Myocardial Blood Flow and Myocardial Uptake of 201 Tl and 99m Tc-Sestamibi During Coronary Vasodilation Induced by CGS-21680, a Selective Adenosine A 2A Receptor Agonist

Abstract

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. 201 Tl (0.5 mCi) and 99m Tc-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 flow (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 201 Tl and 99m Tc-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 201 Tl and 99m Tc-sestamibi myocardial uptake, rendering it a promising agent for pharmacological myocardial perfusion imaging.