title: Short-term mechanical unloading with left ventricular assist devices after acute myocardial infarction conserves calcium cycling and improves heart function.
abstract: OBJECTIVE
  This study sought to demonstrate that short-term cardiac unloading with a left ventricular (LV) assist device (LVAD) after acute myocardial infarction (MI) can conserve calcium cycling and improve heart function.
  
  
  BACKGROUND
  Heart failure secondary to MI remains a major source of morbidity and mortality. Alterations in calcium cycling are linked to cardiac dysfunction in the failing heart.
  
  
  METHODS
  Adult Dorsett hybrid sheep underwent acute MI and were mechanically unloaded with an axial-flow LVAD (Impella 5.0) for 2 weeks (n = 6). Six sheep with MI only and 4 sham sheep were used as controls. All animals were followed for 12 weeks post-MI. Regional strains in the LV were measured by sonomicrometry. Major calcium-handling proteins (CHPs), including sarco-/endoplasmic reticulum calcium ATPase-2α (SERCA-2α), Na(+)-Ca(2+) exchanger-1, and phospholamban, and Ca(2+)-ATPase activity were investigated. The electrophysiological calcium cycling in single isolated cardiomyocytes was measured with the patch-clamp technique. The related ultrastructures were studied with electron microscopy.
  
  
  RESULTS
  LVAD unloading alleviated LV dilation and improved global cardiac function and regional contractility compared with the MI group. The regional myocardial strain (stretch) was minimized during the unloading period and even attenuated compared with the MI group at 12 weeks. Impaired calcium cycling was evident in the adjacent noninfarcted zone in the MI group, whereas CHP expression was normalized and Ca(2+)-ATPase activity was preserved in the LVAD unloading group. The electrophysiological calcium cycling was also conserved, and the ultrastructural damage was ameliorated in the unloaded animals.
  
  
  CONCLUSIONS
  Short-term LVAD unloading may conserve calcium cycling and improve heart function during the post-infarct period.
authors.affiliation: Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland21201, USA.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Wei
authors.forename: Tieluo
authors.initials: T
authors.lastname: Li
authors.forename: Brian
authors.initials: B
authors.lastname: Hagen
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.forename: Pablo G
authors.initials: PG
authors.lastname: Sanchez
authors.forename: Katrina
authors.initials: K
authors.lastname: Williams
authors.forename: Shuying
authors.initials: S
authors.lastname: Li
authors.forename: Giacomo
authors.initials: G
authors.lastname: Bianchi
authors.forename: Ho Sung
authors.initials: HS
authors.lastname: Son
authors.forename: Changfu
authors.initials: C
authors.lastname: Wu
authors.forename: Christopher
authors.initials: C
authors.lastname: DeFilippi
authors.forename: Kai
authors.initials: K
authors.lastname: Xu
authors.forename: William J
authors.initials: WJ
authors.lastname: Lederer
authors.forename: Zhongjun J
authors.initials: ZJ
authors.lastname: Wu
authors.forename: Bartley P
authors.initials: BP
authors.lastname: Griffith
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D006353:Heart-Assist Devices; D008854:Microscopy, Electron; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011474:Prosthesis Design; D020127:Recovery of Function; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D012756:Sheep; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D013997:Time Factors; D014463:Ultrasonography; D016277:Ventricular Function, Left; D017725:Ventricular Pressure; D020257:Ventricular Remodeling; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger; D000099211:Phospholamban