BackgroundPharmacological stress imaging with adenosine or dipyridamole is associated with a high incidence of side effects, including hypotension, chest pain, AV conduction abnormalities, and bronchospasm. Although the desired coronary vasodilatory response is mediated primarily by the adenosine A_2Areceptors, these side effects result from stimulation of the A₁, A_2B, or A₃adenosine receptors. We hypothesized that a selective adenosine A_2Areceptor agonist would induce coronary vasodilatation appropriate for pharmacological stress imaging, without evoking adenosine receptor–mediated side effects.Methods and ResultsInfusions of a potent and selective A_2Aadenosine receptor agonist, WRC-0470 (0.1 to 3 μg · kg⁻¹·min⁻¹for 10 minutes), to five open-chest dogs produced dose-related left anterior descending (LAD) and left circumflex (LCx) coronary artery vasodilatation without altering mean arterial pressure, heart rate, left atrial pressure, or left ventricular dP/dt. In the same dogs, adenosine (300 μg · kg⁻¹· min⁻¹for 4 minutes) produced coronary vasodilatation that was limited by significant hypotension. To determine the utility of WRC-0470 for pharmacological stress imaging, the hemodynamic responses to WRC-0470 (0.6 μg · kg⁻¹· min⁻¹for 10 minutes) and adenosine (250 μg · kg⁻¹· min⁻¹for 4 minutes) were compared in dogs with critical LAD stenoses.²⁰¹Tl was injected at the peak WRC-0470 stress response. WRC-0470 increased LCx flow nearly fivefold but did not significantly lower mean arterial pressure. Anteroseptal defects were readily apparent in slice images from all dogs. The mean defect ratio (LAD/LCx) was 0.59±0.06.ConclusionsThe potent A_2A-selective adenosine receptor agonist WRC-0470 is a short-acting coronary vasodilator with potential utility for pharmacological stress perfusion imaging.

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