Abstract
Large doses of monensin, a Na+-selective carboxylic ionophore, produce polyfocal, monophasic necrosis of skeletal muscle, with Type I fiber selectivity, in swine. For a study of the sequential ultrastructural alterations in affected skeletal muscles, 14 weanling pigs were given 40 mg monensin/kg body weight and were euthanatized 1, 2, 4, 8, and 16 days later. Myotoxicosis and myoglobinuria were apparent clinically. At necropsy, white, dry areas of necrosis were present in the muscle masses of the anterior and posterior thigh, shoulder, and loin. Two patterns of skeletal muscle necrosis were observed on Day 1, especially in Type I fibers. In fibers exhibiting the first of these patterns, the contractile material was disrupted, forming dense amorphous and filamentous clumps scattered within the persistent sheaths of external lamina (sarcolemmal tubes); the mitochondria were swollen and contained flocculent matrix densities, and the nuclei were pyknotic. Fibers showing the second pattern were uniformly dense, but their sarcoplasm was not disrupted. Sublethally injured fibers were also observed and showed focal myofibrillar lysis. On Days 2 and 4, the necrotic muscle had marked infiltration of macrophages in the interstitium and within sarcolemmal tubes. Rapid resolution of the fiber necrosis occurred by phagocytosis of the sarcoplasmic debris. Regeneration of affected muscles developed early following injury and progressed rapidly to complete restoration of the necrotic muscles without residual fibrosis. Regeneration was initiated on Day 1 by activation of satellite cells to form presumptive myoblasts; on Days 4 and 8 these cells showed evidence of fusion, forming myotubes to restore the necrotic fibers.
Full text
PDF










Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bassett A. L., Wiggins J. R., Gelband H., Pressman B. C. Monensin potentiation of potassium contracture in cat myocardium. J Pharmacol Exp Ther. 1978 Dec;207(3):966–975. [PubMed] [Google Scholar]
- Benoit P. W., Belt W. D. Destruction and regeneration of skeletal muscle after treatment with a local anaesthetic, bupivacaine (Marcaine). J Anat. 1970 Nov;107(Pt 3):547–556. [PMC free article] [PubMed] [Google Scholar]
- Cantin M. Skeletal muscle lesions in iodide-treated rats. Arch Pathol. 1967 Jun;83(6):500–506. [PubMed] [Google Scholar]
- Clarke J. T., Karpati G., Carpenter S., Wolfe L. S. The effect of vincristine on skeletal muscle in the rat. A correlative histochemical, ultrastructural and chemical study. J Neuropathol Exp Neurol. 1972 Apr;31(2):247–266. doi: 10.1097/00005072-197204000-00003. [DOI] [PubMed] [Google Scholar]
- Cogen F. C., Rigg G., Simmons J. L., Domino E. F. Phencyclidine-associated acute rhabdomyolysis. Ann Intern Med. 1978 Feb;88(2):210–212. doi: 10.7326/0003-4819-88-2-210. [DOI] [PubMed] [Google Scholar]
- Collins E. A., McCrea C. T. Monensin sodium toxicity in cattle. Vet Rec. 1978 Oct 21;103(17):386–386. doi: 10.1136/vr.103.17.386. [DOI] [PubMed] [Google Scholar]
- Cullen M. J., Appleyard S. T., Bindoff L. Morphologic aspects of muscle breakdown and lysosomal activation. Ann N Y Acad Sci. 1979;317:440–464. [PubMed] [Google Scholar]
