Effect of Theophylline on Brain Acid-Base Status during Normoxia and Hypoxia in Humans

Abstract

Theophylline, a methylxanthine, is known to stimulate ventilation and augment the ventilatory response to hypoxia in humans by several proposed mechanisms.^{1, 2} Since theophylline, an adenosine receptor antagonist, has been shown to substantially reduce cerebral blood flow (CBF) in humans,^{3, 4} as well as in some animal species,⁵ these effects may have some relevance to the ventilation-stimulating effect of theophylline. If the acid-base status in the brain is altered as a consequence of changes in CBF, it would affect the activity of the central chemosensitivity and thus the level of ventilation. Since some animal studies have shown that effects of theophylline on CBF are apparent during hypoxia but not during normoxia,^{6, 7} the effect of theophylline on the PCO₂ and acid-base status in the brain may be changeable during normoxia and hypoxia. One approach by which we can approximately estimate what is occurring in the brain in humans is to measure partial gas pressures and pH in the internal jugular vein. With a technique for sampling blood from the internal jugular vein, we have previously shown that PCO₂ in the internal jugular vein significantly decreases, by 2 to 3 mmHg, under isocapnic hypoxia,^{8, 9} which probably reflects hypoxia-induced cerebral vasodilation. The aims of this study are first to evaluate the effect of theophylline on PCO₂ and pH in the internal jugular vein for a wide range of arterial PO₂ (PaO₂) under isocapnic conditions and second to examine the possibility that the augmented ventilatory response to hypoxia caused by theophylline is due to attenuation of hypoxia-induced cerebral vasodilation.