Role of Endogenous Adenosine in Hypoxic Ventilatory Depression

研究（一）我们研究了腺苷受体拮抗剂茶碱对健康志愿者（n=6）脑组织氧合和酸碱状态的影响。在正常氧和等二氧化碳缺氧（PaO2=60，45 mmHg）时，在动脉和颈内静脉中的气体分压和氧饱和度（SO2），同时测量之前和之后输注茶碱。茶碱滴注后PjO2和SjO2均明显下降。另一方面，在两项研究中，PjCO2和pHj没有变化，尽管茶碱轻微但显著地降低了PaCO2和升高了pHa。根据颈静脉血参数反映脑组织参数的假设，这些数据提供了对茶碱通气刺激作用机制的深入了解，并提示茶碱对脑的可能的不利影响。研究（II）为了检测内源性腺苷在缺氧性呼吸反应中的作用，我们测定了9名正常成人的呼吸反应，其中1名为正常对照组，另1名为正常对照组。 ...更多信息 对等二氧化碳进行性和随后的持续缺氧有反应，有或没有用双嘧达莫预处理，双嘧达莫是一种腺苷摄取阻断剂，可增加腺苷的血浆水平。潘生丁预处理显着增加了斜率的等二氧化碳渐进性缺氧的缓解反应，提示内源性腺苷外周化学感受器的活性的可能作用。在20分钟的持续缺氧，通气逐渐下降到中间水平，在两项研究。然而，通气功能的下降开始较早，并且在潘生丁组更为明显。当单独注射腺苷受体拮抗剂茶碱时，9名受试者中的4名在持续缺氧期间观察到的呼吸下降减弱。此外，与单独茶碱相比，茶碱输注后的双嘧达莫不再对持续缺氧的缓解反应产生任何显著变化。因此，我们得出结论，内源性腺苷可能发挥调节作用的外周和中枢在人体缺氧性反应。少

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