title: Increasing cardiac contractility after myocardial infarction exacerbates cardiac injury and pump dysfunction.
abstract: BACKGROUND
  Myocardial infarction (MI) leads to heart failure (HF) and premature death. The respective roles of myocyte death and depressed myocyte contractility in the induction of HF after MI have not been clearly defined and are the focus of this study.
  
  
  OBJECTIVE
  We developed a mouse model in which we could prevent depressed myocyte contractility after MI and used it to test the idea that preventing depression of myocyte Ca(2+)-handling defects could avert post-MI cardiac pump dysfunction.
  
  
  RESULTS
  MI was produced in mice with inducible, cardiac-specific expression of the β2a subunit of the L-type Ca(2+) channel. Myocyte and cardiac function were compared in control and β2a animals before and after MI. β2a myocytes had increased Ca(2+) current; sarcoplasmic reticulum Ca(2+) load, contraction and Ca(2+) transients (versus controls), and β2a hearts had increased performance before MI. After MI, cardiac function decreased. However, ventricular dilation, myocyte hypertrophy and death, and depressed cardiac pump function were greater in β2a versus control hearts after MI. β2a animals also had poorer survival after MI. Myocytes isolated from β2a hearts after MI did not develop depressed Ca(2+) handling, and Ca(2+) current, contractions, and Ca(2+) transients were still above control levels (before MI).
  
  
  CONCLUSIONS
  Maintaining myocyte contractility after MI, by increasing Ca(2+) influx, depresses rather than improves cardiac pump function after MI by reducing myocyte number.
authors.affiliation: Temple University, School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Chen
authors.forename: Erhe
authors.initials: E
authors.lastname: Gao
authors.forename: Scott M
authors.initials: SM
authors.lastname: MacDonnell
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Mikhail
authors.initials: M
authors.lastname: Kolpakov
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakayama
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
authors.forename: Naser
authors.initials: N
authors.lastname: Jaleel
authors.forename: David M
authors.initials: DM
authors.lastname: Harris
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Li
authors.forename: Mingxin
authors.initials: M
authors.lastname: Tang
authors.forename: Remus
authors.initials: R
authors.lastname: Berretta
authors.forename: Annarosa
authors.initials: A
authors.lastname: Leri
authors.forename: Jan
authors.initials: J
authors.lastname: Kajstura
authors.forename: Abdelkarim
authors.initials: A
authors.lastname: Sabri
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Koch
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Molkentin
authors.forename: Steven R
authors.initials: SR
authors.lastname: Houser
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020013:Calcium Signaling / Q000235:genetics; D002478:Cells, Cultured; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000235:genetics / Q000502:physiology*; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology / Q000502:physiology
chemical_list: C514350:CACNA1C protein, mouse; D020746:Calcium Channels, L-Type