RESPIRATORY CONSEQUENCES OF OPIATES

在成年动物和人类受试者中，内源性阿片样物质调节 在气道阻力增加的情况下进行通气。 这种调制的表现包括潮汐的降低， 急性血流阻力期间的容量和CO2化学敏感性 山羊的负载，以及 一些慢性气流阻塞的患者。 我们有 表明阿片类药物在这种情况下的作用缓解了呼吸困难 并可能延缓呼吸肌的疲劳。 在 建议的研究，阿片类药物和阿片类药物 在气道增加的情况下调节呼吸 将进一步探讨阻力问题。 第一个具体假设 选择性地抑制负载补偿一个方面 （呼气肌的募集）是由阿片类药物引起的 药物和通过激活内源性阿片系统。 研究吗啡对分离的 正常受试者的负荷补偿方面将是 执行。 在单独的实验中，纳洛酮对 将对无负荷补偿的COPD患者进行检查， 确定负载补偿的哪些方面在这些 纳洛酮可使其恢复。 负载方面 将系统分析的补偿是（1）增加 （2）吸气肌的活动;（3） （3）延长吸气时间。 几个吸气和呼气肌肉将同时 监测。 我们将研究急性和慢性炎症的影响， 持续的流阻负荷对电活动的 不同的呼吸肌，同时测量 通过声测显微术测量体内隔膜的长度。 第二 具体假设是，足电击和呼吸困难应激激活了 内源性阿片系统以类似的方式，并会导致 大脑中β-内啡肽的分布相似。 每个刺激 将给予个体动物， 将在已知的大脑结构中检查β-内啡肽， 含有阿片类药物 拟议中的研究应能提供更多信息， 阿片类药物和呼吸之间的相互作用。 他们还携带 控制呼吸的临床意义 慢性气流阻塞和防止换气不足 面对日益严重的气道阻塞

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.