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Contribution Of The Pontine Medial Parabrachial Nucleus (mPBN) To The Respiratory Depression From The Benzodiazepine Midazolam (MDZ)
Author(s) -
Zuperku Edward J.,
Stucke Astrid G.,
Hopp Francis A.,
Tomlinson Jack,
Krolikowski John G.,
Stuth Eckehard A.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1054.11
Subject(s) - microinjections , damgo , anesthesia , benzodiazepine , opioid , flunitrazepam , chemistry , bicuculline , medicine , pharmacology , enkephalin , gabaa receptor , microinjection , receptor
The risk of hypoventilation and apnea induced by systemic opioids appears to be greatly increased in the presence of sedatives such as MDZ. A subregion within the mPBN plays a key role in the control of expiratory duration (TE) and in addition, systemic opioid‐induced bradypnea can be reversed by naloxone microinjections in this subregion. We hypothesized that the enhanced depression of breathing may be due an enhanced GABAergic inhibition by MDZ in this subregion. The responses of phrenic nerve activity (PNA) to microinjections of MDZ (100 μM; 360 nl) and the mu‐opioid agonist [D‐Ala 2 , N‐MePhe 4 , Gly‐ol]‐enkephalin (DAMGO, 100 μM, 360 nl) into the mPBN subregion were compared in decerebrate, ventilated, vagotomized dogs. Responses to microinjected AMPA were used to identify the tachypneic subregion. Microinjections of MDZ had no effect on inspiratory duration (TI), TE, peak PNA, whereas DAMGO microinjections increased TE (by 85±48%; n=10), slightly increased TI and had no effect on peak PNA. Intravenous administration of MDZ produced a dose‐dependent reduction in TI (−18.5±4.5%) and peak PNA (−29.0±4.1%) with a small non‐significant increase in TE (n=13; peak dose: 238±10 μg/kg). Thus, the respiratory depressant effects of systemic MDZ on breathing do not appear to be mediated by the mPBN subregion where opioids induce bradypnea. Support or Funding Information Supported by VA grant 2 I01BX000721‐06.