- D AGOSTINO A. N. AN ELECTRON MICROSCOPIC STUDY OF SKELETAL AND CARDIAC MUSCLE OF THE RAT POISONED BY PLASMOCID. Lab Invest. 1963 Nov;12:1060–1071. [PubMed] [Google Scholar]
- DEWAN M. L., HENSON J. B., DOLLAHITE J. W., BRIDGES C. H. TOXIC MYODEGENERATION IN GOATS PRODUCED BY FEEDING MATURE FRUITS FROM THE COYOTILLO PLANT (KARWINSKIA HUMBOLDTIANA). Am J Pathol. 1965 Feb;46:215–226. [PMC free article] [PubMed] [Google Scholar]
- Donev B., Stoianov K., Dzhurov A., Dilov P. Ostra i subkhronichna toksichnost na monenzina za agneta. Vet Med Nauki. 1980;17(1):17–25. [PubMed] [Google Scholar]
- Drake J. N. Monensin-tiamulin interaction risk to pigs. Vet Rec. 1981 Mar 7;108(10):219–220. doi: 10.1136/vr.108.10.219. [DOI] [PubMed] [Google Scholar]
- Duane D. D., Engel A. G. Emetine myopathy. Neurology. 1970 Aug;20(8):733–739. doi: 10.1212/wnl.20.8.733. [DOI] [PubMed] [Google Scholar]
- Duncan C. J., Smith J. L., Greenaway H. C. Failure to protect frog skeletal muscle from ionophore-induced damage by the use of the protease inhibitor leupeptin. Comp Biochem Physiol C. 1979;63C(1):205–207. doi: 10.1016/0306-4492(79)90149-7. [DOI] [PubMed] [Google Scholar]
- Duncan C. J., Smith J. L. The action of caffeine in promoting ultrastructural damage in frog skeletal muscle fibres. Evidence for the involvement of the calcium-induced release of calcium from the sarcoplasmic reticulum. Naunyn Schmiedebergs Arch Pharmacol. 1978 Nov;305(2):159–166. doi: 10.1007/BF00508287. [DOI] [PubMed] [Google Scholar]
- Eadie M. J., Ferrier T. M. Chloroquine myopathy. J Neurol Neurosurg Psychiatry. 1966 Aug;29(4):331–337. doi: 10.1136/jnnp.29.4.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Giusti G. V., Chiarotti M., Passatore M., Gentile V., Fiori A. Muscular dystrophy in mice after chronic subcutaneous treatment with cannabinoids. Forensic Sci. 1977 Sep-Oct;10(2):133–140. doi: 10.1016/0300-9432(77)90106-6. [DOI] [PubMed] [Google Scholar]
- Gleiser C. A., Bay W. W., Dukes T. W., Brown R. S., Read W. K., Pierce K. R. Study of chloroquine toxicity and a drug-induced cerebrospinal lipodystrophy in swine. Am J Pathol. 1968 Jul;53(1):27–45. [PMC free article] [PubMed] [Google Scholar]
- Grasso P., Muir A., Golberg L., Batstone E. Studies on Brown FK. IV. Cytopathic effects of Brown FK on cardiac and skeletal muscle in the rat. Food Cosmet Toxicol. 1968 Jun;6(1):13–24. doi: 10.1016/0015-6264(68)90076-x. [DOI] [PubMed] [Google Scholar]
- Griffing W. J., Todd G. C., Pierce E. C. Ultrastructural changes in rat skeletal and cardiac muscle induced by A204. Antimicrob Agents Chemother (Bethesda) 1970;10:366–373. [PubMed] [Google Scholar]
- Grueter H. P., Elliston N. G., McAskill J. W., Potter E. L. Effect of Rumensin on feed efficiency of cattle. Vet Med Small Anim Clin. 1976 Feb;71(2):198–200. [PubMed] [Google Scholar]
- Haney M. E., Jr, Hoehn M. M. Monensin, a new biologically active compound. I. Discovery and isolation. Antimicrob Agents Chemother (Bethesda) 1967;7:349–352. doi: 10.1128/AAC.7.3.349. [DOI] [PubMed] [Google Scholar]
- Hanrahan L. A., Corrier D. E., Nagi S. A. Monensin toxicosis in broiler chickens. Vet Pathol. 1981 Sep;18(5):665–671. doi: 10.1177/030098588101800511. [DOI] [PubMed] [Google Scholar]
