PMID- 33785355
OWN - NLM
STAT- MEDLINE
DCOM- 20210511
LR  - 20240226
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 419
DP  - 2021 May 15
TI  - Efficacy of atropine and scopolamine on airway contractions following exposure to 
      the nerve agent VX.
PG  - 115512
LID - S0041-008X(21)00119-8 [pii]
LID - 10.1016/j.taap.2021.115512 [doi]
AB  - Nerve agents are highly toxic organophosphorus compounds that inhibit 
      acetylcholinesterase resulting in rapid accumulation of the neurotransmitter 
      acetylcholine (ACh) causing a cholinergic syndrome including respiratory failure. 
      In the present study, respiratory responses and antimuscarinic treatment efficacy 
      was evaluated ex vivo using rat precision-cut lung slices (PCLS) exposed to the 
      nerve agent VX. The respiratory effects were evaluated either by adding exogenous 
      ACh directly to the culture medium or by applying electric-field stimulation 
      (EFS) to the PCLS to achieve a release of endogenous ACh from neurons in the lung 
      tissue. The airway contraction induced by both methods was enhanced by VX and 
      resulted in lingering airway recovery, in particular when airways were exposed to 
      a high VX-dose. Both contractions induced by EFS and exogenously added ACh were 
      significantly reduced by administration of the antimuscarinic drugs atropine or 
      scopolamine. Two additions of atropine or scopolamine after maximal ACh-induced 
      airway response was demonstrated effective to reverse the contraction. By adding 
      consecutive doubled doses of antimuscarinics, high efficiency to reduce the 
      cholinergic airway response was observed. However, the airways were not 
      completely recovered by atropine or scopolamine, indicating that non-muscarinic 
      mechanisms were involved in the smooth muscle contractions. In conclusion, it was 
      demonstrated that antimuscarinic treatment reversed airway contraction induced by 
      VX but supplemental pharmacological interventions are needed to fully recover the 
      airways. Further studies should therefore clarify the mechanisms of physiological 
      responses in lung tissue following nerve agent exposures to improve the medical 
      management of poisoned individuals.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Wigenstam, E
AU  - Wigenstam E
AD  - Swedish Defence Research Agency, CBRN Defence and Security, Umea, Sweden.
FAU - Forsberg, E
AU  - Forsberg E
AD  - Swedish Defence Research Agency, CBRN Defence and Security, Umea, Sweden.
FAU - Bucht, A
AU  - Bucht A
AD  - Swedish Defence Research Agency, CBRN Defence and Security, Umea, Sweden.
FAU - Thors, L
AU  - Thors L
AD  - Swedish Defence Research Agency, CBRN Defence and Security, Umea, Sweden. 
      Electronic address: lina.thors@foi.se.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210327
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (Muscarinic Antagonists)
RN  - 0 (Organothiophosphorus Compounds)
RN  - 7C0697DR9I (Atropine)
RN  - 9A4381183B (VX)
RN  - DL48G20X8X (Scopolamine)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
RN  - EC 3.1.1.7 (Ache protein, rat)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/metabolism/pharmacology
MH  - Acetylcholinesterase/metabolism
MH  - Animals
MH  - Atropine/*pharmacology
MH  - Cholinergic Fibers/*drug effects/enzymology
MH  - Cholinesterase Inhibitors/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Electric Stimulation
MH  - Female
MH  - GPI-Linked Proteins/antagonists & inhibitors/metabolism
MH  - Lung/*innervation
MH  - Muscarinic Antagonists/*pharmacology
MH  - Muscle Contraction/*drug effects
MH  - Muscle, Smooth/*innervation
MH  - Organothiophosphorus Compounds/*toxicity
MH  - Rats, Sprague-Dawley
MH  - Scopolamine/*pharmacology
MH  - Rats
OTO - NOTNLM
OT  - Airway contractions
OT  - Antimuscarinics
OT  - Cholinergic responses
OT  - Nerve agents
OT  - Precision-cut lung slices
EDAT- 2021/04/01 06:00
MHDA- 2021/05/12 06:00
CRDT- 2021/03/31 05:53
PHST- 2021/01/11 00:00 [received]
PHST- 2021/03/10 00:00 [revised]
PHST- 2021/03/25 00:00 [accepted]
PHST- 2021/04/01 06:00 [pubmed]
PHST- 2021/05/12 06:00 [medline]
PHST- 2021/03/31 05:53 [entrez]
AID - S0041-008X(21)00119-8 [pii]
AID - 10.1016/j.taap.2021.115512 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2021 May 15;419:115512. doi: 10.1016/j.taap.2021.115512. 
      Epub 2021 Mar 27.