuki G, Valeti U, Canty JM. Mechanism of sudden cardiac death in pigs with viable chronically dysfunctional myocardium and ischemic cardiomyopathy. Am J Physiol 2005;289:H2688-96.Google Scholar
- 12.Kalff V, Hicks RJ, Hutchins G, Topol E, Schwaiger M. Use of carbon-11 acetate and dynamic positron emission tomography to assess regional myocardial oxygen consumption in patients with acute myocardial infarction receiving thrombolysis or coronary angioplasty. Am J Cardiol 1993;71:529-35.CrossRefPubMedGoogle Scholar
- 18.Greupner J, Zimmermann E, Grohmann A, Dübel H-P, Althoff TF, Althoff T, et al. Head-to-head comparison of left ventricular function assessment with 64-row computed tomography, biplane left cine ventriculography, and both 2- and 3-dimensional transthoracic echocardiography: Comparison with magnetic resonance imaging as the reference s. J Am Coll Cardiol 2012;59:1897-907.CrossRefPubMedGoogle Scholar
- 22.Sorensen J, Valind S, Andersson LG. Simultaneous quantification of myocardial perfusion, oxidative metabolism, cardiac efficiency and pump function at rest and during supine bicycle exercise using 1-11C-acetate PET—A pilot study. Clin Physiol Funct Imaging 2010;30:279-84.CrossRefPubMedGoogle Scholar
- 26.Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 2002;105:539-42.CrossRefPubMedGoogle Scholar