A series of studies are proposed in chronically instrumented, conscious animals to define and contrast systolic performance in the normal right ventricle with systolic performance in the right ventricle failing due to pressure overload from reversible pulmonary stenosis, volume overload from tricuspid regurgitation, and rate overload from pacing-induced cardiomyopathy. Studies will employ this laboratory's unique experience in chronic animal instrumentation, along with two-dimensional echocardiography, three-dimensional (3-D) sonomicrometry, and state of the art, real time, 3-D echocardiography. Right ventricular function will be assessed using the load-insensitive Frank-Starling relationship and the end-systolic pressure-volume relationship. Several hypotheses will be tested regarding abnormal geometry of contraction in the failing right ventricle, the importance of myocardial creep during development of right ventricular failure, the interaction between right ventricular contractility and diastolic properties in the normal versus failing right ventricle, the effects of afterload upon right ventricular systolic function, interaction between right ventricular dysfunction and left ventricular contractility during right ventricular failure, and the influence of the pericardium upon right ventricular dysfunction. These studies should provide a foundation for understanding the pathophysiology of right ventricular failure and suggest more effective management for right ventricular failure, such as aggressive and early treatment of functional tricuspid regurgitation, right ventricular afterload reduction, and short-term inotropic therapy to obtain long-term benefits in patients with right ventricular failure.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL056227-03
Application #
6056349
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1997-09-15
Project End
2001-08-31
Budget Start
1999-09-01
Budget End
2001-08-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Duke University
Department
Surgery
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Shah, A S; Atkins, B Z; Hata, J A et al. (2000) Early effects of right ventricular volume overload on ventricular performance and beta-adrenergic signaling. J Thorac Cardiovasc Surg 120:342-9