Male Sprague-Dawley rats were given atropine methylnitrate (20 mg/kg) and HI-6 (125 mg/kg) ip 10 min before a single injection of 130 μg soman/kg sc, and the heart was examined by light and electron microscopy 10, 25, 45, 90, and 180 min after the onset of seizures. Seizures appeared within 6-11 min after treatment. Control rats were given saline sc in place of soman. Early myocardial lesions consisting of hypercontraction and hyperextension of sarcomeres, focal myocytolysis, and contraction bands were detected in individual or groups of myocardial fibers. Hypercontraction was characterized by shortening of the sarcomere length, disappearance of the I and H bands, and thickening of the Z line. In contrast, hyperextended sarcomeres had thickened I and H bands. Myocytolysis was characterized by a progressively severe focal dissolution of myofilaments and edema of the affected sarcoplasmic area. Contraction bands appeared to result from the breakdown of markedly hypercontracted myofibril bundles. Due to the presence of a number of surviving myofilaments and the preservation of the sarcolemmal tube, distortion of the overall myocytic structure was minimal. Changes in the mitochondria and other intracellular organelles were also minimal and nonspecific. The close resemblance of morphologic findings to those induced by catecholamines supports the view that soman-induced myocardial damage is secondary to a treatment-related release of unphysiologic amounts of endogenous catecholamines.
Anichkov SV and Vedeneyeva ZI (1961). Irritation of the sympathetic nerve as a cause of myocardial lesions. Acta Physiol. Hung. 19:17-18.
2.
Ariens AT, Meeter E., and Wolthuis OL (1969). Reversible necrosis at the end-plate region in the striated muscles of the rat poisoned with cholinesterase inhibitors. Experientia25 : 57-59.
3.
Baskin SI and Whitmer MP (1991). The cardiac toxicology of organophosphorus agents . In: Principles of Cardiac Toxicology, SI Baskin (ed). CRC Press, Boca Raton, Florida, pp. 275-293.
4.
Baze WB (1993). Soman-induced morphological changes-An overview in the non-human primate. J. Appl. Toxicol. 13: 173-177.
5.
Baze WB, Anderson DR, Harris LW, Lennox WJ, Bowersox SL, and Solana RP (1991). Soman-induced brain and heart lesions in the rat: Effects of antidotal and anticonvulsant therapy. Proc. 1991 Med. Def. Biosci. Rev. Aug 7-8.
6.
Bloom S. and Cancilla PA (1969). Myocytolysis and mitochondrial calcification after low doses of isoproterenol. Am. J. Pathol. 54: 373-391.
7.
Broomfield CA , Lenz DE, and Maciver B. (1986). The stability of soman and its stereoisomers in aqueous solution: Toxicological considerations . Arch. Toxicol. 59: 261-265.
8.
Burch GE, Sun SC, Colcolough HC, et al (1967). Acute myocardial lesions following experimentally-induced intracranial hemorrhage in mice: A histological and histochemical study. Arch. Pathol. 84: 517-521.
9.
Carpentier P. , Lambrinidis M., and Blanchet G. (1991). Early dendritic changes in hippocampal pyramidal neurones (field CA1) of rats subjected to acute soman intoxication-A light microscopic study. Brain Res. 541: 293-299.
10.
Chappel CL, Rona G., and Balazs T. (1959). Comparison of cardiotoxic actions of certain sympathomimetic amines. Can. J. Biochem. Physiol. 37: 35-42.
11.
Churchill L. , Pazdernik TL, Jackson JL, Nelson SR, McDonough JH, and McLeod CG (1985). Soman induced brain lesions demonstrated by muscarinic receptor autoradiography . NeuroToxicology6: 81-90.
12.
Clement JG and Broxup B. (1993). Efficacy of diazepam and avizafone against soman-induced neuropathology in brain of rats. NeuroToxicology14: 485-504.
13.
Clement JG and Lee MJ (1980). Soman-induced convulsions: Significance of changes in levels of blood erythrocytes, gases, glucose, and insulin. Toxicol. Appl. Pharmacol. 55: 203-204.
14.
DeGroot DMG , Bierman EPB, and Van Huygenvoort AHBM (1990 ). Involvement of acetylcholine and glutamate in soman-induced brain damage. Micron Microscopia Acta21: 247-248.
15.
Filbert MG, Dochterman LW, Smith CD, Forster JS, Phann S., and Cann FJ (1993). Effect of mannitol treatment on soman-induced brain and heart lesions in the rat. Drug. Dev. Res. 30: 45-53.
16.
Fleckenstein A. (1976). Specific inhibitors and promoters of Ca2+ action in the excitation-contraction coupling of heart muscle and their role in the prevention or production of myocardial lesions. In: Calcium and the Heart, P Harris and L Opie (eds). Academic Press, New York, pp. 135-188.
