title: Effects of environmental stress following myocardial infarction on behavioral measures and heart failure progression: The influence of isolated and group housing conditions.
abstract: BACKGROUND
  Heart failure (HF) prognosis is negatively influenced by adverse environmental conditions associated with psychological distress and depression. The underlying mechanisms are not well understood because of insufficient experimental control in prior clinical and epidemiological studies. Using a validated animal model we examined whether distress-producing environmental manipulations (social isolation and crowding) increase HF progression following myocardial infarction (MI).
  
  
  METHODS
  MI was induced using coronary artery ligation in 8-week old male Wistar rats (N=52) and results were compared to sham surgery (N=24). Housing conditions were randomly assigned at 5 days post MI or sham surgery (1/cage=isolation, 2/cage=standard reference condition, or 4/cage=crowding) and continued for 17 weeks until the end of observation. The open field test was used to test behavioral responses. Echocardiograms were obtained at weeks 8 and 16, and left ventricular (LV) weight at week 17.
  
  
  RESULTS
  Housing conditions increased behavioral markers of distress (p=0.046) with the strongest effects for the isolated (1/cage) (p=0.022). MI did not increase distress-related behaviors compared to sham. MI-surgery resulted in characteristic HF indices (left ventricular ejection fraction (LVEF) at week 16=46 ± 12% vs. 80 ± 7% in sham, p<0.001). Housing condition was not related to LVEF or LV weight (p>0.10).
  
  
  CONCLUSIONS
  Adverse environmental conditions, particularly isolated housing, produce increases in some of the behavioral indicators of distress. No effects of housing were found on post-MI progression of HF. The distress-HF associations observed in humans may therefore reflect common underlying factors rather than an independent causal pathway. Stronger environmental challenges may be needed in future animal research examining distress as related HF progression.
authors.affiliation: Department of Medicine, Division of Cardiology, University of Maryland, Baltimore, MD, USA; Department of Medical and Clinical Psychology, Center of Research on Psychology in Somatic diseases (CoRPS), Tilburg University, Tilburg, The Netherlands.
authors.forename: Willem J
authors.initials: WJ
authors.lastname: Kop
authors.affiliation: Department of Medicine, Division of Cardiology, University of Maryland, Baltimore, MD, USA; Intensive Care Unit, Hospital Israelita Albert Einstein, Sao Paulo, Brazil;
authors.forename: Tatiana F
authors.initials: TF
authors.lastname: Galvao
authors.affiliation: Department of Medicine, Division of Cardiology, University of Maryland, Baltimore, MD, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Synowski
authors.affiliation: Department of Medicine, Division of Cardiology, University of Maryland, Baltimore, MD, USA.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Psychiatry, University of Maryland, Baltimore, MD, USA.
authors.forename: Adem
authors.initials: A
authors.lastname: Can
authors.affiliation: Department of Medicine, Division of Cardiology, University of Maryland, Baltimore, MD, USA; Department of Medicine, New York University, New York, NY, USA.
authors.forename: Karen M
authors.initials: KM
authors.lastname: O'Shea
authors.affiliation: Department of Psychiatry, University of Maryland, Baltimore, MD, USA; Department of Pharmacology, University of Maryland, Baltimore, MD, USA; Department of Anatomy and Neurobiology, University of Maryland, Baltimore, MD, USA.
authors.forename: Todd D
authors.initials: TD
authors.lastname: Gould
authors.affiliation: Department of Medicine, Division of Cardiology, University of Maryland, Baltimore, MD, USA; Department of Physiology, School of Medical Sciences, The University of Sydney, Sydney, Australia. Electronic address: w.j.kop@uvt.nl.
authors.forename: William C
authors.initials: WC
authors.lastname: Stanley
mesh_terms: D000818:Animals; D003441:Crowding / Q000523:psychology; D004195:Disease Models, Animal; D004452:Echocardiography; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology* / Q000523:psychology; D006799:Housing, Animal; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000503:physiopathology* / Q000523:psychology; D011897:Random Allocation; D017208:Rats, Wistar; D012934:Social Isolation / Q000523:psychology; D013315:Stress, Psychological / Q000150:complications / Q000503:physiopathology*; D016277:Ventricular Function, Left / Q000502:physiology
keywords: Cardiac function; Heart failure; Housing conditions; Myocardial infarction; Social stress