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 μg/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-ani- mal coefficient of variation (100 Ö 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.
All Science Journal Classification (ASJC) codes
- Coronary blood flow
- Cyclic adenosine monophosphate
- β-Adrenergic agonist