Abstract
During most infections plasma, concentrations of trace elements change, but it is unclear if this reflects changes in infected target tissues. In coxsackievirus B3 (CB3) infection, the myocardium is a target in both humans and mice. The concentrations of 12 trace elements were analyzed by inductively coupled plasma-mass spectrometry (ICP-MS) in the myocardium of sham-inoculated controls and infected A/J mice 4 and 7 d postinoculation. The size of the inflammatory lesion was positively correlated to the virus content of the heart, as estimated by histopathology and in situ hybridization, respectively. Iron, cobalt, vanadium, and selenium showed transient changes, whereas for the other elements, tendencies on d 4 were manifest on d 7. A threefold increase in calcium on d 7 suggests prestages of calcification, whereas increases in zinc, selenium, and copper may be the result of the accumulation of immune cells. The magnesium decrease may contribute to the increased sensitivity to cardiac arrhythmias in myocarditis.
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References
W. R. Beisel, R. S. Pekarek, and R. W. Wannemacher, Jr., The impact of infectious diseases on trace element metabolism in the host, in Trace Element Metabolism in Animals, G. Hoekstra, H. E. Gauther, and W. Mertz, eds., University Park Press, Baltimore, pp. 217–240 (1974).
W. R. Beisel, Metabolic response of the host to infections, in Textbook of Pediatric Infectious Disease, 2nd ed., R. D. Feigin and J. D. Cherry, eds., W. B. Saunders, Philadelphia, pp. 54–69 (1998).
G. Friman and N.-G. Ilbäck, Acute infection: metabolic responses, effects on performance, interaction with exercise, and myocarditis, Int. J. Sports Med. 19, S1-S11 (1998).
F. O. Brady, Induction of metallothionein in rats, in Methods in Enzymology: Metallobiochemistry of MT and Related Molecules, Vol. 205, J. F. Riordan and B. L. Vallee, eds., Academic Press, San Diego, CA, pp. 559–567 (1991).
M. P. Waalkes and P. L. Goering, Metallothionein and other cadmium-binding proteins: recent developments, Chem. Res. Toxicol. 3, 281–288 (1990).
P. Z. Sobocinski, W. J. Canterbury, C. A. Mapes, and R. E. Dinterman, Involvement of hepatic metallothioneins in hypozincemia associated with bacterial infection, Am. J. Physiol. 234, E399-E406 (1978).
A. H. Shankar and A. S. Prasad, Zinc and immune function: the biological basis of altered resistance to infection, Am. J. Clin. Nutr. 68, S447-S463 (1998).
A. Frank, V. Galgan, A. Roos, M. Olsson, L. R. Petersson, and A. Bignert, Metal concentration in seals from Swedish waters, AMBIO 21, 529–538 (1992).
N.-G. Ilbäck, U. Lindh, J. Fohlman, and G. Friman, New aspects from murine coxsackie B3 myocarditis—focus on heavy metals, Eur. Heart J. 16, 20–24 (1995).
N.-G. Ilbäck, J. Fohlman, and G. Friman, The protective effect of selenium on the development of coxsackievirus B3 induced inflammatory lesions in the murine myocardium, J. Trace Element Exp. Med. 2, 257–266 (1989).
M. A. Beck and O. A. Levander, Dietary oxidative stress and the potentiation of viral infection, Annu. Rev. Nutr. 18, 93–116 (1998).
M. Merza, E. Larsson, M. Steen, and B. Morein, Association of a retrovirus with a wasting condition in the Swedish moose, Virology 202, 956–961 (1994).
A. Frank, V. Galgan, and L. R. Petersson, Secondary copper deficiency, chromium deficiency and trace element imbalance in the moose (Alces alces L.): effect of anthropogenic activity, AMBIO 23, 315–317 (1994).
V. Galgan and A. Frank, Survey of bioavailable selenium in Sweden with the moose (Alces alces L.) as monitoring animal, Sci. Total Environ. 172, 37–45 (1995).
J. F. Woodruff, Viral myocarditis. A review, Am. J. Pathol. 101, 424–479 (1980).
S. A. Huber, Animal models: immunological aspects, in Viral Infections of the Heart, J. E. Banatvala, ed., Hodder and Stoughton, London, pp. 82–109 (1993).
E. K. Godeny and C. J. Gauntt, Murine natural killer cells limit coxsackievirus B3 replication, J. Immunol. 139, 913–918 (1987).
