RESPIRATORY CONSEQUENCES OF OPIATES

在过去的几年里，人们已经认识到，身体产生 在特定生理和病理条件下具有阿片活性的物质 情况。这引起了人们对吸入的相当大的兴趣。 阿片类药物的强效呼吸抑制作用。这个 拟议的研究将继续检查这些内源性因素的作用。 在呼吸和气体交换过程中产生的阿片类物质(即内啡肽)。 利用β-内啡肽活性的直接测定和通过 阿片受体拮抗剂纳洛酮对内啡肽的影响 呼吸，三个一般区域选择的基础上，内啡肽是 已知的被释放或使人联想到吗啡的影响将被表现出来 被研究。在正常人类志愿者中，非应激诱导的影响 (甲替拉酮)内啡肽对通气性和控制性的阐述 将对清醒和睡眠时的呼吸进行评估。假说 这些内啡肽会改变和抑制呼吸并产生 将测试与睡眠有关的呼吸不规律。在患有 慢性阻塞性肺疾病(COPD)--内啡肽的假说 精细是运动缓解呼吸困难的机制 将对康复进行检查。最后，在呼吸道动物模型中 梗阻与肺损伤、内啡肽释放及其对肺功能的影响 将研究呼吸和气体交换；假设 内源性鸦片类药物有助于疲劳的产生， 减少急性肺损伤分流样低氧的程度 帮助产生呼吸适应(即，负荷受损 对慢性呼吸道阻塞的代偿)应予以阐明。这个 拟议的研究直接关系到对几个临床问题的理解 问题包括肺气肿、睡眠呼吸暂停和成人呼吸 窘迫综合症。确定内啡肽在这些条件下的影响 应该会提高我们预测这些呼吸反应的能力 病人。

Over the last several years, it has been recognized that the body generates substances with opioid activity under specific physiologic and pathologic situations. This has elicited considerable interest regarding breathing in view of the potent respiratory depressant effects of opiate drugs. The proposed studies will continue to examine the role of these endogenously generated opiates (i.e., endorphins) on respiration and gas exchange. Utilizing both direct assays of beta-endorphin activity and reversal by the opiate antagonist naloxone of the postulated endorphin effects on breathing, three general areas selected on the basis that endorphins are known to be released or effects reminiscent of morphine are manifested will be studied. In normal human volunteers, the effects of non-stress-induced (Metyrapone) endorphin elaboration on ventilation and the control of breathing during wakefulness and sleep will be evaluated. The hypothesis that these endorphins will modify and depress breathing and generate sleep-related irregularities of breathing will be tested. In patients with Chronic Obstructive Pulmonary Disease (COPD), the hypothesis that endorphin elaboration is the mechanism for the relief of dyspnea by exercise rehabilitation will be examined. Finally, in animal models of airway obstruction and lung injury, endorphin release and their effects on respiration and gas exchange will be investigated; the hypothesis that endogenously generated opiates contribute to the generation of fatigue, minimize the magnitude of the shunt-like hypoxia of acute lung injury and help generate the ventilatory adaptations (i.e., impaired load compensation) to chronic airway obstruction should be elucidated. The proposed studies directly bear on the understanding of several clinical problems including emphysema, sleep apnea and the Adult Respiratory Distress Syndrome. Identifying endorphin influences in these conditions should improve our ability to predict the ventilatory responses of these patients.