RESPIRATORY CONSEQUENCES OF OPIATES

在成年动物和人类受试者中，内源性阿片类药物调节 在呼吸道阻力增加的情况下进行通风。 这种调制的表现包括潮汐抑制。 急性流阻期间的容量和二氧化碳化学敏感性 山羊的负载和流阻负载补偿的损失 一些有慢性气流阻塞的患者。我们有 提示在这种情况下阿片类药物的精加工可以缓解呼吸困难 并可能延缓呼吸肌的疲劳。在 拟议的研究，阿片剂和阿片类药物的作用机制 在呼吸道增加的情况下调节呼吸 将进一步探讨抗药性。第一个具体假设 是对负载补偿一个方面的选择性抑制 (呼气肌的募集)是由阿片类药物引起的 药物和内源性阿片系统的激活。 吗啡对分离能力影响的实验研究 正常受试者的负荷补偿方面将是 已执行。在单独的实验中，纳洛酮对 非负荷代偿型COPD患者将接受检查以 确定负荷补偿的哪个方面(S)在这些方面丢失 患者，用纳洛酮恢复。负荷的各方面 将系统分析的薪酬是：(1)增加 在吸气肌的活动；(2)招募 呼气肌；(3)吸气时程延长。 几块吸气肌和呼气肌将同时 被监视着。我们将调查急性和非传染性疾病的影响 持续的流阻负载对电活性的影响 不同的呼吸肌并将同时测量 通过声学显微镜测量活体横隔膜的长度。第二 具体的假设是足底电击和呼吸困难应激激活 内源性阿片系统以类似的方式发生，并将导致 类似的β-内啡肽在大脑中的分布。每种刺激 将被给予个体动物和浓度的变化 将在已知的大脑结构中检查β-内啡肽 含有阿片类药物。拟议中的研究应该会带来更多的启示 阿片类药物与呼吸之间的相互作用。他们还携带 慢性阻塞性肺疾病患者呼吸控制的临床意义 慢性气流阻塞和防止换气不足 面对日益严重的呼吸道阻塞。

In adult animals and human subjects, endogenous opioids modulate ventilation under conditions of increased airway resistance. Manifestations of this modulation include depression of tidal volume and CO2 chemosensitivity during acute flow-resistive loading in goats, and loss of flow-resistive load compensation in some patients with chronic airflow obstruction. We have suggested that opioid elaboration in this setting relieves dyspnea and possibly postpones fatigue of the respiratory muscles. In the proposed studies, the mechanisms by which opiates and opioids modulate breathing during conditions of increased airway resistance will be further explored. The first specific hypothesis is that selective inhibition of one aspect of load compensation (recruitment of expiratory muscles) is induced both by opiate drugs and by activation of the endogenous opioid system. Experiments examining the effect of morphine on separate aspects of load compensation in normal subjects will be performed. In separate experiments, the effects of naloxone on non-load compensating COPD patients will be examined to determine which aspect(s) of load compensation is lost in these patients and which is restored by naloxone. Aspects of load compensation that will be systematically analyzed are (1) increase in activity of the inspiratory muscles; (2) recruitment of expiratory muscles; and (3) prolongation of inspiratory duration. Several inspiratory and expiratory muscles will be simultaneously monitored. We will investigate the effects of both acute and sustained flow-resistive loading on electrical activity of the different respiratory muscles and will simultaneously measure length of the diaphragm in vivo by sonomicrometry. The second specific hypothesis is that footshock and dyspneic stress activate the endogenous opioid system in a similar manner and will cause a similar distribution of beta-endorphins in the brain. Each stimuli will be given to individual animals and changes in concentrations of beta-endorphins will be examined in brain structures known to contain the opioid. The proposed studies should shed more light on the interaction between opiods and breathing. They also carry clinical implications for the control of breathing in patients with chronic obstruction to airflow and for preventing hypoventilation in the face of increasing airway obstruction.