Role of Endogenous Adenosine in Hypoxic Ventilatory Depression

点击翻译按钮获取中文摘要

Study (I)We studied the effect of theophylline, an adenosine receptor antagonist, on the tissue oxygenation and acid-base status in the brain in healthy volunteers (n=6). Partial gas pressures and oxygen saturation (SO2) in an artery and the internal jugular vein were simultaneously measured during normoxia and isocapnic hypoxia (PaO2=60, 45 mmHg) before and after infusion of theophylline. PjO2 as well as SjO2 markedly dropped after theophylline infusion. On the other hand, PjCO2 and pHj did not change in the two studies despite slightly but significantly low PaCO2 and high pHa with theophylline. Based on the assumption that parameters of jugular venous blood reflect those of the brain tissue, these data provide insight into the mechanism of ventilation-stimulating effect of theophylline and suggest a possible adverse effect of theophylline on the brain.Study (II)To examine a role of endogenous adenosine in hypoxic ventilatory response, we measured, in nine normal adults, ventilatory r … More esponses to isocapnic progressive and subsequent sustained hypoxia with and without pretreatment with dipyridamole, an adenosine uptake blocker, which increases plasma levels of adenosine. Pretreatment with dipyridamole significantly augmented the slope of the ventilatory response to isocapnic progressive hypoxia, suggesting a possible role of endogenous adenosine for the activity of peripheral chemoreceptors. During 20 min of sustained hypoxia, ventilation gradually declined to intermediate levels in both studies. However, the decline in ventilation began earlier and was more marked with dipyridamole. When theophylline alone, adenosine receptor antagonist, was injected in 4 out of 9 subjects, the ventilatory decline seen during sustained hypoxia was attenuated. In addition, dipyridamole following theophylline infusion no longer produced any significant change on ventilatory response to sustained hypoxia compared to theophylline alone. We therefore conclude that endogenous adenosine may play a modulatory role both peripherally and centrally in hypoxic ventilatory response in humans. Less