Effect of N-0861, a selective adenosine A1 receptor antagonist, on pharmacologic stress imaging with adenosine

N6-endonorboman-2-yl-9-methyladenine (N-0861) is a drug which inhibits the A1 adenosine receptor subtype. One proposed use for N-0861 is to eliminate A1 receptor-mediated side effects such as A-V heart block and possibly angina in patients undergoing pharmacologic stress with adenosine. The goal of this study was to determine whether N-0861 has any crossover effect on the A2 vasodilatory action of adenosine or on 201TI uptake which would adversely affect imaging of coronary stenoses.

In eight dogs with critical left anterior descending (LAD) stenoses, we compared the hemodynamic response to intravenous adenosine (250 micrograms/kg/min) before and after N-0861 administration. LAD and left circumflex (LCx) coronary flows were measured ultrasonically and regional blood flow was assessed using microspheres. Thallium-201 (18.5-37.0 MBq) was injected during adenosine hyperemia while N-0861 was present. Imaging of heart slices was performed and defect magnitude was calculated as LAD:LCx count ratios from regions of interest (ROIs) on images. Regional 201Tl activity and microsphere flow were determined by gamma well counting.

There was no change in mean heart rate, arterial and left atrial pressures, +dP/dt, and ultrasonically measured LAD and LCx coronary flows upon N-0861 administration. In addition, adenosine evoked a similar hemodynamic response after N-0861. There was also no change in coronary flow in the critically stenotic LAD but LCx flow tripled to 106 +/- 14 ml/min (p < 0.01).

These data indicate that N-0861 pretreatment does not adversely affect adenosine A2 receptor-mediated vasodilation and has no effect on the detection of a critical coronary stenosis by 201Tl imaging. Thus, the pretreatment strategy may prove useful for the elimination of A1 receptor-mediated side effects during pharmacologic stress imaging with adenosine.