Summary
The adaptation of normal and splenectomized mice to increasing concentrations of carbon monoxide (CO) in air, and their subsequent long-term survival in it were studied. From the 10th day onwards the concentration of CO was maintained at 0.24%, which produced a carboxyhaemoglobin level of about 74% in the blood, and which was normally lethal within 24 h. However, the non-splenectomized mice survived in this environment for an average of 47 days, but splenectomized mice survived for 101 days.
During adaptation to CO there were marked increases in the haematocrit level and the concentration of haemoglobin, a massive release of reticulocytes into the circulation, and increases in blood volume, spleen and heart weight. However, changes in the above haematological parameters were significantly less in splenectomized than in normal animals. These differences were attributed to the loss of the erythropoietic reserves of the spleen.
In splenectomized mice which survived for over 90 days in CO there was histological evidence for the development of extramedullary erythropoiesis, as well as increased erythropoietic activity in the marrow of the tail vertebrae, which occurred earlier. Deaths were most frequently associated with massive internal haemorrhages in both groups of animals. This is discussed in relation to histological and haematological findings. Also in both groups, there was evidence that both hypertrophy and hyperplasia of heart muscle fibres occurred during adaptation to breathing CO.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abidin, B. I., Kustov, V. V., Belkin, V. I., Poddubnaya, L. T.: Effect of a continuous and intermittent exposure of animals to carbon monoxide. Kosm. Biol. [Russian] 7, 17–21 (1973)
Adams, J. D., Erickson, H. H., Stone, H. L.: Myocardial metabolism during exposure to carbon monoxide in the conscious dog. J. appl. Physiol. 34, 238–242 (1973)
Aggio, M. C.: Studies on the functional capacity of the erythropoietic bone marrow in the mouse. Acta physiol. latinoamer. 23, 535–537 (1973)
Aggio, M. C., García, N. E.: Efecto de la esplenectomía sobre la eritropoyesis en el ratón. Revta esp. Fisiol. 25, 239–244 (1969)
Anderson, E. W., Andelman, R. J., Strauch, J. U., Fortuin, N. J., Knelson, J. H.: Effect of low level carbon monoxide exposure on onset and duration of angina pectoris. A study in ten patients with ischaemic heart disease. Ann. intern. Med. 79, 46–50 (1973)
Aschoff, L.: Pathologische Anatomie. Bd. 2, 8 Aufl., S. 37. Berlin: Fischer 1936
Astrup, P.: Some physiological and pathological effects of moderate carbon monoxide exposure. Brit. med. J. 1972a 4, 447–452
Astrup, P.: Carbon monoxide in tobacco smoke and its influence on the development of vascular diseases. Rehabilitation (Bonn) 25, 11–12 (1972b)
Ayres, S. M., Giannelli, S., Jr., Mueller, H.: Myocardial and systemic responses to carboxyhemoglobin. Ann. N.Y. Acad. Sci. 174, 268–293 (1970)
Baker, G. M.: Personal communication (1974)
DeBias, D. A., Banerjee, C. M., Birkhead, N. C., Harrer, W. V., Kazal, L. A.: Carbon monoxide inhalation effects following myocardial infarction in monkeys. Arch. environm. Hlth 27. 161–167 (1973)
Bozzini, C. E., Barrio Rendo, M. E., Devoto, F. C. H., Epper, C. E.: Studies on medullary and extramedullary erythropoiesis in the adult mouse. Amer. J. Physiol. 219, 724–728 (1970)
Campbell, J. A.: Hypertrophy of the heart in acclimatization to chronic carbon monoxide poisoning. J. Physiol. (Lond.) 77, 8P-9P (1933)
Eckardt, R. E., MacFarland, H. N., Alarie, Y. V. E., Busey, W. M.: The biologic effect from long-term exposure of primates to carbon monoxide. Arch. environm. Hlth 25, 381–387 (1972)
