Effects of intravenous theophylline on exercise-induced myocardial ischemia: II. A concentration-dependent phenomenon

Objectives. The effects of varying concentrations of theophylline on exercise-induced myocardial ischemia were evaluated in patients with stable coronary artery disease. Background. Theophylline is a competitive antagonist of adenosine and may have potential as an anti-ischemic medication. It is not known whether these effects on myocardial ischemia are concentration dependent. Methods. In a double-blind, randomized, crossover manner, 11 patients received, at 1-week intervals, placebo and each of three theophylline doses by intravenous infusion for 45 min. Graded exercise testing was performed before randomization and immediately after each infusion. Concurrent anti-ischemic medications were withheld for 24 h before each exercise test. Serum theophylline concentrations achieved were 3.9 ± 1.0 mg/liter (low), 8.2 ± 1.8 mg/liter (medium) and 13.2 ± 2.3 mg/liter (high). Results. Compared with placebo, none of the three theophylline infusions produced a significant alteration in rest heart rate, blood pressure, mean frequency or severity of ventricular ectopic activity or noncardiac symptoms. The time to onset of ischemia was progressively increased, with medium and high concentrations achieving statistical significance. Similar patterns were observed for oxygen uptake and the heart rate-systolic blood pressure product at the onset of ischemia. Total exercise duration was significantly prolonged with the medium and high concentrations. Conclusions. It is concluded that administration of varying doses of theophylline before exercise produces a clinically significant and concentration-dependent improvement in the indicators of myocardial ischemia in patients with chronic stable coronary artery disease.