Neurophysiological concomitants of soman-induced respiratory depression in awake, behaving guinea pigs

Chang, Fat-Chun Tony; Foster, Robert E.; Beers, Everette T.; Rickett, D. L.; Filbert, Margaret G.

doi:10.1016/0041-008x(90)90023-n

Cited by 52 publications

(32 citation statements)

References 34 publications

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“…Acute effects of poisoning include central apnea [1][2][3][4], seizures [5,6], bronchorrhea, bronchoconstriction, muscle weakness, myosis, urination, and salivation [7][8][9][10]. The morbidity and mortality from acute OP poisoning is attributed to respiratory failure [11] but the relative contributions of the central and peripheral effects in producing collapse of the respiratory system [12] is unclear.…”

Section: Introductionmentioning

confidence: 99%

Pathophysiology of respiratory failure following acute dichlorvos poisoning in a rodent model

Gaspari

Paydarfar

2007

NeuroToxicology

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INTRODUCTIONOrganophosphate (OP) poisoning produces a cholinergic crisis by blockade of acetylcholinesterase in the central and peripheral nervous systems. Acute effects of poisoning include central apnea [1][2][3][4], seizures [5,6], bronchorrhea, bronchoconstriction, muscle weakness, myosis, urination, and salivation [7][8][9][10]. The morbidity and mortality from acute OP poisoning is attributed to respiratory failure [11] but the relative contributions of the central and peripheral effects in producing collapse of the respiratory system [12] is unclear. The clinical literature emphasizes the peripheral effects contributing to acute pulmonary insufficiency [11,13]. However this does not exclude early mortality in the field due to central apnea [14,15].In this study we used a rodent model to analyze the dynamics of respiratory and cardiovascular collapse during acute OP poisoning. We found that poisoning caused a rapidly lethal central apnea. Central apnea consistently occurred soon after the poisoning but pulmonary insufficiency was more variable in both timing and severity. Mortality was reduced in animals that were sustained solely by artificial ventilation; however most ventilated animals exhibited signs of impaired gas exchange due to pulmonary insufficiency. Our findings support the hypothesis that OP poisoning in this animal model causes a sequential "two hit" insult, with rapid central apnea followed by delayed impairment of pulmonary gas exchange with prominent airway secretions. MATERIALS AND METHODSWe studied 27 male Wistar rats, weighing 275-325 gm (Charles River Laboratories, Wilmington, MA). The University of Massachusetts Medical School Institutional Animal Care and Utilization Committee approved all experimental procedures and protocols. The animal model used in this study is a novel preparation for OP research and the procedures are described in detail below.Corresponding Author: Romolo J Gaspari, MD, MSc, Assistant Professor, Department of Emergency Medicine, University of Massachusetts School of Medicine, 55 Lake Ave North, Worcester, MA 01655, Phone -508-334-7943, Fax -508-421-1490, Gasparir@UMMHC.org, Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Surgical ProceduresSurgical procedures were performed under general anesthesia with 1.5 -2.2% isoflurane (Abbott Labs, North Chicago, IL) titrated to achieve a respiratory rate of 50-60 breaths per minute. All surgical procedures were performed under 100% oxygen. The animals were restrained in a supine position with the head extended and limbs abducted. Adequacy of anesthesia was confir...

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Section: Introductionmentioning

confidence: 99%

Pathophysiology of respiratory failure following acute dichlorvos poisoning in a rodent model

Gaspari

Paydarfar

2007

NeuroToxicology

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“…Because soman has been shown to be a potent central respiratory depressant (2,12,56), initially it was thought that soman-induced pathology was due to hypoxia. Recently it was suggested that neither the nerve agent-induced seizure activity per se nor the direct toxic actions of the nerve agent appear to be responsible for the nerve agent induced neuropathology, supporting the coparticipation of a noncholinergic mechanism (29,36,37,(39)(40)(41)45).…”

Section: Introductionmentioning

confidence: 99%

Histomorphogenesis of Soman-Induced Encephalocardiomyopathy in Sprague-Dawley Rats

Tryphonas

Clement²

1995

Toxicol Pathol

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“…26 The dissociation of central respiratory timing mechanisms described by Chang and coworkers'" also may be a factor in pro- gressive respiratory depression. That the majority ofthe animals receiving GB became apneic despite observed ongoing peripheral muscle activity during the apneic state provides further support for a central origin of the respiratory failure.…”

Section: Discussionmentioning

confidence: 99%

A Comparison of the Effects of Sarin and Succinylcholine on Respiratory Parameters in Anesthetized Domestic Swine

Duncan¹,

Conley²,

Grychowski³

et al. 2001

Military Medicine

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Differences in the "respiratory paralysis" caused by sarin (GB) and succinylcholine (SDC) were observed in a domestic swine model using a bedside pulmonary dynamics monitor. GB was administered intravenously (9 JLglkg/30 min) and compared with SDC administered intravenously (20 mg/30 min). All animals developed respiratory insufficiency indicated by decreased respiratory frequency. Minute ventilation was relatively maintained in animals that received GB by increasing tidal volume, whereas both of these parameters decreased in animals that received SDC. GBanimals showed an increase in airway resistance and work of breathing. The former was unchanged and the latter was decreased in animals that received SDC. Mouth occlusion pressure at 100 milliseconds and tidal volume were relatively maintained in GB animals but decreased in SDC animals, suggesting a central mechanism for respiratory paralysis with GB and a peripheral mechanism for respiratory paralysis with SDC.

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Neurophysiological concomitants of soman-induced respiratory depression in awake, behaving guinea pigs

Cited by 52 publications

References 34 publications

Pathophysiology of respiratory failure following acute dichlorvos poisoning in a rodent model

Pathophysiology of respiratory failure following acute dichlorvos poisoning in a rodent model

Histomorphogenesis of Soman-Induced Encephalocardiomyopathy in Sprague-Dawley Rats

A Comparison of the Effects of Sarin and Succinylcholine on Respiratory Parameters in Anesthetized Domestic Swine

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