The intravenous infusion of adenosine provokes anginalike chest pain. To establish its origin, an intracoronary infusion of increasing adenosine concentrations was given in 22 patients with stable angina pectoris. During adenosine infusion, 20 patients had chest pain without electrocardiographic signs of ischemia. They all reported that the chest pain was similar to their usual anginal pain. In 10 of the 22 patients adenosine was also infused into the right atrium, but it never produced symptoms at the doses that had provoked chest pain during intracoronary infusion. In seven other patients, the intracoronary adenosine infusion was repeated after intravenous administration of aminophylline, an antagonist of adenosine P1-receptors. Aminophylline decreased the severity of adenosine-induced chest pain (assessed with a visual analog scale) from 42±22 to 23±17 mm (p<0.002). In the remaining five of the 22 patients, monitoring of blood oxygen saturation in the coronary sinus during intracoronary adenosine administration showed that maximum coronary vasodilation was achieved at doses lower than those responsible for chest pain. A single-blind, placebo-controlled, randomized trial of the effect of aminophylline on exercise-induced chest pain was also performed in 20 other patients with stable angina. Aminophylline, compared with placebo, decreased the severity of chest pain at peak exercise from 67±21 to 51±23 mm (p<0.02), despite the achievement of a similar degree of ST-segment depression. Finally, the effect of intravenous adenosine was compared in 10 patients with predominantly painful myocardial ischemia and in 10 patients with predominantly silent ischemia. The latter tolerated a longer period of adenosine infusion and developed significantly less severe chest pain than patients with painful ischemia (18±3.6 vs. 14.4±3.6 minutes, p<0.05 and 26±28 vs. 63±23 mm, p<0.02, respectively). Thus, intracoronary adenosine administration provokes chest pain similar to the anginal pain at doses that do not produce symptoms during intra-atrial infusion. Furthermore, aminophylline, an adenosine P1-receptor antagonist, significantly reduces the severity of both adenosine and exercise-induced chest pain. These findings indicate that adenosine is a stimulus adequate to produce cardiac pain and could be partially responsible for the anginal pain during myocardial ischemia. This effect does not seem to be related to adenosine-induced coronary dilation and appears predominantly mediated by P1-receptor stimulation. The fact that the severity of chest pain provoked by intravenous adenosine is less in patients with silent ischemia, although difficult to interpret because of the systemic algogenic effects of this substance, further supports the hypothesis that adenosine may play an important role in the production of the anginal pain.
