In the United States, cardiovascular disease is a leading cause of death and disability among people 65 years of age or older. There is an age- related decline in myocardial mechanical function that in men, can be ameliorated by exercise training. The mechanisms responsible for the decrease in mechanical function are poorly understood. Results of studies in experimental models of aging suggest that abnormalities in myocardial perfusion and intermediary metabolism may contribute to the decline in mechanical function. However, whether these observations are applicable to human aging is unknown. Our hypothesis is that with aging there is a decline in myocardial perfusion reserve and oxygen consumption and a shift in myocardial intermediary metabolism to a greater reliance on glucose utilization to support overall oxidative metabolism which together impairs systolic function particularly when there is an increased demand in myocardial work. Furthermore, we hypothesize that endurance exercise training in aged men will improve myocardial perfusion reserve and intermediary metabolism which in turn will have salutary effects on myocardial mechanical function particularly when myocardial work is increased. We will provide or disprove this hypothesis by addressing the following specific aims: 1. To determine in humans, the impact of aging on myocardial perfusion and intermediary metabolism, at rest and during pharmacological stress, as they related to changes in mechanical function at rest, during exercise and during pharmacological stress: 2. To determine in aged humans, the impact of endurance exercise training on myocardial perfusion and intermediary metabolism, at rest and during pharmacological stress as they relate to changes in mechanical function (at rest, during exercise and during pharmacological stress) and whether the impact of exercise training is related to gender. This research will further our understanding of the effects of aging on myocardial perfusion and intermediary metabolism as they relate to myocardial mechanical function in humans. Demonstration that myocardial perfusion and intermediary metabolism can be modified by endurance exercise training with subsequent salutory effects on myocardial function will provide a therapeutic strategy designed to improve left ventricular function or at least slow the progression of left ventricular dysfunction that occurs with aging.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG015466-04
Application #
6372197
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Rossi, Winifred K
Project Start
1998-05-01
Project End
2003-03-31
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
4
Fiscal Year
2001
Total Cost
$538,247
Indirect Cost
Name
Washington University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
McGill, Janet B; Peterson, Linda R; Herrero, Pilar et al. (2011) Potentiation of abnormalities in myocardial metabolism with the development of diabetes in women with obesity and insulin resistance. J Nucl Cardiol 18:421-9; quiz 432-3
Peterson, Linda R; Soto, Pablo F; Herrero, Pilar et al. (2008) Impact of gender on the myocardial metabolic response to obesity. JACC Cardiovasc Imaging 1:424-33
Gropler, Robert J (2008) Molecular imaging will replace myocardial perfusion imaging. J Nucl Cardiol 15:429-34
Saeed, Ibrahim M; Barry, Michael; Peterson, Linda R et al. (2007) Positron emission tomography imaging in the cardiometabolic syndrome. J Cardiometab Syndr 2:67-9
Peterson, Linda R; Soto, Pablo F; Herrero, Pilar et al. (2007) Sex differences in myocardial oxygen and glucose metabolism. J Nucl Cardiol 14:573-81
de las Fuentes, Lisa; Brown, Angela L; Mathews, Santhosh J et al. (2007) Metabolic syndrome is associated with abnormal left ventricular diastolic function independent of left ventricular mass. Eur Heart J 28:553-9
Cresci, Sharon; Gropler, Robert J (2007) Image-guided cardiovascular functional genomics: finding the needle in the haystack. J Nucl Cardiol 14:275-6
de las Fuentes, Lisa; Soto, Pablo F; Cupps, Brian P et al. (2006) Hypertensive left ventricular hypertrophy is associated with abnormal myocardial fatty acid metabolism and myocardial efficiency. J Nucl Cardiol 13:369-77
Herrero, Pilar; Peterson, Linda R; McGill, Janet B et al. (2006) Increased myocardial fatty acid metabolism in patients with type 1 diabetes mellitus. J Am Coll Cardiol 47:598-604
Srinivasan, Muthayyah; Herrero, Pilar; McGill, Janet B et al. (2005) The effects of plasma insulin and glucose on myocardial blood flow in patients with type 1 diabetes mellitus. J Am Coll Cardiol 46:42-8

Showing the most recent 10 out of 17 publications