Serial myocardial imaging with technetium-99m methoxyisobutyl isonitrile (9'Tc-MIBI) has been proposed for evaluating myocardial salvage after reperfusion. To define 'mTc-MIBI uptake before and after reperfusion, 17 open-chest dogs underwent 3 hours of left anterior descending artery occlusion and 3 hours of reperfusion. 9'Tc-MIBI was injected during occlusion (group 1) or after 90 minutes of reperfusion (group 2). Myocardial 99'Tc-MIBI activity was correlated with microsphere flow during occlusion and reperfusion. Anatomic risk area and infarct area were defined by postmortem vital staining and correlated with the perfusion defects defined by analysis of 99mTc-MIBI macroautoradiographs and gamma camera images of myocardial slices. The left ventricle was divided into 96 segments for gamma well counting. Flow and '9"Tc-MIBI activity were normalized to nonischemic values. Myocardial segments were grouped, based on occlusion flow, into zones: severely ischemic (<30% nonischemic), moderately ischemic (>30%o, .60%o nonischemic), mildly ischemic (>60%o, <90%1 nonischemic), and nonischemic (>90%o, < 120% nonischemic). Among dogs injected with "'Tc-MIBI during coronary occlusion (group 1), myocardial 99'Tc-MIBI activity correlated linearly with occlusion flow for both endocardial (r=0.91) and transmural (r=0.91) segments. The risk area defined by '9mTc-MIBI autoradiography (group 1) correlated with the postmortem risk area (p=0.94) but was 29O smaller than the anatomic risk area (p=0.03), reflecting the contribution of collateral flow. Among dogs injected with "'Tc-MIBI after reperfusion (group 2), myocardial 99"Tc-MIBI did not correlate with reperfusion flow in either endocardial or transmural segments. Among group 2 dogs, myocardial 9'Tc-MIBI activity was significantly less than reperfusion flow at the time of injection in the severely ischemic (25 ±5% versus 74±24% nonischemic,p=0.002), moderately ischemic (54±12% versus 96+15% nonischemic, p=0.001), and mildly ischemic (84±6% versus 93±3% nonischemic, p=0.002) zones. The defect area defined by 'mTc-MIBI autoradiography (group 2) correlated very closely with the postmortem infarct area (p=0.98). Thus, the myocardial uptake of 99mTc-MIBI during coronary occlusion correlates with occlusion flow and reflects the "area at risk." When 99mTc-MIBI was given after 90 minutes of reperfusion following 3 hours of coronary occlusion, the myocardial activity was significantly reduced compared with reperfusion flow in both necrotic and perinecrotic regions, reflecting myocardial viability more than the degree of reperfusion. (Circulation 1990;82:1424-1437 T X ahe current management of myocardial infarcinfarction, the extent of myocardial necrosis is detertion focuses on the application of acute mined by the "area at risk," collateral flow, and the interventional reperfusion techniques to duration of coronary occlusion.2 A noninvasive imagreduce myocardial necrosis.1 During myocardial ing technique that could 1) assess the area at risk, 2)

Thus, with adenosine-induced hyperemic flow, both 201Tl and sestamibi significantly underestimated the magnitude of the flow disparity between stenotic and normal perfusion beds. The degree of underestimation was greater for sestamibi. The clinical implication of these experimental findings for vasodilator perfusion imaging remains to be determined, since factors such as greater redistribution and scatter with 201Tl could offset its advantages.

