The hypothesis considers that endogenously released adenosine functions as a physiological regulator of adrenergic influences on myocardial contractile performance. The hypothesis also considers that adenosine's modulator role also extends to other naturally occurring compounds such as glucagon and histamine and that the inhibitory effect of adenosine on contractile performance is increased with increasing adenylate cyclase activity. It is hypothesized that the extent of these modulatory influences of adenosine changes during maturation and aging partly because the magnitude of the inotropic responses to adrenergic and other stimuli changes between youth and old age and partly because the basal inotropic action of adenosine varies with age. It is further hypothesized that, in all probability, the main effects of adenosine are mediated through interactions with a specific adenosine receptor located on the myocardial cell surface. To assess comparative performance of atrial and ventricular muscles during maturation and aging we will use atrial trabeculae and ventricular papillary muscles isolated from the hearts of ferrets 6 weeks, 12 weeks, 24 weeks and 120 to 180 weeks of age. The muscles are studied in a myograph capable of determining the mechanical characteristics of a central segment thus eliminating contamination in data collection due to damaged ends. Dose-response curves to adenosine will be performed in catecholamine depleted muscles and after muscarinic blockade. We will determine age-dependent inotropic responses of atrial and ventricular muscle to glucagon, histamine, alpha-adenoceptor and beta-adrenoceptor stimulations both in the presence and absence of adenosine. We will compare the relative potency of adenosine, adenosine analogues and adenosine antagonists during maturation and aging and we will examine whether naturally occurring adenosine influences contractile performance by studying the inotropic responses of cardiac muscle to isuprel, glucagon and histamine in the presence of dipyridamole, in the presence of adenosine deaminase inhibitors and in the presence of adenosine deaminase inhibitors and dipyridamole. The powerful modulatory effect of adenosine on positive inotropic stimuli might represent an important feedback mechanism designed to preserve energy stores.
| Urthaler, F; Walker, A A; Reeves, R C et al. (1989) Effects of ryanodine on contractile performance of intact length-clamped papillary muscle. Circ Res 65:1270-82 |
| Urthaler, F; Walker, A A; Reeves, D N et al. (1988) Maximal twitch tension in intact length-clamped ferret papillary muscles evoked by modified postextrasystolic potentiation. Circ Res 62:65-74 |
