Petrozzino J J, Scardella A T, Santiago T V, Edelman N H
Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903.
J Appl Physiol (1985). 1992 Feb;72(2):590-6. doi: 10.1152/jappl.1992.72.2.590.
Inspiratory flow-resistive loading (IRL) in unanesthetized goats causes central elaboration of endogenous opioids, which is accompanied by inhibition of several respiratory muscles. The peripheral stimulus responsible for mediating this phenomenon is unknown. We hypothesized that lactic acid mediates release of endogenous opioids during IRL. Unanesthetized goats were pretreated with either saline or dichloroacetate (DCA; 50 mg/kg iv), a blocker of lactic acid formation, and subjected to IRL (50 cmH2O.l-1.s) for 120 min followed by naloxone (NLX; 0.3 mg/kg iv). Electromyographic activities of the diaphragm (EMGdi), external oblique (EMGeo), and external intercostal (EMGei) were measured and expressed as a percentage of activity at an end-tidal CO2 of 8%. DCA blocked the NLX-induced augmentation of all EMGs observed after 120 min of IRL as follows (means +/- SE): delta EMGdi from 20.8 +/- 5.6% (saline) to 1.2 +/- 2.7% (DCA), delta EMGeo from 116.6 +/- 30.9% (saline) to 5.3 +/- 11.4% (DCA), and delta EMGei from 43.8 +/- 11.3% (saline) to -4.5 +/- 5.6% (DCA) (all P less than 0.05, DCA vs. saline). We conclude that lactic acid produced by the contracting respiratory muscles is the stimulus responsible for endogenous opioid pathway activation during IRL.
未麻醉山羊的吸气性气流阻力负荷（IRL）会引起内源性阿片类物质在中枢的释放，同时伴有几块呼吸肌的抑制。介导这一现象的外周刺激尚不清楚。我们假设乳酸在IRL期间介导内源性阿片类物质的释放。给未麻醉的山羊预先注射生理盐水或二氯乙酸（DCA；50mg/kg静脉注射），后者是一种乳酸生成阻滞剂，然后对其进行120分钟的IRL（50cmH₂O·l⁻¹·s），随后注射纳洛酮（NLX；0.3mg/kg静脉注射）。测量膈肌（EMGdi）、腹外斜肌（EMGeo）和肋间外肌（EMGei）的肌电图活动，并表示为呼气末二氧化碳为8%时活动的百分比。DCA阻断了IRL 120分钟后观察到的NLX诱导的所有肌电图活动增强，如下所示（平均值±标准误）：EMGdi的变化从20.8±5.6%（生理盐水组）降至1.2±2.7%（DCA组），EMGeo的变化从116.6±30.9%（生理盐水组）降至5.3±11.4%（DCA组），EMGei的变化从43.8±11.3%（生理盐水组）降至-4.5±5.6%（DCA组）（所有P<0.05，DCA组与生理盐水组相比）。我们得出结论，收缩的呼吸肌产生的乳酸是IRL期间内源性阿片类途径激活的刺激因素。
