Method
Intravenous adenosine: Continuous infusion and low dose bolus administration for determination of coronary vasodilator reserve in patients with and without coronary artery disease

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Abstract

To assess the use of adenosine as an alternative agent for determination of coronary vasodilator reserve, hemodynamics and coronary blood flow velocity were measured at rest and during peak hyperemic responses to continuous intravenous adenosine infusion (50, 100 and 150 μg/kg per min for 3 min) and intracoronary papaverine (10 mg) in 34 patients (17 without [group 1]and 17 with [group 2]significant left coronary artery disease), and in 17 patients (11 without and 6 with left coronary artery disease) after low dose (2.5 mg) intravenous bolus injection of adenosine.

The maximal adenosine dose did not change mean arterial pressure (−10 ± 14% and −6 ± 12% for groups 1 and 2, respectively) but increased the heart rate (15 ± 18% and 13 ±16%, respectively). For continuous adenosine infusions, mean coronary flow velocity increased 64 ± 104%, 122 ± 94% and 198 ± 59% and 15 ± 51%, 110 ± 95% and 109 ± 86% in groups 1 and 2, respectively for each of the three doses. Mean coronary flow velocity increased significantly after 100 and 150 μg/kg of adenosine and 10 mg of intracoronary papaverine (48 ± 25, 52 ±19 and 54 ± 21 cm/s, respectively; all p < 0.05 vs. baseline) and was significantly higher than in group 2 (37 ± 24, 32 ± 16, 41 ± 23 cm/s; all p < 0.05 vs. group 1). The coronary vasodilator reserve ratio (calculated as the ratio of hyperemic to basal mean flow velocity) for adenosine and papaverine was 2.94 ± 1.50 and 2.94 ± 1.00, respectively, in group 1 and was significantly and similarly reduced in group 2 (2.16 ± 0.81 and 2.38 ± 0.78, respectively; both p < 0.05 vs. group 1). Low dose bolus injection of adenosine increased mean velocity equivalenty to that after continuous infusion of 100 μg/kg, but less than after papaverine. There was a strong correlation between adenosine infusion and papaverine for both mean coronary flow velocity and coronary vasodilator reserve ratio (r2= 0.871 and 0.325; SEE = 0.068 and 0.189, respectively; both p < 0.0005).

No patient had significant arrhythmias or prolongation of the corrected QT (QTc) interval with adenosine, but papaverine increased the QTc interval from 445 ± 44 to 501 ± 43 ms (p < 0.001 vs. both maximal adenosine and baseline) and produced nonsustained ventricular tachycardia in one patient.

These data indicate that intravenous adenosine in doses >100 μg/kg (and in low dose bolus injections) for most patients is nearly equivalent to intracoronary papaverine without producing QTc prolongation, making this agent a potentially superior and safer alternative to intracoronary papaverine for determination of coronary vasodilator reserve.

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This study was presented in part at the 63rd Scientific Session of the American Heart Association, Dallas, Texas, November 1990. The study drug was provided by AB Hassle, Inc., Göteborg, Sweden.