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.
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.


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.
He
Z X
ZX
Section of Cardiology, Baylor College of Medicine/Methodist Hospital, Houston, Tex, USA.
Cwajg
E
E
Hwang
W
W
Hartley
C J
CJ
Funk
E
E
Michael
L H
LH
Verani
M S
MS
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D009200:Myocardial Contraction / Q000187:drug effects*; D010627:Phenethylamines / Q000494:pharmacology*; D058906:Purinergic P1 Receptor Agonists; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D017256:Technetium Tc 99m Sestamibi / Q000494:pharmacology*; D013793:Thallium / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D019275:Radiopharmaceuticals; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C027549:thallium chloride; D017256:Technetium Tc 99m Sestamibi; D013793:Thallium; D000241:Adenosine