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.
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