Effects of intravenous theophylline on exercise-induced myocardial ischemia. I. Impact on the ischemic threshold

Human Performance Laboratory, Memorial Hospital of Rhode Island, Pawtucket 02860.

OBJECTIVES. Theophylline has been shown to delay the onset of myocardial ischemia and to prolong exercise duration. The present study was done to evaluate the mechanisms and actions of intravenous theophylline on the onset of ischemia and exercise duration. BACKGROUND. The ischemic threshold may be altered by the differential coronary vasodilation induced by endogenous adenosine. Theophylline is a competitive receptor antagonist of adenosine and may have a potential as an anti-ischemic medication. METHODS. A double-blind, placebo-controlled crossover trial using an infusion of intravenous theophylline (8.0 +/- 2.0 mg/liter) or placebo before exercise in 12 patients was done. Oxygen uptake, heart rate, blood pressure and heart rate-blood pressure product were determined at the onset of > or = 0.1-mV ST segment depression and angina pectoris, as well as at peak exercise. The extent of myocardial ischemia was evaluated by electrocardiographic criteria and quantitation of thallium-201 images at peak exercise. RESULTS. When compared with placebo, theophylline significantly delayed time to the onset of exercise-induced ischemia. Ischemia occurred at a higher heart rate-blood pressure product and oxygen uptake. Exercise duration was prolonged but was not associated with greater ischemia, as determined by oxygen uptake, ST segment depression, angina pectoris and size of thallium-201 defect. CONCLUSIONS. It is concluded that theophylline favorably alters myocardial ischemia not only by delaying its onset but also by enabling it to occur at a higher threshold without causing deleterious effects during exercise. The mechanism for the increased ischemic threshold may be through the inhibition of adenosine and the coronary steal phenomenon.

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