Over one-half million cardiac surgical procedures are performed in the United States alone and a large number of these procedures require cardiopulmonary bypass and cardioplegic arrest. However, transient left ventricular (LV) dysfunction can occur with reperfusion and separation from cardiopulmonary bypass and result in a complex post-operative course. During this past funding period, this laboratory demonstrated that contractile dysfunction and reduced inotropic capacity occurred following cardioplegic arrest and rewarming. One of the more potent bioactive peptides released into the systemic vasculature under these conditions is endothelin-1 (ET). Increased synthesis and release of ET has been implicated to exacerbate LV pump dysfunction in a number of cardiovascular diseases. Thus, elevated ET in patients during and following cardiac surgery may compromise LV function and contribute to a complex post-operative course. The central hypothesis of this continuing research program is that increased local myocyte synthesis and release of ET occurs during and following cardioplegic arrest and cardiopulmonary bypass causing chronic activation of the myocyte ET/A receptor and thereby is an upstream event which directly contributes to LV contractile dysfunction in the early post-cardiac surgical period. This project will perform an integrated series of studies which will identify the cellular and molecular basis by which ET contributes to contractile dysfunction following cardioplegic arrest and then translate these basic findings to an in-vivo model. The specific role of ET receptor activation and the potential benefit of ET blockade in the postcardioplegic setting will be determined. This project will perform the first direct in-vivo measurements of ET myocardial dynamics in patients undergoing cardioplegic arrest which will set the stage for future interventional studies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL056603-06
Application #
6621169
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Massicot-Fisher, Judith
Project Start
1997-04-01
Project End
2005-11-30
Budget Start
2003-02-01
Budget End
2003-11-30
Support Year
6
Fiscal Year
2003
Total Cost
$321,750
Indirect Cost
Name
Medical University of South Carolina
Department
Surgery
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
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