Kastner, M. R. Q. de, Cardeman, L.: Hematopoietic involvement of the spleen in tumor bearing mice. Arch. Geschwulstforsch. 43, 1–7 (1974)
Klenshoj, N. C., Feldstein, M., Sprague, A. L.: The spectrophotometric determination of carbon monoxide. J. biol. Chem. 183, 297–303 (1950)
Koob, G. F., Annau, Z., Rubin, R. J., Montgomery, M. R.: Effect of hypoxic hypoxia and carbon monoxide on food intake, water intake, and body weight in two strains of rats. Life Sci. 14, 1511–1520 (1974)
Lowe, T. E., Bate, E. W.: The diameter of cardiac muscle fibres: A study of the diameter of muscle fibres in the left ventricle in normal hearts and in the left ventricular enlargement of simple hypertension. Med. J. Aust. 1, 467–469 (1948a)
Lowe, T. E., Bate, E. W.: Hyperplasia of cardiac muscle fibres. Med. J. Aust. 1, 618–620 (1948b)
Martinez Seeber, A., Labal, S. E., Catanzaro, O. L., Pola, J. L., Taquini, A. C., Jr.: The cardiac presso-receptors and the heart enlargement. Arch. int. Physiol. Biochim. 82, 873–880 (1974)
Otis, A. B.: The physiology of carbon monoxide poisoning and evidence for acclimatization. Ann. N.Y. Acad. Sci. 174, 242–245 (1970)
Penney, D., Benjamin, M., Dunham, E.: Effect of carbon monoxide on cardiac weight as compared with altitude effects. J. appl. Physiol. 37, 80–84 (1974a)
Penney, D., Dunham, E., Benjamin, M.: Chronic carbon monoxide exposure: The course of hemoglobin, heart weight and lactate dehydrogenase isozyme changes. Toxicol. appl. Pharmac. 28, 493–497 (1974b)
Penney, D., Sakai, J., Cook, K.: Heart growth: Interacting effects of carbon monoxide and age. Growth 38, 321–328 (1974c)
Stewart, R. D., Peterson, J. E., Fisher, T. N., Hosko, M. J., Baretta, E. D., Dodd, H. C., Herrmann, A. A.: Experimental human exposure to high concentrations of carbon monoxide. Arch. environm. Hlth 26, 1–7 (1973)
Stohlman, F., Jr.: Observations on the physiology of erythropoietin and its role in the regulation of red cell production. Ann. N.Y. Acad. Sci. 77, 710–724 (1959)
Theodore, J., O'Donnell, R. D., Back, K. C.: Toxicological evaluation of carbon monoxide in humans and other mammalian species. J. occup. Med., 13, 242–255 (1971)
Thomsen, H. K., Kjeldsen, K.: Threshold limit for carbon monoxide-induced myocardial damage. Arch. environm. Hlth 29, 73–78 (1974)
Turek, Z., Grandtner, M., Kreuzer, F.: Cardiac hypertrophy, capillary and muscle fibre density, muscle fibre diameter, capillary radius and diffusion distance in the myocardium of growing rats adapted to a simulated altitude of 3,500 m. Pflügers Arch. ges. Physiol. 335, 19–28 (1972)
Utidjian, H. M. D.: The criteria for a recommended standard occupational exposure to carbon monoxide. I. Recommendations for a carbon monoxide standard. J. occup. Med. 15, 446–451 (1973)
Author information
Authors and Affiliations
Additional information
Visiting Professor. Part of work done while recipient of a grant from the Wellcome Trust, November, 1973 – November 1974
We are grateful to Dr. D. C. Nicholson for his advice and assistance with the determinations of carboxyhaemoglobin levels and the chemical analyses, Professor W. M. Davidson for the use of the facilities of the haematology laboratory, Dr. S. M. Mohamedally for performing the hydroxyproline determinations, and to Professor M. J. H. Smith and Dr. P. Hugh-Jones for the use of their calculators.
Rights and permissions
About this article
Cite this article
Żebro, T., Littleton, R.J. & Wright, E.A. Adaptation of mice to carbon monoxide and the effect of splenectomy. Virchows Arch. A Path. Anat. and Histol. 371, 35–51 (1976). https://doi.org/10.1007/BF00433713
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00433713