- Henson J. B., Dollahite J. W. Toxic myodegeneration in calves produced by experimental Cassia occidentalis intoxication. Am J Vet Res. 1966 Jul;27(119):947–949. [PubMed] [Google Scholar]
- Horrox N. E. Monensin-tiamulin interaction risk to poultry. Vet Rec. 1980 Mar 22;106(12):278–278. doi: 10.1136/vr.106.12.278. [DOI] [PubMed] [Google Scholar]
- Howell J., Hanson J., Onderka D., Harries W. N. Monensin toxicity in chickens. Avian Dis. 1980 Oct-Dec;24(4):1050–1053. [PubMed] [Google Scholar]
- Hughes J. T., Esiri M., Oxbury J. M., Whitty C. W. Chloroquine myopathy. Q J Med. 1971 Jan;40(157):85–93. [PubMed] [Google Scholar]
- JASMIN G., GAREAU R. Histopathological study of muscle lesions produced by paraphenylenediamine in rats. Br J Exp Pathol. 1961 Dec;42:592–596. [PMC free article] [PubMed] [Google Scholar]
- Janzen E. D., Rodostits O. M., Orr J. P. Possible monensin poisoning in a group of bulls. Can Vet J. 1981 Apr;22(4):92–94. [PMC free article] [PubMed] [Google Scholar]
- Jirmanová I., Thesleff S. Ultrastructural study of experimental muscle degeneration and regeneration in the adult rat. Z Zellforsch Mikrosk Anat. 1972;131(1):77–97. doi: 10.1007/BF00307202. [DOI] [PubMed] [Google Scholar]
- Kemp J. Monensin poisoning in turkeys. Vet Rec. 1978 May 27;102(21):467–467. doi: 10.1136/vr.102.21.467. [DOI] [PubMed] [Google Scholar]
- Lane R. J., McLelland N. J., Martin A. M., Mastaglia F. L. Epsilon aminocaproic acid (EACA) myopathy. Postgrad Med J. 1979;55(642):282–285. doi: 10.1136/pgmj.55.642.282. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Macdonald R. D., Engel A. G. Experimental chloroquine myopathy. J Neuropathol Exp Neurol. 1970 Jul;29(3):479–499. doi: 10.1097/00005072-197007000-00010. [DOI] [PubMed] [Google Scholar]
- Mascrès C., Jasmin G. Altérations de la fibre musculaire induites chez le rat par la p-phénylénediamine. Pathol Biol (Paris) 1975 Mar;23(3):193–199. [PubMed] [Google Scholar]
- Matsuoka T. Evaluation of monensin toxicity in the horse. J Am Vet Med Assoc. 1976 Nov 15;169(10):1098–1100. [PubMed] [Google Scholar]
- Mercer H. D., Neal F. C., Himes J. A., Edds G. T. Cassia occidentalis toxicosis in cattle. J Am Vet Med Assoc. 1967 Sep 15;151(6):735–741. [PubMed] [Google Scholar]
- Mollenhauer H. H., Rowe L. D., Cysewski S. J., Witzel D. A. Ultrastructural observations in ponies after treatment with monensin. Am J Vet Res. 1981 Jan;42(1):35–40. [PubMed] [Google Scholar]
- Muir A. R. Normal and regenerating skeletal muscle fibres in Pietrain pigs. J Comp Pathol. 1970 Jan;80(1):137–143. doi: 10.1016/0021-9975(70)90040-x. [DOI] [PubMed] [Google Scholar]
- Muylle E., Vandenhende C., Oyaert W., Thoonen H., Vlaeminck K. Delayed monensin sodium toxicity in horses. Equine Vet J. 1981 Apr;13(2):107–108. doi: 10.1111/j.2042-3306.1981.tb04129.x. [DOI] [PubMed] [Google Scholar]
- Nation P. N., Crowe S. P., Harries W. N. Clinical signs and pathology of accidental monensin poisoning in sheep. Can Vet J. 1982 Nov;23(11):323–326. [PMC free article] [PubMed] [Google Scholar]