Background-The oxidized low-density lipoprotein receptor (LDLR) LOX-1 plays a crucial role in atherosclerosis. We sought to detect and assess atherosclerotic plaque in vivo by using single-photon emission computed tomography/ computed tomography and magnetic resonance imaging and a molecular probe targeted at LOX-1. Methods and Results-Apolipoprotein E Ϫ/Ϫ mice fed a Western diet and LDLR Ϫ/Ϫ and LDLR

Adenosine and adenosine A(2A) receptor agonists have been shown to limit myocardial infarct size when given at vasodilatory doses during reperfusion. This beneficial effect is thought to be due, in part, to stimulation of adenosine A(2A) receptors on inflammatory cells. The specific aims of this study were to determine whether the anti-inflammatory and cardioprotective properties of a novel adenosine A(2A) receptor agonist, ATL-146e (ATL), alone or in combination with the phosphodiesterase IV inhibitor rolipram would occur using very low, nonvasodilating doses. In a canine model of reperfused myocardial infarction, low-dose ATL given alone reduced infarct size by 45% (P < 0.05 vs. control). When ATL was combined with a very low dose of rolipram (0.001 microg.kg(-1).min(-1)), a marked reduction in P-selectin expression and neutrophil infiltration (51% lower; P < 0.001 vs. control) was seen and the infarct size reduction (58% lower; P < 0.01 vs. control) was greater than observed with ATL (45% lower; P < 0.05) or rolipram (33% lower; P < 0.05) alone. In conclusion, a low, nonvasodilating dose of ATL, a highly selective adenosine A(2A) receptor agonist, reduced infarct size after reperfusion. Furthermore, combining ATL and the phosphodiesterase IV inhibitor rolipram reduced infarct size even more than either agent alone. Such combination therapy may be beneficial clinically by potentiating cardioprotection after coronary reperfusion at doses far below those producing vasodilatation or side effects.

The potent A2A-selective adenosine receptor agonist WRC-0470 is a short-acting coronary vasodilator with potential utility for pharmacological stress perfusion imaging.

In the presence of stenoses that reduced or abolished regional flow reserve, (1) myocardial sestamibi uptake significantly underestimated the dobutamine-induced flow heterogeneity, (2) a "failure to increase systolic thickening" rather than a reduction in thickening was observed during dobutamine stress, and (3) myocardial stunning was observed during postdobutamine recovery.

Background-Adenosine (Ado) and dipyridamole are alternatives to exercise stress for myocardial perfusion imaging.Though generally safe, side effects frequently occur that cause patient discomfort and sometimes lead to premature termination of the study or require aminophylline administration. Recently, a new class of A 2A Ado receptor agonists was synthesized. ATL193 and ATL146e are 2-propynylcyclohexyl-5Ј-N-ethylcarboxamido derivatives of Ado. The study goals were to evaluate the potency and selectivity of these new compounds on recombinant canine Ado receptors and to evaluate their hemodynamic properties in dogs to assess their usefulness as vasodilators for myocardial perfusion imaging. Methods and Results-In assays of recombinant canine Ado receptors, ATL-193 and ATL-146e were highly selective for the A 2A over the A 1 and A 3 receptors and were more potent than MRE-0470 and CGS-21680. In 16 anesthetized dogs, the agonists were administered by infusion (ATL-193; nϭ7 normal) or bolus injection (ATL-146e; nϭ9 critical left anterior descending coronary artery stenosis), and hemodynamic responses were compared with those of Ado. Both agonists produced dose-dependent coronary flow (CF) elevation without provoking the hypotension observed with Ado.After an ATL-146e bolus, the CF increase was sustained for several minutes, providing ample time for injection and myocardial uptake of 99m Tc-sestamibi, and CF returned to baseline within 20 minutes. The CF increase was completely blocked by the selective A 2A antagonist ZM241385 (3 g · kg Ϫ1 · min Ϫ1 ). Conclusions-ATL-193 and ATL-146e are highly potent and selective Ado A 2A receptor agonists with excellent potential for use as vasodilators for myocardial perfusion imaging. An important advantage of ATL-146e is the ability to administer it by bolus injection.

In this canine model, relative underperfusion with adenosine stress is better resolved with 201Tl than with 99mTc-tetrofosmin and may be explained by the lower EF for 99mTc tetrofosmin. With clinical imaging, greater 201Tl attenuation and redistribution may lessen this advantage.