Intracoronary and intravenous adenosine 5′-triphosphate, adenosine, papaverine, and contrast medium to assess fractional flow reserve in humans

Background - Inducing both maximal and steady-state coronary hyperemia is of clinical importance to take full advantage of fractional flow reserve measurements. The present study compares different dosages and routes of administration of adenosine 5′-triphosphate (ATP), adenosine, contrast medium, and papaverine regarding their potential to achieve both maximal and steady-state hyperemia. Methods and Results - In 21 patients with an isolated coronary stenosis, coronary vasodilation was induced successively by papaverine (20 mg intracoronary), adenosine (20 and 40 μg intracoronary), ATP (20 and 40 μg intracoronary), iohexol (6 mL intracoronary), adenosine or ATP through an antecubital vein (140 and 180 μg · kg^-1 · min-¹), or adenosine or ATP through a femoral vein (140 and 180 μg · kg^-1 · min^-1). Because vessel dimensions did not change, the ratio of distal coronary pressure (Pd) to aortic pressure (P_d) was used as an index of myocardial resistance. P_d/P_a was 0.77±0.21 at rest and decreased to 0.61±0.21 after papaverine. P_d/P_a decreased to a similar level with all other vasodilators, except with contrast medium (0.68±0.21; P<0.01 versus papaverine). Steady-state hyperemia could only be obtained by intracoronary papaverine and by intravenous ATP or adenosine. In another 23 patients, an intravenous infusion of ATP was varied from 0 to 280 μg · kg^-1 · min^-1. At doses >140 μg · kg^-1 · min^-1, there was neither a further decrease in P_d/P_a ratio nor a further increase in coronary flow velocities. Conclusion - Provided sufficient dosages are used, ATP, adenosine, and papaverine (but not contrast medium) induce maximal hyperemia and are therefore suitable to assess fractional flow reserve. Only intracoronary papaverine and intravenous ATP or adenosine induce steady-state hyperemia enabling a pressure pullback maneuver that is useful in assessing diffuse coronary atherosclerosis.