AUTONOMIC AND VASCULAR EFFECTS OF DESFLURANE IN HUMAN

地氟烷对人体自主神经和血管的影响

• 批准号: 2187502
• 负责人: Thomas Jay Ebert
• 金额: $ 12.08万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-15 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2187502
• 关键词: aging; analog; anesthetics; autonomic nervous system; baroreceptors; baroreflex; blood circulation; blood pressure; cardiovascular function; drug adverse effect; drug screening /evaluation; fentanyl; heart rate; human subject; isoflurane; lidocaine; nitrous oxide; norepinephrine; parasympathetic nervous system; phenylephrine; sympathetic nervous system; vascular smooth muscle

Desflurane is a new, potent, inhaled anesthetic agent that has a very low solubility in blood which permits rapid anesthetic induction and awakening. Recent observations in our lab suggest that the administration of desflurane produces marked sympathetic activation resulting in substantial tachycardia and hypertension. In addition, published data from patients with coronary artery disease receiving desflurane demonstrated an unusually high incidence of tachycardia, hypertension and myocardial ischemia. These observations raise the possibility that desflurane might adversely influence the myocardial O2 supply/demand ratio. It is currently unknown if the co-administration of adjuvant drugs (e.g. opioids or nitrous oxide) during desflurane anesthesia favorably modifies the cardiovascular effects of desflurane. It also is uncertain how the neurocirculatory responses to desflurane are altered by age, yet this knowledge would seem to be essentIal prior to desflurane's widespread use. Through this series of studies a more thorough understanding of the autonomic and cardiovascular effects of desflurane will be established. I hypothesize that desflurane activates the sympathetic nervous system and alters baroreceptor reflex control of the circulation, and that these effects are modified in important and reproducible ways by co- administration of common anesthetic adjuvants and by the aging process. The proposed studies will compare and contrast equi-potent concentrations of desflurane and isoflurane. Sympathetic outflow will be directly recorded by sympathetic microneurography and parasympathetic outflow to the heart will be indirectly evaluated by spectral analysis of heart rate variability. In addition, measurements of HR, arterial, central venous and pulmonary artery pressures, norepinephrine levels, forearm arterial blood flow (FBF) and forearm venous compliance (FVC) will be employed to compare the neurocirculatory effects of these two anesthetics. Lower body negative pressure, neck suction/neck pressure and infusions of sodium nitroprusside and phenylephrine will be employed to evaluate cardiopulmonary and arterial baroreflex function while the cold pressor test will be employed to elicit nonbaroreceptor perturbations in autonomic activity. The effects of normal aging and adjuvant drugs (fentanyl, nitrous oxide and topical anesthesia with lidocaine) on the neurocirculatory responses to desflurane will be determined. Finally, the direct effects of desflurane on FBF and FVC will be determined in sympathetically-denervated limbs of spinal cord injured patients. Through these series of studies, a more thorough understanding of the neurocirculatory effects of desflurane will be established. Such knowledge may prove crucial in providing safe anesthesia with desflurane to a diverse population of surgical candidates.

Desflurane是一种新的，有效的吸入麻醉剂，其低点 血液中溶解度允许快速麻醉诱导和 唤醒。我们实验室中的最新观察表明，政府 Desflurane产生明显的交感神经激活，导致 大量心动过速和高血压。此外，发布了来自 患有冠状动脉疾病的患者表现出 心动过速，高血压和心肌的发病率异常高 缺血。这些观察结果提出了Desflurane可能的可能性 不利影响心肌O2供需比。目前是 尚不清楚辅助药物是否共同给药（例如阿片类药物或 在氟烷麻醉期间，一氧化二氮）有利地修饰 Desflurane的心血管效应。这也不确定如何 对Desflurane的神经循环反应随着年龄而改变，但 在Desflurane广泛使用之前，知识似乎是必不可少的。 通过这一系列研究，对 将建立Desflurane的自主神经和心血管效应。我 假设Desflurane激活了交感神经系统和 改变对循环的压力感受器反射控制，这些控制 效果通过共同的重要和可重复的方式修改 使用常见麻醉佐剂和衰老过程。 拟议的研究将比较和对比性浓度 Desflurane和异氟烷。同情流出将直接 通过交感性微功能学和副交感神经流出记录 心脏的光谱分析将间接评估心脏 可变性。另外，人力资源，动脉，中央静脉和 肺动脉压，去甲肾上腺素水平，前臂动脉血 流量（FBF）和前臂静脉合规性（FVC）将用于比较 这两种麻醉药的神经循环作用。 下半身 负压，颈部吸力/颈部压力和钠的输注 硝丙胺和苯肾上腺素将用于评估 冷压力时心肺和动脉压力反射功能 测试将用于引起自主神经中的非杠杆受体扰动 活动。正常衰老和辅助药物的影响（芬太尼， 一氧化二氮和利多卡因的局部麻醉） 将确定对Desflurane的神经循环反应。 最后， Desflurane对FBF和FVC的直接影响将在 脊髓损伤患者的交感性肢体。通过 这些系列研究，对 将建立Desflurane的神经循环作用。这样的知识 可能证明对提供安全的麻醉至关重要 多样化的手术候选人。