RESPIRATORY CONSEQUENCES OF OPIATES

阿片类药物的呼吸系统后果

• 批准号: 3337230
• 负责人: TEODORO V SANTIAGO
• 金额: $ 18.99万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-01-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3337230
• 关键词: carboxyhemoglobin; cats; dogs; drug adverse effect; drug interactions; dyspneas; electromyography; emphysema; goats; human subject; hypercapnia; laboratory rabbit; naloxone; neural information processing; neurochemistry; neuropeptide receptor; neuropeptides; opiate alkaloid; pulmonary respiration; radiotracer; respiratory airway volume; respiratory muscles; respiratory pharmacology; sleep

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.

在成年动物和人类受试者中，内源性阿片类药物调节 在气道阻力增加的条件下进行通风。 这种调制的表现包括潮汐抑郁 急性流动性期间的体积和二氧化碳化学敏度 在山羊中加载，以及在 一些慢性气流阻塞的患者。 我们有 建议在这种情况下的阿片类药物阐述可缓解呼吸困难 并可能推迟呼吸肌肉的疲劳。 在 拟议的研究，阿片类药物和阿片类药物的机制 在呼吸道增加的情况下调节呼吸 电阻将进一步探索。 第一个特定假设 是选择性抑制负荷补偿的一个方面 （招募呼气肌肉）通过阿片类药物诱导 药物并通过激活内源性阿片类药物系统。 检验吗啡对单独的作用的实验 正常受试者的负载补偿方面将是 执行。 在单独的实验中，纳洛酮对 将检查未负载补偿COPD患者 确定在这些方面丢失了哪个方面 患者并通过纳洛酮恢复。 负载方面 将系统分析的补偿是（1）增加 在灵感肌肉的活动中； （2）招募 呼气肌肉； （3）灵感持续时间的延长。 几种灵感和呼气的肌肉将同时 受监控。 我们将研究急性和 持续的流动载荷对电活动的电活动 不同的呼吸道肌肉将同时测量 隔膜在体内的长度通过体学计量学。 第二个 特定的假设是脚震和呼吸困难激活 内源性阿片类药物以类似的方式导致 大脑中β-内啡肽的相似分布。 每个刺激 将给予单个动物和浓度变化 将在已知的大脑结构中检查β-内啡肽的 包含阿片类药物。 拟议的研究应散发出更多的光线 关于Opiods和呼吸之间的相互作用。 他们也携带 控制患者呼吸的临床意义 慢性阻塞气流和防止衰减不足 面对气道阻塞的增加。