Copyright © 2006, European Society of Cardiology
Transgenic 
1A-adrenergic activation limits post-infarct ventricular remodeling and dysfunction and improves survival
aExperimental Cardiology Laboratory, Baker Heart Research Institute, and Alfred Heart Centre, Alfred Hospital, Melbourne, Australia
bGrowth Control Laboratory, Peter MacCallum Cancer Centre and Biochemistry and Molecular Biology Department, University of Melbourne, Melbourne, Australia
cVictor Chang Cardiac Research Institute and St. Vincent Hospital, Sydney, Australia
* Corresponding author. Tel.: +61 3 85321267; fax: +61 3 85321100. Email address: xiaojun.du{at}baker.edu.au
Objective: Myocardial contractility is enhanced in transgenic (TG) mice with cardiac-restricted overexpression of the 
1A-adrenergic receptors (1A-AR). We tested the hypothesis that this enhanced inotropy protects against dysfunction and remodeling after myocardial infarction (MI).
Methods We subjected 1A-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 1A-TG groups (32±2 vs. 29±2% of LV, P=NS), mortality due to heart failure was lower after MI in the 1A-TG (37%, n=39) than that in the NTG animals (63%, n=56, P=0.026). NTG and 1A-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 1A-TG mice and did not progress after 3 weeks. At 15 weeks after MI, LV catheterization revealed better preservation of dP/dtmax in the 1A-TG vs. NTG mice (7270±324, vs. 5938±372 mmHg/s, P<0.05).
Conclusion Enhanced inotropy resulting from transgenic overexpression of 1A-AR is well maintained chronically after MI and limits echocardiography-determined LV remodeling, preserves function, and reduces acute heart failure death.
KEYWORDS 1A-adrenergic receptor; Heart failure; Ventricular remodeling
Time for primary review 16 days
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