title: Respiratory muscle acidosis stimulates endogenous opioids during inspiratory loading.
abstract: Activation of endogenous opioid pathways during intense inspiratory flow-resistive loading (IRL) results in greater inhibition of EMG activity in the external oblique (EMGeo) relative to the diaphragm (EMGdi). Dichloroacetate (DCA) abolishes opioid-mediated inhibitory influences upon these muscles, suggesting a causal relationship between respiratory muscle lactic acidosis and activation of endogenous opioid pathways, during IRL. We tested the hypothesis that a more intense acidosis of the external oblique relative to the diaphragm may be the signal that determines the differential inhibitory opioid-mediated effect upon the respiratory muscles during IRL. Unanesthetized goats were exposed to IRL (50 cm H2O/1/s) for 120 min, before and after intravenous pretreatment with DCA (50 mg/kg) or saline. We measured peak phasic EMGdi and EMGeo, and respective muscle interstitial pH (pHdi, pHeo) using flexible pH probes. After 120 min IRL with saline, pHdi, and pHeo declined by -0.12 +/- 0.03 (mean +/- SEM) and -0.20 +/- 0.04 units, respectively (p < 0.05, pHdi versus pHeo). Naloxone (NLX), 0.3 mg/kg given intravenously at this time, increased EMGdi by 26.5 +/- 6.1%, but EMGeo by 81.9 +/- 13.3% (p < 0.05, EMGdi versus EMGeo). DCA blunted both the change in pHdi and pHeo during IRL (to -0.01 +/- 0.01 and -0.08 +/- 0.03 units, respectively) (p < 0.05, DCA versus saline) and the increase in EMGdi and EMGeo with NLX (to -1.0 +/- 2.6% and 5.7 +/- 5.8%, respectively) (p < 0.05, DCA versus saline).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903-0019.
authors.forename: J J
authors.initials: JJ
authors.lastname: Petrozzino
authors.forename: A T
authors.initials: AT
authors.lastname: Scardella
authors.forename: N H
authors.initials: NH
authors.lastname: Edelman
authors.forename: T V
authors.initials: TV
authors.lastname: Santiago
mesh_terms: D000140:Acidosis, Lactic / Q000378:metabolism*; D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D003999:Dichloroacetic Acid / Q000494:pharmacology; D004576:Electromyography / Q000187:drug effects; D004723:Endorphins / Q000378:metabolism*; D006041:Goats; D006863:Hydrogen-Ion Concentration; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects / Q000502:physiology*; D012132:Respiratory Muscles / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
chemical_list: D004723:Endorphins; D002245:Carbon Dioxide; D009270:Naloxone; D003999:Dichloroacetic Acid