Contrasting effects of two xanthines, theophylline and enprofylline, on the cardio‐respiratory stimulation of infused adenosine in man

Six normal male subjects, ages 28–40 years, were studied on separate days during increasing infusions with adenosine, 40–120 μ g kg ‐1 min ‐1 , before and during infusions of two xanthine derivatives, theophylline (mean plasma concentration 9 mg 1 –1 ) and enprofylline (mean plasma concentration 3 mg 1 –1 ). The study was double‐blind, randomized, placebo controlled. Cardio‐respiratory variables were measured non‐invasively. Adenosine by itself increased heart rate ( P < 0.05), skin temperature ( P < 0.05), resting minute ventilation ( P < 0.01) and decreased estimated P a, CO2 ( P < 0.01). Compared with placebo enprofylline increased heart rate ( P < 0.05) and shifted the heart rate and ventilation dose–response curves of adenosine upwards ( P < 0.05 and P < 0.02, respectively). Theophylline did not by itself affect heart rate but significantly ( P < 0.05) reduced the heart rate response to adenosine. Compared with placebo theophylline caused a small increase in minute ventilation ( P < 0.05) and flattened the dose‐response curves of the effects of adenosine on ventilation ( P < 0.01) and P a, CO2 , ( P < 0.01). Theophylline also reduced abdominal and chest discomfort caused by adenosine permitting significantly ( P < 0.05) higher infusion rates of adenosine. These findings suggest that, with equipotent bronchodilating plasma concentrations, theophylline can inhibit while enprofylline augments some cardio‐respiratory stimulant effects of infused adenosine in man.