title: Effect of chronic left ventricular unloading on myocardial remodeling: Multimodal assessment of two heterotopic heart transplantation techniques.
abstract: BACKGROUND
  Cardiac recovery is possible by means of mechanical unloading yet remains rare. Excessive unloading-associated myocardial atrophy and fibrosis may adversely affect the process of reverse remodeling. In this study, we sought to evaluate the effect of different intensities of chronic left ventricular (LV) unloading on myocardial remodeling.
  
  
  METHODS
  Twenty-five isogenic Lewis rats underwent complete LV unloading (CU, n = 15) induced by heterotopic heart transplantation or partial LV unloading (PU, n = 10) by heterotopic heart-lung transplantation. Information obtained from serial echocardiography, 2-deoxy-2[(18)F]fluoro-d-glucose ((18)F-FDG)-positron emission tomography, and an LV pressure-volume catheter were used to evaluate the morphology, glucose metabolism, and hemodynamic performance of the orthotopic hearts and heterotopic transplants over 4 weeks. Cell size, collagen content, tissue cytokines (interleukin [IL]-1α, IL-2, IL-6, IL-10, tumor necrosis factor-α, and vascular endothelial growth factor), and matrix metalloproteinase-2 and -9 were also determined. The recorded parameters included LV end-systolic dimension, LV end-diastolic dimension, posterior wall thickness, diastolic interventricular septum thickness, LV fractional shortening, and LV ejection fraction.
  
  
  RESULTS
  We demonstrated an LV load-dependent relationship using echo-based structural (left posterior wall thickness, diastolic interventricular septum thickness, and left ventricular end-diastolic dimension) and functional (LV fractional shortening and LV ejection fraction) parameters, as well as an (18)F-FDG uptake (all p < 0.05). This load-dependent relationship was also evidenced in measurements from the pressure-volume conductance catheter (stroke volume, stroke work, cardiac output, dP/dTmax, and -dP/dTmin; all p < 0.05). Significant myocardial atrophy and fibrosis were observed in unloaded hearts, whereas concentrations of cytokines and matrix metalloproteinases were comparable in both unloading conditions.
  
  
  CONCLUSIONS
  Partial and complete unloading affected the remodeling of non-failing hearts in a rodent model to different extents on myocardial atrophy, fibrosis, glucose metabolism, and mechanical work. Cardiac atrophy is the prominent change after mechanical unloading, which exaggerates the proportion of total collagen that is responsible for diastolic dysfunction.
authors.affiliation: Department of Cardiovascular Surgery And Heart Transplantation, Centre Hospitalier Universitaire-Nancy, Nancy, France; School of Surgery, Unité Institut National de la Santé et de la Recherche Médicale 1116, Université de Lorraine, Nancy, France; Department of Cardiothoracic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Surgery And Heart Transplantation, Centre Hospitalier Universitaire-Nancy, Nancy, France; School of Surgery, Unité Institut National de la Santé et de la Recherche Médicale 1116, Université de Lorraine, Nancy, France. Electronic address: pablomaureira@hotmail.com.
authors.forename: Pablo
authors.initials: P
authors.lastname: Maureira
authors.affiliation: Departments of (d)Pathology.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Gauchotte
authors.affiliation: School of Surgery, Unité Institut National de la Santé et de la Recherche Médicale 1116, Université de Lorraine, Nancy, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Falanga
authors.affiliation: School of Surgery, Unité Institut National de la Santé et de la Recherche Médicale 1116, Université de Lorraine, Nancy, France.
authors.forename: Venessa
authors.initials: V
authors.lastname: Marie
authors.affiliation: Cardiology.
authors.forename: Arnauld
authors.initials: A
authors.lastname: Olivier
authors.affiliation: School of Surgery, Unité Institut National de la Santé et de la Recherche Médicale 1116, Université de Lorraine, Nancy, France.
authors.forename: Frederique
authors.initials: F
authors.lastname: Groubatch
authors.affiliation: Medical Imaging, Centre Hospitalier Universitaire-Nancy, Nancy, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Gu
authors.affiliation: School of Surgery, Unité Institut National de la Santé et de la Recherche Médicale 1116, Université de Lorraine, Nancy, France; Medical Imaging, Centre Hospitalier Universitaire-Nancy, Nancy, France.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Marie
authors.affiliation: School of Surgery, Unité Institut National de la Santé et de la Recherche Médicale 1116, Université de Lorraine, Nancy, France.
authors.forename: Nguyen
authors.initials: N
authors.lastname: Tran
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D016027:Heart Transplantation; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D016042:Transplantation, Heterotopic; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology* / Q000601:surgery*; D020257:Ventricular Remodeling