title: Transgenic alpha1A-adrenergic activation limits post-infarct ventricular remodeling and dysfunction and improves survival.
abstract: OBJECTIVE
  Myocardial contractility is enhanced in transgenic (TG) mice with cardiac-restricted overexpression of the alpha1A-adrenergic receptors (alpha1A-AR). We tested the hypothesis that this enhanced inotropy protects against dysfunction and remodeling after myocardial infarction (MI).
  
  
  METHODS
  We subjected alpha1A-TG and non-TG mice (NTG) to MI and determined changes in left ventricular (LV) function and diastolic dimension (LVDd) by echocardiography prior to and at 1, 3, 7, 12 and 15 weeks thereafter.
  
  
  RESULTS
  Although infarct size was similar in the NTG and alpha1A-TG groups (32+/-2 vs. 29+/-2% of LV, P=NS), mortality due to heart failure was lower after MI in the alpha1A-TG (37%, n=39) than that in the NTG animals (63%, n=56, P=0.026). NTG and alpha1A-TG mice showed similar reductions in LV fractional shortening (FS) and increases in LVDd at week-1 after MI. However, whereas NTG mice showed continuous deterioration over a 15-week period after MI in FS (fell by 40%, from 30+/-2 to 18+/-1%, P<0.01) and LVDd (increased by 24%, from 4.2+/-0.1 to 5.2+/-0.1 mm, P<0.01), the changes in both FS (fell by 14%, from 42+/-2 to 36+/-2%) and LVDd (increased by 8%, from 3.8+/-0.1 to 4.1+/-0.1 mm, both changes P<0.01 vs. NTG) were significantly less severe in the alpha1A-TG mice and did not progress after 3 weeks. At 15 weeks after MI, LV catheterization revealed better preservation of dP/dtmax in the alpha1A-TG vs. NTG mice (7270+/-324, vs. 5938+/-372 mmHg/s, P<0.05).
  
  
  CONCLUSIONS
  Enhanced inotropy resulting from transgenic overexpression of alpha1A-AR is well maintained chronically after MI and limits echocardiography-determined LV remodeling, preserves function, and reduces acute heart failure death.
authors.affiliation: Experimental Cardiology Laboratory, Baker Heart Research Institute, and Alfred Heart Centre, Alfred Hospital, Melbourne, Australia. xiaojun.du@baker.edu.au
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Du
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Gao
authors.forename: Helen
authors.initials: H
authors.lastname: Kiriazis
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Moore
authors.forename: Ziqiu
authors.initials: Z
authors.lastname: Ming
authors.forename: Yidan
authors.initials: Y
authors.lastname: Su
authors.forename: Angela M
authors.initials: AM
authors.lastname: Finch
authors.forename: Ross A
authors.initials: RA
authors.lastname: Hannan
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Dart
authors.forename: Robert M
authors.initials: RM
authors.lastname: Graham
mesh_terms: D000199:Actins / Q000032:analysis; D000375:Aging; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000032:analysis; D003094:Collagen / Q000032:analysis; D004452:Echocardiography; D005260:Female; D005353:Fibronectins / Q000032:analysis; D006333:Heart Failure / Q000378:metabolism / Q000401:mortality; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000032:analysis; D024501:Nonmuscle Myosin Type IIB / Q000032:analysis; D011897:Random Allocation; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000378:metabolism; D020257:Ventricular Remodeling
chemical_list: D000199:Actins; C547714:Adra1a protein, mouse; D005353:Fibronectins; D018340:Receptors, Adrenergic, alpha-1; D009320:Atrial Natriuretic Factor; D003094:Collagen; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains; D006909:Hydroxyproline