A Subregion of the Parabrachial Nucleus Partially Mediates Respiratory Rate Depression from Intravenous Remifentanil in Young and Adult Rabbits. Anesthesiology 2017 Sep;127(3):502-514
Date
06/08/2017Pubmed ID
28590302Pubmed Central ID
PMC5561451DOI
10.1097/ALN.0000000000001719Scopus ID
2-s2.0-85020254103 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
BACKGROUND: The efficacy of opioid administration to reduce postoperative pain is limited by respiratory depression. We investigated whether clinically relevant opioid concentrations altered the respiratory pattern in the parabrachial nucleus, a pontine region contributing to respiratory pattern generation, and compared these effects with a medullary respiratory site, the pre-Bötzinger complex.
METHODS: Studies were performed in 40 young and 55 adult artificially ventilated, decerebrate rabbits. We identified an area in the parabrachial nucleus where α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid microinjections elicited tachypnea. Two protocols were performed in separate sets of animals. First, bilateral microinjections of the μ-opioid receptor agonist [D-Ala, N-MePhe, Gly-ol]-enkephalin (100 μM) into the "tachypneic area" determined the effect of maximal μ-opioid receptor activation. Second, respiratory rate was decreased with continuous IV infusions of remifentanil. The opioid antagonist naloxone (1 mM) was then microinjected bilaterally into the "tachypneic area" of the parabrachial nucleus to determine whether the respiratory rate depression could be locally reversed.
RESULTS: Average respiratory rate was 27 ± 10 breaths/min. First, [D-Ala, N-MePhe, Gly-ol]-enkephalin injections decreased respiratory rate by 62 ± 20% in young and 45 ± 26% in adult rabbits (both P < 0.001). Second, during IV remifentanil infusion, bilateral naloxone injections into the "tachypneic area" of the parabrachial nucleus reversed respiratory rate depression from 55 ± 9% to 20 ± 14% in young and from 46 ± 20% to 18 ± 27% in adult rabbits (both P < 0.001). The effects of bilateral [D-Ala, N-MePhe, Gly-ol]-enkephalin injection and IV remifentanil on respiratory phase duration in the "tachypneic area" of the parabrachial nucleus was significantly different from the pre-Bötzinger complex.
CONCLUSIONS: The "tachypneic area" of the parabrachial nucleus is highly sensitive to μ-opioid receptor activation and mediates part of the respiratory rate depression by clinically relevant administration of opioids.
Author List
Miller JR, Zuperku EJ, Stuth EAE, Banerjee A, Hopp FA, Stucke AGAuthors
Anjishnu Banerjee PhD Associate Professor in the Institute for Health and Equity department at Medical College of WisconsinAstrid G. Stucke MD Professor in the Anesthesiology department at Medical College of Wisconsin
Eckehard A. Stuth MD Professor in the Anesthesiology department at Medical College of Wisconsin
Edward J. Zuperku PhD Professor in the Anesthesiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Analgesics, OpioidAnimals
Disease Models, Animal
Female
Male
Parabrachial Nucleus
Piperidines
Rabbits
Respiratory Insufficiency
Respiratory Rate
