Role of central and peripheral opiate receptors in the effects of fentanyl on analgesia, ventilation and arterial blood-gas chemistry in conscious rats
Role of central and peripheral opiate receptors in the effects of fentanyl on analgesia, ventilation and arterial blood-gas chemistry in conscious rats
复制标题
DOI：
10.1016/j.resp.2013.11.005
复制
发表时间：
2014-01-15
影响因子：
2.3
通讯作者：
Lewis, Stephen J.
中科院分区：
文献类型：
--
作者：
Henderson, Fraser;May, Walter J.;Lewis, Stephen J.
本研究观察了外周限制性阿片受体拮抗剂甲碘纳洛酮(NLXmi)对芬太尼(25 mU g/kg)诱导的清醒大鼠(1)镇痛、(2)动脉血气化学(ABG)和肺泡-动脉压差(A-a)和(3)呼吸参数的影响。1.5 mg/kg的NLXmi对芬太尼引起的镇痛效应影响最小，但5.0 mg/kg的剂量可减弱芬太尼的镇痛效应。芬太尼降低动脉血pH、PO(2)和SO(2)，增加PCO(2)和A-a梯度。NLXMI(1.5 mg/kg)组大鼠的上述反应明显减弱。芬太尼引起呼吸抑制(例如，潮气量和最大吸气流量减少)。静脉注射NLXMI(1.5 mg/kg)。拮抗芬太尼对潮气量的减少，但对其他反应的影响最小。这些结果提示：(1)芬太尼的镇痛和呼吸抑制作用与外周MU有关；(2)NLXmi通过阻断阿片类药物对潮气量和A-a阶差的负性作用而阻断芬太尼对ABG的影响。(C)2013爱思唯尔B.V.保留所有权利。
This study determined the effects of the peripherally restricted mu-opiate receptor (mu-OR) antagonist, naloxone methiodide (NLXmi) on fentanyl (25 mu g/kg, i.v.)-induced changes in (1) analgesia, (2) arterial blood gas chemistry (ABG) and alveolar-arterial gradient (A-a gradient), and (3) ventilatory parameters, in conscious rats. The fentanyl-induced increase in analgesia was minimally affected by a 1.5 mg/kg of NLXmi but was attenuated by a 5.0 mg/kg dose. Fentanyl decreased arterial blood pH, pO(2) and sO(2) and increased pCO(2) and A-a gradient. These responses were markedly diminished in NLXmi (1.5 mg/kg)-pretreated rats. Fentanyl caused ventilatory depression (e.g., decreases in tidal volume and peak inspiratory flow). Pretreatment with NLXmi (1.5 mg/kg, i.v.) antagonized the fentanyl decrease in tidal volume but minimally affected the other responses. These findings suggest that (1) the analgesia and ventilatory depression caused by fentanyl involve peripheral mu-ORs and (2) NLXmi prevents the fentanyl effects on ABG by blocking the negative actions of the opioid on tidal volume and A-a gradient. (C) 2013 Elsevier B.V. All rights reserved.