A sublethal dose of sarin (GB, isopropyl methylphosphonofluoridate) was administered to mice. The animals were killed up to 28 d after dosing and frozen sections were made of the excised diaghragms which were stained using haematoxylin and eosin and a modified Gomori trichrome method. Muscle fibre degeneration and mononuclear infiltration were seen, notably at 24 h and 3 d. A number of histochemical procedures were carried out, including the GBHA procedure for ionized calcium. Calcium accumulation, seen at 4 h, was the earliest abnormality observed. All changes were rapidly regressing by 5 d and histological appearances were normal by 14 d. It was concluded that sarin produced myopathic changes preceded by calcium accumulation.
Get full access to this article
View all access options for this article.
References
1.
' Ariens AT; Wolthuis OL & van Bentham Rmj.Reversible necrosis at the end plate region in striated muscles of the rat poisoned with cholinesterase inhibitors. Experientia1969; 1: 57-9.
2.
Wecker L. & Dettbarn W-D.Paraoxon-induced myopathy: muscle specifity and acetylcholine involvement. ExperimentalNeurology1978; 51: 281-91.
3.
Wecker L., Kiauta T. & Dettbarn W-D.Relationship between acetylcholinesterase inhibition and the development of a myopathy. Journal of Pharmacology and Experimental Therapeutics1978; 206: 97-104.
4.
Leonard JP & Salpeter MMAgonist induced myopathy at the neuromuscular junction is mediated by calcium. Journal ofCell Biology1979; 82: 811-19.
5.
Dettbarn W-D.Pesticide-induced muscle necrosis: mechanisms and prevention. Fundamental and Applied Toxicology1984; 4: S18-S26.
6.
Gupta RC, Patterson, GT & Detbarn W-D.Acute tabun toxicity; biochemical and histochemical consequences in brain and skeletal muscles of rat. Toxicology1987 ; 46: 329-41.
7.
Gupta RC, Patterson GT & Dettbarn W-D.Biochemical and histochemical alterations following acute soman intoxication in the rat. Toxicology and Applied Pharmacology1987; 87: 393-402.
8.
De Rueck J. & Willems J.Acute parathion poisoning: myopathic changes in the diaphragm. Journal of Neurology1975; 208: 309-14.
9.
Wecker L., Mrak RE & Dettbarn W-D.Evidence of necrosis in human intercostal muscle following inhalation of an organophosphate insecticide. Toxicology and Applied Pharmacology1986; 6: 172-4.
10.
Pimentel JM & Carrington da Costa RBEffects of organophosphorus poisoning on the heart. In Toxicology of organophosphates and carbamates, eds, B Ballantyne and TC Marrs.Sevenoaks: Butterworths , in press.
11.
" Duncan CJRole of intracellular calcium in promoting muscle damage: a strategy for controlling the dystrophic condition. Experientia1978 ; 43: 1531-672.
12.
Marrs TC, Bright JE, Inns RH & Tuckwell NJHistochemically-demonstrated calcium influx into mouse diaphragms induced by sarin. Toxicologist1990; 10: 132.
13.
Inns RH, Tuckwell NJ, Bright JE & Marrs TCHistochemical demonstration of calcium accumulation in muscle fibres after experimental organophosphate poisoning. Human and Experimental Toxicology1990; 9: 245-50.
14.
Drury Rab & Wallington EACarleton's Histological Technique, p. 129. Oxford: Oxford University Press, 1969.
15.
Brumback RA & Leech RWColor Atlas of Muscle Histochemistry, p. 30. Littleton, Massachusetts: PSG, 1984.
16.
Karnovsky MJ & Roots L.A direct method for cholinesterase . Journal of Histochemistry and Cytochemistry1964; 12: 210-21.
17.
Kashiwa HK & Atkinson WBThe applicability of a new Schiff base, glyoxyl bis (2-hydroxy-anil) for the cytochemical localisation of ionic calcium. Journal of Histochemistry and Cytochemistry1963; 11: 258-64.
18.
Bancroft JD & Hand NMRoyal Microscopical Society Handbook: 14. Enzyme histochemistry, p. 39. Oxford: Oxford University Press, 1959.
19.
Brown J.Report on work undertaken in the Pathology and Clinical Toxicology Section , Medical Division, CDE Porton Down, 1989.
20.
Reichamnn H. & Pette D.A comparative micromorphometric study of succinate dehydrogenase activity levels in Type I, IIA and IIB fibres of mammalian and human muscles. Histochemistry1982; 74: 27-41.
21.
Gorza L.Identification of a novel type 2 fiber population in mammalian skeletal muscle by combined use of histochemical myosine ATPase and anti-myosin monoclonal antibodies. Journal of Histochemistry and Cytochemistry1990; 38: 257-65.
22.
Drury Rab & Wallington EACarleton's Histological Technique, p. 207. Oxford: Oxford University Press, 1969.
23.
Barka T.A simple azo dye method for histochemical demonstration of acid phosphatase . Nature1960; 187: 248-9.
Duance VC, Black C., Dubowitz V., Hughes Grv & Bailey AJPolymyositis - an immunofluorescence study on the distribution of collagen types. Muscle and Nerve1980; 3: 487-90.
26.
Stephens HR , Duance VC, Dunn MJ, Bailey AJ & Dubowitz V.Collagen types in neuromuscular disease. Journal of Neurological Sciences1982; 53: 45-62.
27.
Preusser H-J.Die Ultrastruktur der motorischen Endplatte im Zwerchfell der Ratte und Veränderungen nach Inhibierung der Acetylcholinesterase . Zeitschrift fiir Zellforschung1967; 80: 436-57.
