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Toxicologic Pathology
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Journal Article

Histomorphogenesis of Soman-Induced Encephalocardiomyopathy in Sprague-Dawley Rats

Leander Tryphonas

Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ontario, Canada

John G. Clement

Biomedical Defence Section, Defence Research Establishment Suffield, Ralston, Alberta, Canada

Although myocardial damage caused by soman has been previously reported, its relation to brain damage is unclear. In order to clarify this relationship, we examined the histomorphogenesis of central nervous system (CNS) and myocardial lesions in Sprague-Dawley rats, given atropine methylnitrate (20 mg/kg) and HI-6 (125 mg/kg) ip 10 min before a single injection of 0 or 130 µg soman/kg (sc) and sacrificed 45 min and 1.5 hr, 3 hr, 24 hr, and 72 hr later. Bilaterally symmetrical CNS damage began with vacuolation of the neuropil and was followed by astrocytic degeneration and neuronal necrosis culminating in liquefaction necrosis and focal hemorrhage. The cerebral cortex, limbic system, thalamus, and substantia nigra were common target sites. Repair in affected sites was characterized by capillary endothelial cell proliferation, microgliosis, and reversal of microvacuolation. Myocardial damage began with myocytolysis and contraction bands and evolved into coagulative myocytolysis and replacement fibrosis with a transient recruitment of acute inflammatory cells. The left ventricle, especially its free wall and papillary muscles, was consistently affected. There was good correlation among seizures, CNS damage, and myocardial lesions at all times following treatment. The results support the view that CNS lesions are associated with protracted seizure activity and provide evidence that myocardial damage is neurogenic.

Key Words: Brain hemorrhage • catecholamines • cholinesterase inhibitors • encephalocardiomyopathy • hydrocephalus • myocardial fibrosis • myocytolysis • soman (pinacolyl methylphosphonofluoridate) • toxic encephalopathy • toxic cardiomyopathy

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Toxicologic Pathology, Vol. 23, No. 3, 393-409 (1995)
DOI: 10.1177/019262339502300316
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 Toxicol PatholHome page
L. Tryphonas, J. P. Veinot, and J. G. Clement
Early Histopathologic and Ultrastructural Changes in the Heart of Sprague-Dawley Rats Following Administration of Soman
Toxicol Pathol, March 1, 1996; 24(2): 190 - 198.
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