Effects of adenosine on human coronary arterial circulation

Abstract

Adenosine is a potent vasodilator used extensively to study the coronary circulation of animals. Its use in humans, however, has been hampered by lack of knowledge about its effects on the human coronary circulation and by concern about its safety. We investigated in humans the effects of adenosine, administered by intracoronary bolus (2-16 μg), intracoronary infusion (10-240 μg/min), or intravenous infusion (35-140 μg/kg/min) on coronary and systemic hemodynamics and the electrocardiogram. Coronary blood flow velocity (CBFV) was measured with a 3F coronary Doppler catheter. The maximal CBFV was determined with intracoronary papaverine (4.5±0.2 · resting CBFV). In normal left coronary arteries (n=20), 16-μg boluses of adenosine caused coronary hyperemia similar to that caused by papaverine (4.6±0.7 · resting CBFV). In the right coronary artery (n=5), 12-μg boluses caused maximal hyperemia (4.4±1.0·resting CBFV). Intracoronary boluses caused a small, brief decrease in arterial pressure (similar to that caused by papaverine) and no changes in heart rate or in the electrocardiogram. The duration of hyperemia was much shorter after adenosine than after papaverine administration. Intracoronary infusions of 80 μg/min or more into the left coronary artery (n=6) also caused maximal hyperemia (4.4±0.1 · resting CBFV), and doses up to 240 μg/min caused a minimal decrease in arterial pressure (-6±2 mm Hg) and no significant change in heart rate or in electrocardiographic variables. Intravenous infusions in normal patients (R=25) at 140 μg/kg/min caused coronary vasodilation similar to that caused by papaverine in 84% of patients (4.4±0.9 · resting CBFV). At submaximal infusion rates, however, CBFV often fluctuated widely. During the 140-μg/kg/min infusion, arterial pressure decreased 6±7 mm Hg, and heart rate increased 24±14 beats/min. One patient developed 1 cycle of 2:1 atrioventricular block, but otherwise, the electrocardiogram did not change. In eight patients with microvascular vasodilator dysfunction (ACBFV, <3.5 peak/resting velocity after a maximally vasodilating dose of intracoronary papaverine), the dose-response characteristics to intracoronary boluses and intravenous infusions of adenosine were similar to those found in normal patients. These studies suggest that maximal coronary vasodilation can be achieved safely with intracoronary adenosine administration and that intravenous infusions at a rate of 140 μg/kg/min cause near-maximal coronary hyperemia in most patients.