Ray L. Ball, DVM
Carbon monoxide (CO) is the leading cause of poisonings in the United States and causes 3500–4000 deaths per year.10 Its pathology is related to tissue hypoxia and cerebral edema. The mechanism of this hypoxia is due to the high affinity CO has to bind with hemoglobin molecules. This affinity can be from 240–300 times stronger than the affinity for oxygen, depending on the species. The national ambient air quality standard (NAAQS) has recognized that in most individuals, CO in low levels is non-toxic, and has established exposure levels for people that permit up to 9 ppm over 8 hours or 25 ppm over 1 hour as levels that will result in carboxyhemoglobin (COHb) of less than 2%.10 Subacute levels (less than 20% COHb) may cause such symptoms as inattentiveness and gastroenteritis. Acute toxicity can be seen at levels around 20% COHb. Clinical signs include headache, nausea, chest pain, and irritability. At levels approaching 40–60%, stupor, coma, and death are the possible outcomes. Chronic toxicity can cause such conditions as polycythemia, neuropsychiatric disorders, cardiac toxicity, and fetal effects. In veterinary medicine, the most common presentation of CO toxicity is seen in farrowing houses, with stillbirths and perinatal deaths being significant. Carbon monoxide has widespread effects on the mammalian fetus. These include teratogenicity, neurologic disorders, reduced birthweights, and an increased incidence of stillbirths.7 These effects are the result of two mechanisms: the direct effect of CO on the fetus and the hypoxic stress placed on the fetus prior to CO diffusion across the placenta. Experimental evidence in domestic animals has shown that a level of 9% COHb in the maternal circulation will effectively reduce the fetal oxygen blood content by 21%, equivalent to a 41% loss of hemoglobin or blood flow.6
The 1995–1996 AZA Annual Report on Conservation and Science reported that over 30% of newborn elephants are either stillborn or die within the first 30 days of life.3,4 It is known that elephant blood has the highest affinity for oxygen of any terrestrial mammal.1,2 Elephant hemoglobin has several amino acid substitutions that enhance oxygen binding, which enhance CO binding as well.5,8 Elephant myoglobin has also been demonstrated to have approximately six times greater affinity for CO than human myoglobin.9 Many elephants spend an extended amount of time indoors during the winter months in North America and Europe. While ambient levels of CO may be in the range acceptable for people, they may provide a source of exposure to more sensitive hemoglobin for months at a time. If these subacute levels (∼10%) are found consistently in confined elephants, it appears possible that any fetus present may be undergoing some level of hypoxic stress. It may even be possible that fetuses are lost before pregnancy was detected. This could play a role in defining irregular estrous cycles. A lot of questions remain regarding CO in elephants: what is the half-life of bound CO to maternal hemoglobin; what do 2,3-bisphosphoglycerate (2,3-BPG) levels do with elevated COHb; could CO have a role as a chemical messenger similar to nitrous oxide, and can it have a role in uterine leiomyomas? It is recommended that all elephant-holding facilities examine their heating equipment and consider this especially in their efforts to breed elephants.
1. Bartels, H., P. Hilpert, K. Barbey, K. Betke, K. Riegel, E.M. Lang, and J. Metcalfe. 1963. Respiratory functions of blood of the yak, llama, camel, Dybowski deer, and African elephant. Am. J. Physiol. 205(2): 331–336.
2. Dhindsa, D.S., C.J. Sedgwick, and J. Metca. 1972. Comparative studies of the respiratory functions of mammalian blood. VIII. Asian elephant (Elephas maximus) and African elephant (Loxodonta africana africana). Resp. Physiol. 14: 332–342.
3. Keele, M., and D. Olson. 1995–1996. African elephant (Loxodonta africana). AZA Annual Report on Conservation and Science. Pp. 76–77.
4. Keele, M. 1995–1996. Asian elephant (Elephas maximus). AZA Annual Report on Conservation and Science. Pp. 80–81.
5. Kerr, Ellen A., and Nai-Teng Yu. 1985. Resonance Raman studies of CO and O2 binding to elephant myoglobin (Distal His (E7) Gln). J. Biol. Chemistry. 260(14): 8360–8365.
6. Longo, L.D. 1976. Carbon monoxide: effects on oxygenation of the fetus in utero. Science. 19: 523–525.
7. Longo, L.D., and E.P. Hill. 1977. Carbon monoxide uptake and elimination in fetal and maternal sheep. Am. J. Physiol. 232: 324–330.
8. Mizukami, H., Bartnicki, D.E., and A.F. Romero-Herrera. 1983. Interaction of ligands with the distal glutamine in elephant myoglobin. J. Biol. Chem. 258(3): 1599–1602.
9. Stephanos, J.J., and A.W. Addison. 1990. Spectroscopic and kinetic aspects of Elephas maximus hemoglobin. Eur. J. Biochem. 189: 185–191.
10. Vreman, H.J., J.J. Mahoney, and D.K. Stevenson. 1995. Carbon monoxide and carboxyhemoglobin. Adv Pediatr. 42: 303–334.