Studies of inotropic function in healthy elderly have generally shown preservation of contractile parameters during basal conditions, but alterations in function occur with stress, as in the cardiac response to exercise, when compared to younger controls. In vitro studies of cardiac function in aged animals have also shown a diminished response to sympathetic stimulation. Adenosine is a nucleoside with negative chronotropic, dromotropic, and inotropic properties, and it appears to facilitate feedback inhibition of cardiac contractility in the face of increased metabolic demand (e.g., hypoxia or sympathetic stimulation). In rat heart, isoproterenol administration results in a greater release of adenosine in mature adults compared to young adults. Therefore, increased endogenous adenosine production or altered receptor sensitivity may limit increases in contractility or heart rate in senescence. In addition to clinical and teaching responsibilities, the role of adenosine in cardiac senescence will be investigated in animals and humans as follows: Studies of Adenosine Production and Receptor Sensitivity in F344 Rat: Ongoing studies of adenosine regulation of cardiac function in senescence will continue, utilizing isolated cardiac muscle and Langendorff preparations. Emphasis of study will be on adenosine production and receptor sensitivity, and the relation of these to cardiac muscle metabolism. Study of Age-Related Cardiac Response to Theophylline in Man: Preliminary studies suggest an increased inotropic response to theophylline in elderly men compared to younger men. Theophylline's cardiac effects are mediated by several mechanisms, including antagonism of the binding of extracellular adenosine at cell-surface receptors. Theophylline will be administered acutely and chronically to healthy young, middle-aged, and elderly men and women. Non-invasive measures of cardiac function will be attained before and during autonomic blockade. Therefore, the influence of sympathetic stimulation and of adenosine antagonism on cardiac function may be determined. Clinical/Teaching: The P.I. will help set up an outpatient urinary incontinence clinic in the Boise VA Medical Center, will participate in outpatient and inpatient geriatric consultation, and will have teaching responsibilities for medical students, residents, and fellows.
| Montamat, S C; Olson, R D; Mudumbi, R V et al. (1996) Age-related characterization of atrial adenosine A1 receptor activation: direct effects on chronotropic and inotropic function in the Fischer 344 rat. J Gerontol A Biol Sci Med Sci 51:B239-46 |
| Mudumbi, R V; Olson, R D; Hubler, B E et al. (1995) Age-related effects in rabbit hearts of N6-R-phenylisopropyladenosine, an adenosine A1 receptor agonist. J Gerontol A Biol Sci Med Sci 50:B351-7 |
| Mudumbi, R V; Montamat, S C; Bruns, R F et al. (1993) Cardiac functional responses to adenosine by PD 81,723, an allosteric enhancer of the adenosine A1 receptor. Am J Physiol 264:H1017-22 |
