EFFECTS OF INTRAVENOUS THEOPHYLLINE ON EXERCISE-INDUCED MYOCARDIAL-ISCHEMIA .2. A CONCENTRATION-DEPENDENT PHENOMENON

Objectives. The effects of varying concentrations of theophylline on e xercise-induced myocardial ischemia were evaluated in patients with st able coronary artery disease. Background. Theophylline is a competitiv e antagonist of adenosine and may have potential as an anti-ischemic m edication. It is not known whether these effects on myocardial ischemi a 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 mi n. Graded exercise testing was performed before randomization and imme diately after each infusion. Concurrent anti-ischemic medications were withheld for 24 h before each exercise test. Serum theophylline conce ntrations achieved were 3.9 +/- 1.0 mg/liter (low), 8.2 +/- 1.8 mg/lit er (medium) and 13.2 +/- 2.3 mg/liter (high). Results. Compared with p lacebo, none of the three theophylline infusions produced a significan t alteration in rest heart rate, blood pressure, mean frequency or sev erity of ventricular ectopic activity or noncardiac symptoms. The time to onset of ischemia was progressively increased, with medium and hig h concentrations achieving statistical significance. Similar patterns were observed for oxygen uptake and the heart rate-systolic blood pres sure product at the onset of ischemia. Total exercise duration was sig nificantly prolonged with the medium and high concentrations. Conclusi ons. It is concluded that administration of varying doses of theophyll ine before exercise produces a clinically significant and concentratio n-dependent improvement in the indicators of myocardial ischemia in pa tients with chronic stable coronary artery disease.