Mechanisms of the reflexive respiratory suppression induced by thin-fiber muscular afferents under low O2 and high CO2 environments.

本研究评价了有害气体环境对伤害性输入引起的呼吸负反馈的影响。在麻醉、人工通气的猫中，持续监测其动脉气体张力，研究了不同气体张力引起的不同呼吸水平下薄纤维肌肉传入神经对电刺激的呼吸反应。呼吸输出量由膈神经放电量估计，并以个体猫CO<@D22@>D2反应曲线的第一个拐点（标准点）进行标准化。在标准点的呼吸被方便地称为控制水平。与对照组（呼气末CO<@D22@>D2: 4.3(]SY.+- . [)0.2%， O<@D22@>D2: 20）相比，低CO<@D22@>D2（呼气末10.0(]SY.+- . [)0.4%, n=4）或高CO<@D22@>D2张力（呼气末6.0(]SY.+- . [)0.3%, n=10）呼吸水平增强时，反射性呼吸抑制程度减弱。…多5个（[]SY.+- .[] 0.3%）。因此，我们认为，增强的呼吸前刺激水平的促进成分克服了过度传入输入引起的抑制成分。反射性呼吸抑制被认为是由内源性阿片能系统介导的。我们测量了脑干尾部脑脊液中的-内啡肽，脑脊液是控制呼吸功能的物质。有害气体环境（吸入8% O_2 （n=5）或6% CO_2(=5)）没有引起ELISA测定的β -内啡肽样免疫反应性的一致变化。在高CO<@D22@>D2张力的呼吸增强水平（呼气末6.0(]SY.+- . [) 0.4%, n=6）下，与对照组（呼气末4.7(]SY.+- . [) 0.4%, n=6）相比，吗啡引起的呼吸抑制（i. v.）的幅度有减小的趋势。这一结果意味着，增强的呼吸前刺激水平的促进成分克服了外源性阿片类药物引起的抑制成分，正如反射性呼吸抑制所表明的那样。综上所述，有毒气体环境可能影响阿片类药物的作用效力，而不是释放。少

Present study evaluated influences of noxious gas-environment on respiratory negative feedback induced by nociceptive input. In anesthetized, artificially ventilated cats in which arterial gas tensions were continuously monitored, respiratory response to electrical stimulation of thin-fiber muscular afferents was studied at different levels of respiration induced by different gas tensions. Respiratory outputs was estimated from phrenic nerve discharges and standardized by the first inflection point (standard point) of CO<@D22@>D2 response curve of individual cat. The respiration at the standard point is conveniently referred to as control level. At the augmented levels of respiration by low O<@D22@>D2 (end-expiratory 10.0(]SY.+-。[)0.4%, n=4) or high CO<@D22@>D2 tension (end-expiratory 6.0(]SY.+-。[)0.3%, n=10) the magnitudes of the reflexive respiratory suppression were attenuated, compared with those at the control level (end-expiratory CO<@D22@>D2 : 4.3(]SY.+-。[)0.2%, O<@D22@>D2 : 20. … More 5(]SY.+-。[)0.3%, respectively). Thus it is considered that the facilitatory component of the augmented pre-stimulus level of respiration overcome the inhibitory component induced by excessive afferent input.The reflexive respiratory suppression is thought to be mediated by endogenous opioidergic system. We measured beta-endorphine in cerebrospinal perfusate of caudal part of brainstem region, which is known to control respiratory function. Noxious gas-environment (inhalation of either 8 % O_2 (n=5) or 6 % CO_2 (=5)) did not induce any consistent changes in beta-endorphine-like immunoreactivities measured by ELISA.At the augmented levels of respiration by high CO<@D22@>D2 tension (end-expiratory 6.0(]SY.+-。[)0.4 %, n=6) the magnitudes of the respiratory depression induced by morphine (i. v.) tended to decrease, compared with those at control level (end-expiratory 4.7(]SY.+-。[)0.4 %, n=6). This result would mean that the facilitatory component of the augmented pre-stimulus level of respiration overcame the inhibitory component induced by administration of exogenous opioid, as suggested for the reflexive respiratory suppression. In conclusion noxious gas-environment may influence potency of action, not release, of opioid. Less