- O'Hara P. J., Pierce K. R., Read W. K. Degenerative myopathy associated with ingestion of Cassia occidentalis L.: clinical and pathologic features of the experimentally induced disease. Am J Vet Res. 1969 Dec;30(12):2173–2180. [PubMed] [Google Scholar]
- Oberc M. A., Engel W. K. Ultrastructural localization of calcium in normal and abnormal skeletal muscle. Lab Invest. 1977 Jun;36(6):566–577. [PubMed] [Google Scholar]
- Ordidge R. M., Schubert F. K., Stoker J. W. Death of horses after accidental feeding of monensin. Vet Rec. 1979 Apr 21;104(16):375–375. doi: 10.1136/vr.104.16.375. [DOI] [PubMed] [Google Scholar]
- PRICE H., PEASE D. C., PEARSON C. M. Selective actin filament and Z-band degeneration induced by plasmocid. An electron microscopic study. Lab Invest. 1962 Jul;11:549–562. [PubMed] [Google Scholar]
- Pott J. M., Shov B. Monensin--tiamulin interactions in pigs. Vet Rec. 1981 Dec 12;109(24):545–545. [PubMed] [Google Scholar]
- Pott J. M., Shov B. Monensin--tiamulin interactions in pigs. Vet Rec. 1981 Dec 12;109(24):545–545. [PubMed] [Google Scholar]
- Pressman B. C. Biological applications of ionophores. Annu Rev Biochem. 1976;45:501–530. doi: 10.1146/annurev.bi.45.070176.002441. [DOI] [PubMed] [Google Scholar]
- Pressman B. C. Properties of ionophores with broad range cation selectivity. Fed Proc. 1973 Jun;32(6):1698–1703. [PubMed] [Google Scholar]
- Publicover S. J., Duncan C. J., Smith J. L. The use of A23187 to demonstrate the role of intracellular calcium in causing ultrastructural damage in mammalian muscle. J Neuropathol Exp Neurol. 1978 Sep;37(5):554–557. [PubMed] [Google Scholar]
- Reznik M. Origin of myoblasts during skeletal muscle regeneration. Electron microscopic observations. Lab Invest. 1969 Apr;20(4):353–363. [PubMed] [Google Scholar]
- Ruth G. R., Van Vleet J. F. Experimentally induced selenium-vitamin E deficiency in growing swine: selective destruction type I skeletal muscle fibers. Am J Vet Res. 1974 Feb;35(2):237–244. [PubMed] [Google Scholar]
- SMITH H. A. The pathology of gossypol poisoning. Am J Pathol. 1957 Mar-Apr;33(2):353–365. [PMC free article] [PubMed] [Google Scholar]
- Schmalbruch H. The morphology of regeneration of skeletal muscles in the rat. Tissue Cell. 1976;8(4):673–692. doi: 10.1016/0040-8166(76)90039-2. [DOI] [PubMed] [Google Scholar]
- Smith B., O'Grady F. Experimental chloroquine myopathy. J Neurol Neurosurg Psychiatry. 1966 Jun;29(3):255–258. doi: 10.1136/jnnp.29.3.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Statham H. E., Duncan C. J., Smith J. L. The effect of the ionophore A23187 on the ultrastructure and electrophysiological properties of frog skeletal muscle. Cell Tissue Res. 1976 Oct 6;173(2):193–209. doi: 10.1007/BF00221375. [DOI] [PubMed] [Google Scholar]
- Stuart J. C. An outbreak of monensin poisoning in adult turkeys. Vet Rec. 1978 Apr 8;102(14):303–304. doi: 10.1136/vr.102.14.303. [DOI] [PubMed] [Google Scholar]
- Sutko J. L., Besch H. R., Jr, Bailey J. C., Zimmerman G., Watanabe A. M. Direct effects of the monovalent cation ionophores monensin and nigericin on myocardium. J Pharmacol Exp Ther. 1977 Dec;203(3):685–700. [PubMed] [Google Scholar]
- Tannenberg J. Pathological changes in the heart, skeletal musculature and liver in rabbits treated with insulin in shock dosage. Am J Pathol. 1939 Jan;15(1):25–54.11. [PMC free article] [PubMed] [Google Scholar]
