The Failure of Respiration in Death by Anticholinesterase Poisoning

Candole, C. A. De; Douglas, W. W.; Evans, C. Lovatt; Holmes, R.; Spencer, K. E. V.; Torrance, R. W.; Wilson, Kathy

doi:10.1111/j.1476-5381.1953.tb01350.x

Cited by 117 publications

(53 citation statements)

References 11 publications

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“…The same applies to tetraethyl pyrophosphate (TEPP) poisoning in cats (22). As already mentioned, soman is a typical example of predominantly centrally acting anticholinesterase nerve agents, where the activity of respiratory centre is impaired first, followed by the neuromuscular transmission and pulmonary muscarinic syndrome, which is of definitely least clinical significance (14). At the same time, TEPP and sarin in rabbits first affect the neuromuscular transmission and then cause a respiratory arrest (21).…”

Section: Central Component Of Anticholines Teraseinduced Respiratormentioning

confidence: 99%

“…Although this pulmonary muscarinic syndrome compromises the alveolar gas exchange and lead to hypoxaemia, the results of significant inhibition of AChE in diaphragm and intercostal muscles is considered more serious and more important for survival, although it depends on the animal species studied (14). Anticholinesterases usually in the beginning induce a slight increase in contractions of diaphragm, but longer-lasting surplus of acetylcholine in the vicinity of nicotinic receptors eventually lead to a Wedensky-type of depolarization block (21).…”

Section: Peripheral Component Of Anticholin Esteraseinduced Respiramentioning

confidence: 99%

“…Cause of death in most of the animal species investigated was respiratory failure (14), although is many publications a considerable attention was drawn to the cardiovascular collapse as an independent factor contributing to a lethal outcome (15).…”

Section: Peripheral Versus Central Anticholinesterasesmentioning

confidence: 99%

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Mechanism and Clinical Importance of Respiratory Failure Induced by Anticholinesterases

Ivosevic

Miletić

Vulović

et al. 2017

Serbian Journal of Experimental and Clinical Research

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Section: Central Component Of Anticholines Teraseinduced Respiratormentioning

confidence: 99%

Section: Peripheral Component Of Anticholin Esteraseinduced Respiramentioning

confidence: 99%

See 1 more Smart Citation

Mechanism and Clinical Importance of Respiratory Failure Induced by Anticholinesterases

Ivosevic

Miletić

Vulović

et al. 2017

Serbian Journal of Experimental and Clinical Research

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“…As de Candole, Douglas, Lovatt Evans, Holmes, Spencer, Torrance and Wilson (1953) have pointed out, respiratory failure after systemic sarin poisoning is due partly to central paralysis and partly to paralysis of neuromuscular transmission. It appears from the present results that atropine was fully effective against the central component, but it is well known that atropine in therapeutic doses has no effect on neuromuscular transmission (see tum Suden, 1958).…”

Section: Treatmentmentioning

confidence: 99%

The Effects of Intracisternal Sarin and Pyridine‐2‐aldoxime Methyl Methanesulphonate in Anaesthetized Dogs

Brown¹

1960

British Journal of Pharmacology and Chemotherapy

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Dogs poisoned by the anticholinesterase sarin could be saved by intravenous administration of atropine sulphate together with a suitable oxime. The central effects of intracisternal sarin were respiratory paralysis and vasomotor stimulation. The problem arose as to whether the oxime, being a quaternary nitrogen compound, could enter the brain from the blood, and could have a central action on the paralysed respiration. The methyl methanesulphonate of pyridine-2-aldoxime administered intracisternally, after sarin poisoning by the same route, was ineffective; atropine, given intravenously, was effective. The central and peripheral effects of sarin were thus reversed by the atropine-oxime therapy, the central effects by atropine, the peripheral by the oxime. Dogs given many times the LD50 of the potent anticholinesterase sarin (isopropyl methyl-phosphonofluoridate) can be saved by the intravenous injection of atropine sulphate and the methiodide of pyridine-2-aldoxime. Atropine alone, while re-starting respiration, is incapable of maintaining it (Brown, Kunkel, Somers and Wills, 1957;Wills, Kunkel, Brown and Groblewski, 1957). The oxime alone is ineffective in re-establishing respiration. If the oxime is given 5 min. after the atropine, respiration improves within 0.5 min. which might be compatible with a central effect although quaternary nitrogen compounds penetrate the blood-brain barrier with difficulty (see Koelle and Steiner, 1956).The experiments were undertaken to assess the central effects of sarin and of pyridine-2-aldoxime and the relative importance of central and peripheral paralysis of respiration in poisoning with sarin. METHODSThe sarin was diluted with saline immediately before use and the volume injected was always less than 0.12 ml. Because of its greater solubility and equal efficacy (Davies and Willey, 1958), the methyl methanesulphonate of pyridine 2-aldoxime was used in the present work instead of the methiodide and was administered in aqueous solution containing 100 jug. or 1,000 ,ug./0.1 ml.; both freshly made and *Present address: Chemical Warfare Laboratories, Army Chemical Center, Maryland, U.S.A. older solutions wer used, and were often tested by the copper acetate-benzidine acetate test for the presence of cyanide. The atropine sulphate solution contained 2 mg./ml., and, except as noted, was always given intravenously, 0.5 mg./kg. The dogs were anaesthetized by pentobarbitone sodium given intravenously, enough being administered to abolish the palpebral reflex, thus giving deep surgical anaesthesia. Additional small doses were given as needed. Blood pressure was recorded on a smoked paper by a mercury manometer from a femoral or common carotid artery. The trachea was cannulated. Respirations were recorded by a Marey tambour connected with the tracheal cannula. Artificial respiration (not recorded) was given by a Starling Ideal pump. An external saphenous vein was used for intravenous injections.The dog was placed on its belly and the neck sharply flexed. A midline incision was made wit...

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“…Respiratory failure can be central, peripheral, or a combination of the two (99,100). The predominant site of failure is a functioni of the route of exposure and the species.…”

Section: Ch2-ch2-ci S Ch2-ch2-cimentioning

confidence: 99%

Hazards of chemical weapons release during war: new perspectives.

Reutter

1999

Environ Health Perspect

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The two major threat classes of chemical weapons are mustard gas and the nerve agents, and this has not changed in over 50 years. Both types are commonly called gases, but they are actually liquids that are not re ly voatile. These agents were designed specifically to harm people by any route of exposure and to be effective at low doses. Mustard gas was used in World War I, and the nerve agents were developed shortly before, during, and after World War II. Our perception of the potency of chemical weapons has changed, as well as our concern over potential effects of prolonged exposures to low doses and potential target populations that indude women and cildren. Many of the toxicologic studies and human toxicity esmates for both mustard and nerve agents were designed for the purpose of quickly developing maximal casualties in the least sensitive male soldier. The 'toxcity" of the chemical weapons has not changed, but our perception of 'toxicity" has.

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The Failure of Respiration in Death by Anticholinesterase Poisoning

Cited by 117 publications

References 11 publications

Mechanism and Clinical Importance of Respiratory Failure Induced by Anticholinesterases

Mechanism and Clinical Importance of Respiratory Failure Induced by Anticholinesterases

The Effects of Intracisternal Sarin and Pyridine‐2‐aldoxime Methyl Methanesulphonate in Anaesthetized Dogs

Hazards of chemical weapons release during war: new perspectives.

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