Page 669 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

634 SECTION | IX Gases, Solvents and Other Industrial Toxicants

VetBooks.ir activity), preexisting cardiovascular or cerebrovascular with oxygen (Weaver, 2004). Cardiac myoglobin is par-
Myoglobin also has a higher affinity for CO compared
disease, cardiac insufficiency, increased affinity of hemo-
ticularly vulnerable to this effect, and the result is direct
globin (Hb) for CO (e.g., fetal Hb), and decrease blood
oxygen carrying capacity will reduce the tolerance to CO myocardial depression. CO myoglobin is described as
(Weaver, 2004). CO exposure is a noted cause of angina having a bright pink to red coloration. CO also binds to
in humans with preexisting cardiovascular disease. cytochrome oxidases in vitro although at lower affinity
Exposure of pregnant sows to CO levels of than oxygen. Thus, the in vivo relevance of this effect is
150 400 ppm for 48 96 h results in stillbirth rates of uncertain. However, such metabolic effects may have
6.7% 80.0% (Dominick and Carson, 1983). The risk of still- some relevance under conditions of tissue hypoxia.
birth increases significantly when COHb concentration is CO exposure produces substantial endovascular oxida-
greater than 23%. Notably, piglets that are born live in such tive stress (Weaver, 2004). CO triggers the release of oxy-
circumstances usually have hypoxic/ischemic leukoencepha- gen radicals from neutrophils and triggers nitric oxide
lopathy. There is evidence that preweaning pigs have some (NO) release from platelets with the subsequent formation
capacity to adapt to high air CO levels given that exposure to of peroxynitrate. CO also triggers brain neuronal apopto-
200 ppm of CO for the first 21 days of life has no adverse sis, particularly in the hippocampus, which contributes to
effect on any performance or behavioral characteristics in the common amnesic effects of the gas.
weanling pigs; however, exposure to 300 ppm in such
circumstances results in reduced growth and production per-
formance (Morris et al., 1985a, b). Perinatal exposure to Vulnerable Populations
250 ppm of CO resulting in a COHb level of approximately Vulnerable populations include any life stage in which
20% produced detrimental effects in neonatal pigs. fetal Hb is present, pregnant individuals, and individuals
with preexisting cardiovascular disease, anemia or any
Toxicokinetics and Toxicodynamics other factor resulting in reduced blood oxygen carrying
capacity (Weaver, 2004).
CO is one of the few diffusion-limited gases during respira-
tory absorption. Despite this, CO is rapidly absorbed through
the respiratory tract (Weaver, 2004). Approximately 85% of Clinical Presentation
absorbed CO binds to Hb with an affinity approximately
The most common clinical presentation is that the animal
200 300 times higher than that of oxygen, i.e., it has a high
is found either unconscious or dead following acute high-
blood:gas partition coefficient and a high degree of seques-
level CO exposure. Nonpigmented mucous membranes,
tration. The remainder binds to myoglobin in muscle and to
nails, and skin may have “cherry red” color. Humans with
blood proteins. Very small amounts are metabolized to car-
CO poisoning have been described as looking “pink-
bon dioxide, and subsequently exhaled. Free (unbound) CO
cheeked and healthy” (Weaver, 2004). Unfortunately,
is excreted primarily through the respiratory tract with a
cherry red coloration of the mucous membranes, skin, and
whole body half-life (t 1 /2 ) of 3 or 4 h in adult humans.
nails is not a reliable diagnostic sign, and very often
Treatment with 100% oxygen shortens the adult
“cherry red means dead.” When CO is used as a euthana-
human CO t 1 /2 to approximately 30 126 min, and treat-
sia agent in dogs, short periods of vocalization and agita-
ment with hyperbaric oxygen further shortens this to
tion can occur, even when the animal is apparently
about 23 min (Weaver, 2004). The human COHb t 1 /2 is
unconscious (Chalifoux and Dallaire, 1983).
much longer at 7 h.
With nonlethal exposures, any body system, organ, or
tissue can be affected (Weaver, 2004). Most commonly,
Pathophysiology clinical signs pertain to hypoxic central nervous system
The principal mode of action of CO is tissue hypoxia sec- (CNS) damage and may include apparent weakness,
ondary to reduced blood oxygen carrying capacity, i.e., it fatigue, depression, transient loss of consciousness, and
acts as a chemical asphyxiant (Weaver, 2004). Reduced seizure disorders. Cardiovascular signs and effects usually
blood oxygen carrying capacity occurs because of the pertain to the effects of reduced blood oxygen carrying
preferential binding of CO rather than oxygen to Hb. The capacity, tissue hypoxia, and direct effects on the myocar-
presence of COHb also results in a left shift of the oxy- dium and may include exercise intolerance, dyspnea, syn-
gen:Hb dissociation curve, further exacerbating tissue cope, and cardiac arrhythmias. Other noted effects
hypoxia. Organs and tissues with poorly developed anas- include retinal hemorrhage, hearing loss, rhabdomyolysis,
tomotic networks and high metabolic rates (e.g., the heart peripheral neuropathies, vomiting, and nausea. Permanent
and brain) are especially susceptible to CO-induced hyp- CNS injury, particularly to the hippocampus, caudate
oxia. Venous blood has a high level of COHb and is clas- nucleus, globus pallidus, and the substantia nigra (bilater-
sically described as being “cherry red” in color. ally), as well as the cerebellum, cerebral cortex, and