- Teräväinen H., Larsen A., Hillbom M. Clofibrate-induced myopathy in the rat. Acta Neuropathol. 1977 Aug 16;39(2):135–138. doi: 10.1007/BF00703319. [DOI] [PubMed] [Google Scholar]
- Todd G. C., Meyers D. B., Pierce E. C., Worth H. M. Acute reversible myopathy produced by compound A204. Antimicrob Agents Chemother (Bethesda) 1970;10:361–365. [PubMed] [Google Scholar]
- Trump B. F., Berezesky I. K., Laiho K. U., Osornio A. R., Mergner W. J., Smith M. W. The role of calcium in cell injury. A review. Scan Electron Microsc. 1980;(Pt 2):437-62, 492. [PubMed] [Google Scholar]
- Van Vleet J. F., Amstutz H. E., Weirich W. E., Rebar A. H., Ferrans V. J. Acute monensin toxicosis in swine: effect of graded doses of monensin and protection of swine by pretreatment with selenium-vitamin E. Am J Vet Res. 1983 Aug;44(8):1460–1468. [PubMed] [Google Scholar]
- Van Vleet J. F., Amstutz H. E., Weirich W. E., Rebar A. H., Ferrans V. J. Clinical, clinicopathologic, and pathologic alterations in acute monensin toxicosis in cattle. Am J Vet Res. 1983 Nov;44(11):2133–2144. [PubMed] [Google Scholar]
- Van Vleet J. F., Amstutz H. E., Weirich W. E., Rebar A. H., Ferrans V. J. Clinical, clinicopathologic, and pathologic alterations of monensin toxicosis in swine. Am J Vet Res. 1983 Aug;44(8):1469–1475. [PubMed] [Google Scholar]
- Van Vleet J. F., Ferrans V. J. Ultrastructural alterations in the atrial myocardium of pigs with acute monensin toxicosis. Am J Pathol. 1984 Mar;114(3):367–379. [PMC free article] [PubMed] [Google Scholar]
- Van Vleet J. F., Ferrans V. J. Ultrastructural changes in skeletal muscle of selenium-vitamin E-deficient chicks. Am J Vet Res. 1976 Sep;37(9):1081–1089. [PubMed] [Google Scholar]
- Van Vleet J. F., Ferrans V. J. Ultrastructural myocardial alterations in monensin toxicosis of cattle. Am J Vet Res. 1983 Sep;44(9):1629–1636. [PubMed] [Google Scholar]
- Van Vleet J. F., Meyer K. B., Olander H. J. Acute selenium toxicosis induced in baby pigs by parenteral administration of selenium-vitamin E preparations. J Am Vet Med Assoc. 1974 Sep 15;165(6):543–547. [PubMed] [Google Scholar]
- Walters M. N., Papadimitriou J. M., Shilkin K. B. Inflammation induced by dimethylsulfoxide (DMSO). 1. Ultrastructural investigation of preinflammatory phase. Exp Mol Pathol. 1967 Feb;6(1):106–117. doi: 10.1016/0014-4800(67)90009-3. [DOI] [PubMed] [Google Scholar]
- Wentink G. H., Vente J. P. Een geval van monensin-vergiftiging bij melkvee. Tijdschr Diergeneeskd. 1981 Jun 15;106(12):623–625. [PubMed] [Google Scholar]
- Wilson J. S. Toxic myopathy in a dog associated with the presence of monensin in dry food. Can Vet J. 1980 Jan;21(1):30–31. [PMC free article] [PubMed] [Google Scholar]
- Worth H. M., Meyers D. B., Gibson W. R., Todd G. C. Acute and subacute toxicity of A204. Antimicrob Agents Chemother (Bethesda) 1970;10:357–360. [PubMed] [Google Scholar]
- Wrogemann K., Pena S. D. Mitochondrial calcium overload: A general mechanism for cell-necrosis in muscle diseases. Lancet. 1976 Mar 27;1(7961):672–674. doi: 10.1016/s0140-6736(76)92781-1. [DOI] [PubMed] [Google Scholar]










