Effect of theophylline on brain tissue oxygenation during normoxia and hypoxia in humans

Although theophylline, an adenosine receptor antagonist, is known to reduce cerebral blood flow, little clinical attention has been paid to this adverse effect. This study was designed to examine the effect of theophylline on brain tissue oxygenation for a wide range of arterial PO2 in healthy volunteers. Partial gas pressures and O2 saturation in an artery (SaO2) and the internal jugular vein (SjO2) were simultaneously measured while subjects (n = 6) were breathing room air and then exposed to two levels of isocapnic hypoxia (arterial PO2 = 60 and 45 Torr) before and after infusion of theophylline (6 mg/kg of aminophylline). For the same levels of arterial oxygenation, jugular vein PO2 markedly dropped, by 3-5 Torr, after theophylline infusion, as did SjO2, by as much as 6-10%, under the arterial PCO2, which was slightly lower by 1-2 Torr in the theophylline study. By use of the linear regression lines obtained from the relationship between SaO2 and SjO2 in each study, it was calculated that the SjO2 with theophylline, while SaO2 was 95, 90, and 80%, was comparable to that without theophylline when SaO2 was 81, 78, and 73%, respectively. On the basis of the assumption that partial gas pressures and SjO2 reflect brain tissue oxygenation, these data suggest that the effect of theophylline on brain tissue oxygenation should not be ignored in some clinical settings. The effects of chronic administration remain to be studied.