A. Henke, S. Huber, A. Stelzner, and J. L. Whitton, The role of CD8+ T lymphocytes in coxsackievirus B3-induced myocarditis, J. Virol. 69, 6720–6728 (1995).
Y. Seko, Y. Shinkai, A. Kawasaki, H. Yagita, K. Okumura, F. Takaku, et al., Expression of perforin in infiltrating cells in murine hearts with acute myocarditis caused by coxsackievirus B3, Circulation 84, 788–795 (1991).
A. Stallion, J. F. Rafferty, B. W. Warner, M. M. Ziegler, and F. C. Ryckman, Myocardial calcification: a predictor of poor outcome for myocarditis treated with extracorporeal life support, J. Pediatr. Surg. 29, 492–494 (1994).
L. H. Chow, C. J. Gauntt, and B. M. McManus, Differential effects of myocarditic variants of Coxsackievirus B3 in inbred mice—a pathologic characterization of heart tissue damage, Lab. Invest. 64, 55–64 (1991).
J. F. Woodruff and E. D. Kilbourne, The influence of quantitated post weaning undernutrition in coxsackievirus B3-infection of adult mice. I. Viral persistence and increased severity of lesions, J. Infect. Dis. 121, 137–163 (1970).
P. O. K. Stålhandske, M. Lindberg, and U. Petterson, Genome of coxsackievirus B3, Virology 156, 50–63 (1987).
M. Kallajoki, H. Kalimo, L. Wesslén, P. Auvinen, and T. Hyypiä, In situ detection of enterovirus genomes in mouse myocardial tissue by ribonucleic acid probes, Lab. Invest. 63, 669–675 (1990).
G. Friman, N.-G. Ilbäck, and W. R. Beisel, The effect of strenuous exercise on infection with Franciscella tularensis in rats, J. Infect. Dis. 145, 706–714 (1982).
N.-G. Ilbäck, G. Friman, R. L. Squibb, A. J. Johnson, D. A. Balentine, and W. R. Beisel, The effect of exercise and fasting on the myocardial protein and lipid metabolism in experimental bacterial myocarditis, Acta Pathol. Microbiol. Immunol. Scand. 92, 195–204 (1984).
B. M. Altura and B. T. Altura, Cardiovascular risk factors and magnesium: relationships to atherosclerosis, ischemic heart disease and hypertension, Magnes. Trace Element 10, 182–192 (1991).
G. Bo-Qi, Pathology of Keshan disease—a comprehensive review, Chin. Med. J. 96, 251–261 (1983).
M. A. Beck, P. C. Kolbeck, Q. Shi, C. V. Morris, and O. A. Levander, Increased virulence of a human enterovirus (coxsackievirus B3) in selenium-deficient mice, J. Infect. Dis. 170, 351–357 (1994).
L. Kiremidjian, M. Roy, H. I. Wishe, M. W. Cohen, and G. Stotzky, Supplementation with selenium augments the functions of natural killer and lymphokine-activated killer cells, Biol. Trace Element Res. 52, 227–239 (1996).
N.-G. Ilbäck, J. Fohlman, and G. Friman, Effects of selenium supplementation on virus-induced inflammatory heart disease, Biol. Trace Element Res. 63, 51–66 (1998).
E. D. Savlov, W. H. Strain, and F. Heugin, Radio zinc studies in experimental wound healing, J. Surg. Res. 2, 209–212 (1962).
S. Cunningham-Rundles, Zinc modulation of immune function: specificity and mechanism of interaction, J. Lab. Clin. Med. 128, 9–11 (1991).
P. J. Fraker, P. DePasquale-Jardieu, C. M. Zwickl, and R. W. Luecke, Regeneration of T-helper cell functions in zinc deficient adult mice, Proc. Natl. Acad. Sci. 75, 5660–5664 (1978).
L. Tapazoglou, A. S. Prasad, G. Hill, G. F. Brewer, and J. Kaplan, Decreased natural killer cell activity in patients with zinc deficiency with sickle cell disease, J. Lab. Clin. Med. 105, 19–22 (1985).
S. S. Percival, Copper and immunity, Am. J. Clin. Nutr. 67, S1064-S1068 (1998).
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Funseth, E., Lindh, U., Wesslén, L. et al. Trace element changes in the myocardium during coxsackievirus B3 myocarditis in the mouse. Biol Trace Elem Res 76, 149–160 (2000). https://doi.org/10.1385/BTER:76:2:149
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DOI: https://doi.org/10.1385/BTER:76:2:149