Myocardial blood flow and myocardial uptake of 201Tl and 99mTc-sestamibi during coronary vasodilation induced by CGS-21680, a selective adenosine A2A receptor agonist

Background-We investigated the hemodynamic and coronary vasodilatory effects of CGS-21680, a potent selective adenosine A(2A) agonist, as well as its potential use as a new stress modality in combination with perfusion scintigraphy, Methods and Results-A stenosis of the left anterior descending coronary artery (LAD) was produced in dogs to reduce the reactive hyperemic response to <20%. Adenosine and CGS-21680 were then separately infused to maximize left circumflex coronary artery (LCx) flow velocity. Tl-201 (0.5 mCi) and Tc-99m-sestamibi (5 mCi) were injected at the maximal dose of CGS-21680. Heart rate decreased with adenosine but increased during CGS-21680 infusion (P<0.005). The decrease in systolic blood pressure was more prominent with adenosine than with CGS-21680 (P<0.005). In the control LCx zone, maximal myocardial blood Row (MBF) (measured by radioactive microspheres) increased 3.1-fold during adenosine infusion (P<0.005) and 3.8-fold during CGS-21680 infusion (P<0.005). In the stenotic LAD zone, MBF did not change significantly. During adenosine and CGS-21680 infusion, stenosis/control zone MBF ratios were comparable (0.32+/-0.11 versus 0.27+/-0.10, P=NS), and transmural Tl-201 and Tc-99m-sestamibi count-activity ratios (0.48 +/-0.11 and 0.51 +/-0.09, respectively) were also comparable (P=NS). Myocardial scintigraphy uncovered perfusion defects in all dogs. Conclusions-CGS-21680 elicits coronary vasodilation comparable to that of adenosine and produces profound heterogeneity of MBF and of Tl-201 and Tc-99m-sestamibi myocardial uptake, rendering it a promising agent for pharmacological myocardial perfusion imaging.