Effect of isoproterenol on the relationship between regional cyclic AMP and local coronary blood flow in the canine myocardium.

This study was designed to test in the dog heart the hypothesis that local levels of myocardial cyclic AMP (cAMP) would exhibit significant heterogeneity; that this heterogeneity would correlate with local coronary blood flow, and that this association would be increased with isoproterenol stimulation. Anesthetized open-chest dogs were studied during control (n = 7) or isoproterenol (0.5 micrograms/kg/min) infusion (n = 7) to test this hypothesis. Coronary blood flow was measured with radioactive microspheres, and cAMP was determined with a competitive binding assay using 3H-cAMP. Significant heterogeneity in cAMP existed during basal [592 pmol/g, within-animal coefficient of variation (100 x mean/SD) = 45.2%] and isoproterenol stimulated [872 (27.3%)] conditions. Method variability could account for only 28% of the total basal variability. No correlation between local blood flow [87 ml/min/100 g (12.9%)] and local cAMP was found under control conditions. Both coronary blood flow [206 (20.8%)] and cAMP levels increased significantly with isoproterenol stimulation. There was a significant correlation between normalized stimulated blood flow and cAMP: % flow = 0.39 (% cAMP) + 61.3 (r = 0.48, p < 0.0001). We conclude that significant heterogeneity in myocardial cAMP levels exists, and that this heterogeneity correlates with coronary blood flow heterogeneity during isoproterenol stimulation.