17.
Fleckenstein A., Janke J., Doring HJ, and Leder O. (1974). Myocardial fibre necrosis due to intracellular calcium overload-A new principle in cardiac physiology . Rec. Adv. Struct. Metab. 4: 563-580.
18.
Fleckenstein A., Janke J., Doring HJ, and Pachinger O. (1973). Ca overload as the determinant factor in the production of catecholamine-induced myocardial lesions. Rec. Adv. Stud. Card. Metab. 2: 455-466.
19.
Fleckenstein A., Pachinger O., Leder O., Hein B., and Janke J. (1971). Verhutung isoproterenol-induzierter myocardnekrosen durch senkung der plasmacalcium-speigels mittles calcitonin . Pflugers Arch.332(suppl. 332): R40.
20.
Gibbons WR (1986). Cellular control of cardiac contraction. In: The Heart and Cardiovascular System, HA Fozzard, E HaberRB Jennings, AM Katz , and HE Morgan (eds). Raven Press, New York, pp.747-778.
21.
Greenhoot JH and Reichenbach DD (1969). Cardiac injury and sub-arachnoid hemorrhage. A clinical, pathological, and physiological correlation. J. Neurosurg. 30: 521-531.
22.
Gupta RC, McLean MJ, and Dettbarn WD (1987). Prophylaxis and treatment against the toxicity of organophosphate (op) compounds in rat by memantine and atropine. Toxicologist7: 276.
23.
Hawkins WE and Clower BR (1971). Myocardial damage after head trauma and simulated intracranial hemorrhage in mice: The role of the autonomic nervous system . Cardiovasc. Res. 5: 524-529.
24.
Hayward IJ, Wall HG, Jaax NK, Wade JV, Marlow DD, and Nold JB (1990). Decreased brain pathology in organophosphate-exposed rhesus monkeys following benzodiazepine therapy. J. Neurol. Sci. 98: 99-106.
25.
Juhasz-Nagy A., Szentivanyi M., Ovary I., and Debreczeni L. (1965). Hypothalamic control of coronary circulation in the dog. Arch. Int. Physiol. Biochem. 73: 798-816.
26.
Junqueira LC and Carneiro J. (1971). Basic Histology . LANGE Medical Publications, Los Altos, California.
27.
Kadar T., Cohen G., Sahar R., Alkalai D., and Shapira S. (1992). Long-term study of brain lesions following soman, in comparison to DFP and metrazol poisoning. Hum. Exp. Toxicol . 11: 517-523.
28.
King JM, Roth L., and Haschek WM (1982). Myocardial necrosis secondary to neural lesions in domestic animals. J. Am. Vet. Med. Assoc. 180: 144-148.
29.
Klouda MA and Brynjolfsson G. (1969). Cardiotoxic effects of electrical stimulation of the stellate ganglia. Ann. N.Y. Acad. Sci. 156: 271-280.
30.
Lallement G. , Carpentier P., Collet A., Baubichon D., Pernotmarino I., and Blanchet G. (1992). Extracellular acetylcholine changes in rat limbic structures during soman-induced seizures. NeuroToxicology13: 557-567.
31.
Lallement G. , Delamanche IS, Pernotmarino I., Baubichon D., Denoyer M., Carpentier P., and Blanchet G. (1993). Neuroprotective activity of glutamate receptor antagonists against soman-induced hippocampal damage-Quantification with an omega-3 site ligand . Brain Res. 618: 227-237.
32.
Lallement G. , Denoyer M., Collet A., Pernotmarino I., Baubichon D., Monmaur P., and Blanchet G. (1992). Changes in hippocampal acetylcholine and glutamate extracellular levels during soman-induced seizures-Influence of septal cholinoceptive cells. Neurosci. Lett. 139: 104-107.
33.
Lemercier G. , Carpentier P., Sentenac-Roumanou H., and Morelis P. (1983). Histological and histochemical changes in the central nervous system of the rat poisoned by an irreversible anticholinesterase organophosphorus compound . Acta Neuropathol.(Berlin) 61: 123-129.
34.
Lipp JA (1968). Cerebral electrical activity following soman administration . Arch. Int. Pharmacodyn. Ther. 175: 161-169.
35.
McDonough JH , Hackley BE, Cross R., Samson F., and Nelson S. (1983). Brain regional glucose use during soman-induced seizures. NeuroToxicology4: 203-210.
36.
McDonough JH , Jaax NK, Crowley RA, Mays MZ, and Modrow HE (1989). Atropine and/or diazepam therapy protects against soman-induced neural and cardiac pathology. Fund. Appl. Toxicol. 13: 256-276.
