Pablo F. Soto, M.D.

DEPARTMENT OF Internal Medicine
Keywords: cardiac disease, cardiovascular imaging, metabolism, PET, estrogen, gender

Normal myocardial metabolism is altered significantly with aging and in a variety of cardiovascular disorders including hypertension, LVH, heart failure and diabetes. The overall interest of our lab is to use non-invasive imaging techniques to assess the impact of altered metabolism on heart function. To this end, we are investigating differences between sexes and the effects of aging on heart metabolism at baseline and with a variety of interventions. Our research currently consists of the following projects:

1.) Pre-menopausal females have a lower incidence of heart failure in comparison to age matched males yet this advantage disappears post-menopause. Given that estrogen has been shown to increase glucose utilization in skeletal muscle, one of our goals is to discover the effects of estrogen on myocardial substrate use. To achieve this goal, post-menopausal women are undergoing short term hormone replacement therapy and myocardial metabolic and functional data are being collected both at baseline and post-therapy with PET and echo, respectively.

2.) Age-related changes in myocardial metabolism may be related to a decline in endothelial function and the resultant loss in nitric oxide (NO) production seen in older individuals. In order to investigate the mechanism of these age-related changes, we are administering L-NAME (an NO inhibitor) and L-arginine, (to stimulate NO production) to young and older individuals to assess the metabolic and functional impact of these interventions.

3.) PPARa may also play a role in the regulation of myocardial substrate metabolism in humans. The effects of PPARa on aging are being investigated in before and after the administration of fenofibrate, a strong PPARa agonist, to both young and older individuals.

Findings from these studies may shed light on the mechanisms involved in the regulation of myocardial metabolism which in turn may lead to novel metabolic therapy for a variety of cardiovascular disorders.