Endurance exercise is cardioprotective against ischemia-reperfusion (I-R) injury. Previously identified mediators of cardioprotection include antioxidants, antioxidant enzymes, heat shock proteins, and iNOS suggesting that exercise-induced cardioprotection is a polygenic phenomenon. Recent data demonstrate that the inducible form of cyclooxygenase (COX-2), and subsequent prostanoid production (PGE2 and PGI2), is cardioprotective. Data from our laboratory indicate that COX-2 activity is dramatically increased in exercise trained rats. The cardioprotective impact of an exercise-induced increase in COX-2 activity, however, is unknown. The objective of this proposal is to elucidate the effects of endurance exercise on COX-2-mediated cardioprotection. The applicant will test the hypothesis that exercise-mediated cardioprotection against I-R myocardial stunning and infarction is dependent upon increased myocardial COX-2 activity and its prostanoid metabolites. Exercise mediated cardioprotection in rats will be evaluated in response to stunning and infarction insults. An I-R stunning challenge will be performed using the isolated working heart model while I-R infarction will be performed in vivo. In both models, COX-2 activity will be blocked by selective pharmacological inhibitors. Measures of myocardial performance will be used as correlates to markers of COX-2 activity and myocardial damage. This project should produce important new insights into mechanisms exercise-induced cardioprotection in addition to the role of COX-2 in general cardiac pathophysiology. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL074666-02
Application #
6779150
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Commarato, Michael
Project Start
2003-07-07
Project End
2005-07-06
Budget Start
2004-07-07
Budget End
2005-07-06
Support Year
2
Fiscal Year
2004
Total Cost
$47,296
Indirect Cost
Name
University of Florida
Department
Other Health Professions
Type
Other Domestic Higher Education
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Quindry, John C; French, Joel; Hamilton, Karyn L et al. (2010) Exercise does not increase cyclooxygenase-2 myocardial levels in young or senescent hearts. J Physiol Sci 60:181-6
Quindry, John C; Hamilton, Karyn L; French, Joel P et al. (2007) Exercise-induced HSP-72 elevation and cardioprotection against infarct and apoptosis. J Appl Physiol 103:1056-62