Using advanced technology, the determinants of crossbridge kinetics, force development and chemo-mechanical transduction will be studied in rat trabecular muscle. A model of chronic heart failure secondary to myocardial infarction will be studied. This will be correlated with findings from controls and rats which have been forced, with the induction of hypothyroidism, to express slow myosir isoforms. These studies should provide significant new insights into the fundamental derangements in myofilament function in heart failure. In addition to the wide range of fundamental concepts and controversies regarding contemporary theories of the mechanisms of muscle contraction, the applicant will need to develop a high level of familiarity with the principles of scientific measurement using the complex technology employed in Dr. de Tombe's laboratory.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL003255-04
Application #
2750246
Study Section
Research Training Review Committee (RTR)
Project Start
1995-08-01
Project End
2000-07-31
Budget Start
1998-08-10
Budget End
1999-07-31
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106
Wannenburg, T; Khan, A S; Sane, D C et al. (2001) Growth hormone reverses age-related cardiac myofilament dysfunction in rats. Am J Physiol Heart Circ Physiol 281:H915-22
Wannenburg, T; Heijne, G H; Geerdink, J H et al. (2000) Cross-bridge kinetics in rat myocardium: effect of sarcomere length and calcium activation. Am J Physiol Heart Circ Physiol 279:H779-90
de Tombe, P P (1998) Altered contractile function in heart failure. Cardiovasc Res 37:367-80
Fan, D; Wannenburg, T; de Tombe, P P (1997) Decreased myocyte tension development and calcium responsiveness in rat right ventricular pressure overload. Circulation 95:2312-7
Wannenburg, T; Janssen, P M; Fan, D et al. (1997) The Frank-Starling mechanism is not mediated by changes in rate of cross-bridge detachment. Am J Physiol 273:H2428-35