Submitted on February 11, 2008
Revised on April 27, 2008
Accepted on May 27, 2008
Cardiac Dysfunction in Aging Conscious Rats: Altered Cardiac Cytoskeletal Proteins as a Potential Mechanism
Samuel C Lieber1, Hongyu Qiu2, Li Chen3, You-Tang Shen4, Chull Hong5, William C Hunter6, Nadine Aubry, Stephen F. Vatner2, and Dorothy E. Vatner5*
1 University of Medicine and Dentistry of New Jersey ? New Jersey Medical School
2 University of Medicine and Dentistry of New Jersey, New Jersey Medical School
3 University of Medicine & Dentistry of New Jersey
4 University of Medicine and Dentistry of New Jersey-New Jersey Medical School
5 UMDNJ - New Jersey Medical School
6 NJIT New Jersey's Science and Technology University
* To whom correspondence should be addressed. E-mail: vatnerdo{at}umdnj.edu.
The objective of this study was to test the hypothesis that the mechanism mediating left ventricular (LV) dysfunction in the aging rat heart involves, in part, changes in cardiac cytoskeletal components. Our results show that there were no significant differences in heart rate, LV pressure or LV diameter between conscious, instrumented young [5.9±0.3 months (n=9)] and old [30.6±0.1 months (n=10)] rats. However, LV dP/dt was reduced, p<0.05, (8,309±790 vs. 11,106±555 mmHg/sec) and isovolumic relaxation time (
) was increased (p<0.05) (8.7±0.7 vs. 6.3±0.6 msec) in old vs. young rats, respectively. The differences in baseline LV function in young and old rats, which were modest, were accentuated after 
-adrenergic receptor stimulation with dobutamine (20 µg/kg), which increased LV dP/dt by 170±9% in young rats, significantly more, p<0.05, then observed in old rats, 115±5%. Volume loading in anesthetized rats demonstrated significantly impaired LV compliance in old rats, as measured by the LV end-diastolic pressure and dimension relationship. In old rat hearts, there was a significant, p<0.05, increase in the percentage of LV collagen (2.4±0.2% vs. 1.3±0.2%), 
-tubulin (92%) and -tubulin (2.3-fold), while intact desmin decreased by 51%. Thus, the cardiomyopathy of aging in old, conscious rats may be due not only to increases in collagen, but also to alterations in cytoskeletal proteins.