37.
McDonough JH , McLeod CG, and Nipwoda MT (1987). Direct microinjection of soman or vx into the amygdala produces repetitive limbic convulsions and neuropathology. Brain Res. 435: 123-137.
38.
McLeod CG (1985). Pathology of nerve agents: Perspectives on medical management. Fund. Appl. Toxicol. 5: s10-s16.
39.
McLeod CG, Singer AW, and Harrington DG (1984). Acute neuropathology in soman poisoned rats. NeuroToxicology5: 53-58.
40.
McNair JL, Clower BR, and Sandford RA (1970). The effect of reserpine pretreatment on myocardial damage associated with simulated intracranial hemorrhage in mice. Eur. J. Pharmacol . 9: 1-6.
41.
Moreva E. (1980). Methods for producing experimental neurogenic lesions. In: Neurogenic Heart Lesions, IS ZavodskayaEV Moreva , and NA Novikova (eds). Pergamon Press, Oxford, pp. 9-22.
42.
Oppenheimer S. (1992). The insular cortex and the pathophysiology of stroke-induced cardiac changes. Can. J. Neurol. Sci. 19: 208- 211.
43.
Pazdernik TL , Cross R., Giesler M., Samson F., and Nelson S. (1985). Changes in local cerebral glucose utilization induced by convulsants . Neuroscience14: 823-835.
44.
Rockhold R. (1991). Cardiotoxicity of naturally occurring catecholamines . In: Principles of Cardiac Toxicology , SI Baskin (ed). CRC Press, Boca Raton, Florida pp. 347-417.
45.
Rodwell VW, Murray RK, and Keeley FW (1990). Contractile and structural proteins. In: Harper's Biochemistry, RK Murray , DK Granner, PA Mayes , and VW Rodwell (eds). Appleton and Lange, San Mateo, California , pp. 627-644.
46.
Rona G., Huttner I., and Boutet M. (1977). Microcirculatory changes in myocardium with particular reference to catecholamine-induced cardiac muscle cell injury. In: Handbuch der Allgemeinen Pathologie, Vol. III, H Meesen (ed). Springer-Verlag , Berlin, pp. 791- 888.
47.
Roth A., Zellinger I., Arad M., and Atsmon J. (1993). Organophosphates and the heart. Chest103: 576-582.
48.
Schenk EA and Moss AJ (1966). Cardiovascular effects of sustained norepinephrine infusions. II Morphology. Circulation Res. 18: 605-615.
49.
Shih TM (1982). Time course effects of soman on acetylcholine and choline levels in six discrete areas of the rat brain. Psychopharmacology78: 170-175.
50.
Shih TM, Penetar DM, Mcdonough JH, Romano JA, and King JM (1990). Age-related differences in soman toxicity and in blood and brain regional cholinesterase activity. Brain Res. Bull. 24: 429-436.
51.
Singal PK, Dhillon KS, Beamish RE, and Dhalla NS (1981). Protective effect of zinc against catecholamine-induced myocardial changes: Electrocardiographic and ultrastructure studies. Lab. Invest. 44: 426-433.
52.
Singal PK, Kapur N., Dhillon KS, Beamish RE, and Dhalla NS (1982). Role of free radicals in catecholamine-induced cardiomyopathy. Can. J. Physiol. Pharmacol. 60: 1390-1397.
53.
Singal PK, Panagia V., Beamish RE, and Dhalla NS (1985). Role of calcium in heart function in health and disease. In: Calcium in Biological Systems, RP Rubin, GB Weiss , and JW Putney (eds). Plenum Press, New York, pp. 361-368.
54.
Singer AW, Jaax NK, Graham JS, and McLeod CG (1987). Cardiomyopathy in soman and sarin intoxicated rats. Toxicol Lett. 36: 243-249.
55.
Tower D. (1988). Development of the knowledge of atrocytes since Virchow. In: Biochemical Pathology of Astrocytes, MD Norenberg, L Hertz , and A Schousboe (eds). Alan R. Liss, New York, pp. 3-18.
56.
Tryphonas L. and Clement JG (1993). Dose and time related effects on the CNS and heart of rats exposed to a single dose of soman: A histopathological study. U.S. Army 1993 Med. Def. Biosci. Rev. May 10-13, Baltimore, Maryland, pp. 685-694.
57.
Tryphonas L. and Clement JG (1995). Histomorphogenesis of soman-induced encephalocardiomyopathy in Sprague-Dawley rats. Toxicol. Pathol. 23: 393-409.
58.
Weilder DJ (1974). Myocardial damage and cardiac arrhythmias after intracranial hemorrhage. A critical review. Stroke20: 133- 183.
