ANESTHESIA AND AIRWAYS

这项研究计划的长期目标是继续阐明 全身过程中肺气体交换受损的潜在机制 麻醉。这个项目的具体目标是检验这一假设 麻醉剂引起的直立性肺阻力 机械装置。肺阻力不仅由压力决定 沿呼吸道损失(呼吸道阻力)，但在很大程度上也是由 肺组织压力-体积滞后引起的压力损失 (组织阻力)。我们建议检验麻醉剂的假说 改变人体的呼吸道阻力和组织阻力(特定目标 1)。组织抵抗力可以通过麻醉剂的作用而改变 表面活性物质的功能，呼吸道的平滑肌肉或 肺泡管或这些影响的组合。如果麻醉剂有一种 对肺泡管平滑肌的影响，可能与肺气体交换有关 受影响，因为肺泡管中的平滑肌肉可能会 肺泡间隔紧张。如果麻醉剂能够松弛这些纤维，以前 紧张的肺泡间隔可能会松弛，从而降低表面积与体积之比。 在肺中的比率。在具体目标1中，我们还将确定N20是否已 对呼吸道阻力的影响。在具体目标2中，我们将研究 挥发性麻醉剂抑制呼吸道平滑肌的假说 通过减少支配肌肉的神经的活动来收缩，通过 对平滑肌细胞的直接作用和对呼吸道的影响 上皮性功能。这一目标解决了两个以前没有得到重视但 重要的几点。首先，区分神经调节和神经调节 麻醉剂对呼吸道的直接影响很重要，因为在体内 反射性刺激和直接刺激均可引起气道平滑肌收缩。 例如，气管插管引起的喉部刺激可能 主要是通过反射机制来收缩呼吸道。相反， 免疫刺激或在免疫刺激过程中释放的体液介质 哮喘可能直接影响呼吸道平滑肌细胞。其次，如果 麻醉药影响上皮功能，然后患者的反应 对挥发性麻醉剂损伤的呼吸道上皮(如哮喘患者)可能 被改变。在第三个具体目标中，我们将检验假设 注射麻醉剂对大鼠低碳酸血症时支气管收缩的影响 狗。低碳酸性支气管收缩的减弱可能会导致 对区域P(CO2)差异的呼吸道反应丧失。这可能会导致 麻醉期间VA/Q错配增加。我们希望检验我们的假设 注射麻醉剂对低碳酸血症的干扰可能较小 比挥发性麻醉剂更能抑制支气管收缩。

The long-term goal of this research program is to continue to elucidate the underlying mechanism for impaired pulmonary gas exchange during general anesthesia. The specific goal of this project is to test the hypothesis that anesthetic agents a ' erect pulmonary resistance by a number of mechanisms. Pulmonary resistance is not only determined by the pressure loss along the airways (airway resistance), but also to a large extent by the pressure loss caused by the pressure-volume hysteresis of lung tissue (tissue resistance). We propose to test the hypothesis that anesthetics alter in humans both airway resistance and tissue resistance (specific aim 1). The tissue resistance could be altered by an effect of anesthetics on the function of the surfactant, the smooth muscles of the airways or alveolar ducts or a combination of these effects. If anesthetics had an effect on alveolar duct smooth muscles, pulmonary gas exchange may be affected, because the smooth muscles in the alveolar ducts may keep alveolar septa tense. If anesthetics were to relax these fibers, previously tense alveolar septa may slacken, thus decreasing the surface to volume ratio in the lung. In specific aim 1 we will also determine whether N20 has an effect on airway resistance. In specific aim 2 we will examine the hypothesis that volatile anesthetics inhibit airway smooth muscle constriction by reducing activity in nerves innervating the muscle, by direct effects on the smooth muscle cell, and by effects on airway epithelial function. This aim addresses two previously unappreciated but important points. First, distinguishing between neurally-mediated and direct effects of anesthetics on the airways is important because in vivo airway smooth muscle may be constricted by both reflex and direct stimuli. For example, laryngeal irritation caused by an endotracheal tube may constrict the airways predominantly by a reflex mechanism. Conversely, humoral mediators released in response to an immunologic stimulus or during asthma may directly affect the airway smooth muscle cell. Secondly, if anesthetics affect epithelial function, then the response of patients with damaged airway epithelium (such as asthmatics) to volatile anesthetics may be altered. In the third specific aim we will test the hypothesis that injectable anesthetic agents attenuate hypocapnic bronchoconstriction in dogs. Attenuation of the hypocapnic bronchoconstriction may result in a loss of airway response to differences in regional P(CO2). This may cause increased VA/Q mismatch during anesthesia. We wish to test our hypothesis that injectable anesthetics may interfere less with hypocapnic bronchoconstriction than volatile anesthetics.