Abstract
A case of poisoning with a Cotoneaster sp. is described in a llama (Lama glama). The clinical signs were dyspnea, with congested mucous membranes, chewing, recumbency, and opisthotonos. Several hours after ingestion of the plant, the llama died, despite treatment with sodium thiosulfate and nitrite. Necropsy revealed approximately 676 g of leaves and fruit of Cotoneaster in the first compartment of the stomach. The blood was light red and did not clot. Because Cotoneaster sp. contains low concentrations of cyanogenic glycosides, toxicosis occurs only following massive ingestion of plant material.
Cotoneaster species are often cultivated as ornamental small shrubs. Like Prunus laurocerasus and other plants from the Rosaceae family, Cotoneaster sp. can contain cyanogenic glycosides, but this genus has never been described before, to our knowledge, as a cause of poisoning in animals. 16 A 2.5-year-old llama (Lama glama L.) belonging to a circus was admitted to the Exotic Pets and Wildlife Clinic (National Veterinary School, Toulouse, France). Earlier that morning, the llama was tied up to a tree by its owner. The animal went unobserved and was discovered lying down 3 hr later. Upon admission to the clinic, the llama was unresponsive, stiff, and had opisthotonos. Physical examination revealed severe hypothermia with a rectal temperature of 31°C (resting temperature of adult llamas varies from 37.5–38.9°C). 2 The animal also had severe dyspnea with shallow and noisy breathing. The respiratory rate was 20 breaths/min (normal respiratory rate of llamas is 10–30 breaths/min). 2 The heart rate was 60 beats/min, suggesting bradycardia (normal resting heart rate of llamas is 60–90 beats/min). 2 The mucous membranes appeared congested and cyanotic. Tremors were observed in the limbs and the head. Although seizures were not observed, the animal exhibited chewing, recumbency, and opisthotonos. Blankets and a heating lamp were used in an attempt to raise the animal's body temperature. A catheter was placed in the left jugular vein, and the llama was given a lactated Ringer solution. Venous blood was light red and did not clot.
Because of the character of the blood and mucous membranes, cyanogenic glycoside poisoning was suspected. A mixture of 1 g of sodium nitrite and 5 g of sodium hydroxide thiosulfate in 40 ml of normal saline was prepared, and 20 ml of this mixture was administered intravenously. The animal exhibited less stiffness, and dyspnea had decreased in intensity. Ten ml of this solution also was administered 10 min and 40 min later. Following treatment, the llama breathed deeply and had fewer tremors but remained recumbent. Body temperature remained at 31°C, and the llama died 30 min later after an episode of polypnea, stiffness, and opisthotonos.
The body was refrigerated (4°C) overnight, and a necropsy was performed the following morning. The llama weighed 93 kg. The carcass was in poor body condition, with minimal body fat stores. The ophthalmic and oral mucous membranes were cyanotic. Clotted blood was not observed, and light red blood escaped when organs and tissues were incised. The muscles had a bright red color. The first compartment of the stomach (C1) contained approximately 10 liters of a wet and pasty mix with several leaves, fruit, and short fibers. The pH of the stomach was 6, which is a slightly acidic in llamas. 2 The third compartment (C3) contained 1 liter of a green mixture with some corn grains. The gastrointestinal mucosa was edematous. The remainder of the digestive tract was normal, with abundant digesta and feces. The kidneys were pale, with bilateral congestion of the corticomedullary junction. There was a severe pulmonary interstitial edema and diffuse congestion. In C1, 6,086 g of vegetal content were collected by hand. This material consisted of fruit (369 g) and leaves (307 g) of a plant that appeared to be Cotoneaster sp. Thus, approximately 676 g of plant material had been ingested by this 93-kg llama.
Identification of the plant was confirmed by light microscopy. Examination of the leaf surface disclosed calcium oxalate prismatic crystals in rows along the vascular strands of the leaves. Nonglandular trichomes were sharply bent from the base of the leaves. These 2 observations were characteristic of Cotoneaster sp. Several days later, the llama's owner submitted a sample of the shrub that subsequently was identified as Cotoneaster integerrimus Medicus.
The specimen submitted from the shrub, as well as the fruit and leaves collected from C1 at necropsy, were tested for the presence of hydrocyanic acid (Directive 71/250/CEE). The presence of hydrocyanic acid for both plant specimens was higher than the detection limit (1 mg/kg) but lower than the maximal quantification limit (10 mg/kg) of the diagnostic assay.
To the author's knowledge, this is the first report of Cotoneaster poisoning in animals. Previous investigators have identified cyanogenic glycosides in this plantspecies. 1,16 Prunasin occurs in the leaves and fruits, but amygdalin only occurs in fruits 10 of this plant. Seasonal variation in cyanogenic glycoside content exists, with greater quantities of these toxins occurring during rapid growth of the plant. Initial hydrolysis of the molecule releases the glycoside and a second hydrolytic step releases cyanhydric acid. 5 Cyanhydric acid binds hemoglobin and blocks the transport of oxygen. Cyanide also binds to cytochrome C oxidase and subsequently inhibits adenosine triphosphate production. 6 Other effects of cyanide include altered calcium metabolism with the release of neurotransmitters and altered catecholamine metabolism in the adrenal gland. 12,13
Clinical signs of cyanide poisoning often appear 15 min after ingestion of toxic plants and may include cyanosis, dyspnea, nervous and muscular abnormalities with tremors and convulsions, irregular heartbeat, loss of consciousness, and terminal respiratory. 12,14,15 Death generally occurs within 15–30 min after clinical signs develop. Necropsy findings include an aglycone odor, portions of the toxic plant in C1 of the stomach (or the rumen), bright red blood that fails to clot (not constantly found), hemorrhage, and bright red muscles. In humans, the clinical symptoms begin with headache, ataxia, and nausea, followed by dyspnea, palpitations, seizures, and unconsciousness. 13 If a large quantity of Cotoneaster sp. is ingested, death can occur within 10 min. In oral poisoning with plants containing amygdalin, the first symptoms may appear within 12 hr. 13
The toxicity of cyanogenic glycosides depends on the quantity ingested, the rate of ingestion, and other factors, including ruminal pH. 7 In llamas, the usual stomach pH is 6.4–7, except for the C3 compartment, which has a pH of 3 in the caudal portion. 2 The pH seen in C1 of the llama in the current case was more acidic and could have resulted in a relatively slow rate of hydrolysis of cyanogenic glycosides. Although the clinical course of disease was short (approximately 3 hr), the llama seemed to be relatively resistant to toxicosis because almost 700 g of leaves and fruit were ingested before signs of illness appeared. Furthermore, the llama died more than 4 hr after clinical signs began.
Plant poisoning was first suspected because the llama was tied to a tree, an alternate food source was not provided, and a Cotoneaster plant was within reach. Few cases of plant poisoning have been reported in llamas and most have involved plants from the Ericaceae family. 4,6,9 A presumptive diagnosis of cyanide poisoning was based upon the presence of dyspnea, hypothermia, tremors, loss of consciousness, cyanotic mucous membranes, and the presence of light red blood that failed to clot.
Cases of cyanogenic glycoside poisoning in herbivores are usually associated with ingestion of young leaves of Prunus laurocerasus or other Prunus spp. 12,14,15 Other cyanogenetic plants include arrowgrass (Triglochin L.) and chokeberry (Photinia Lindl). 3,4
Several treatments have been prescribed for cyanide poisoning in humans and animals. 8,13 Cobalt ethylenediamine tetra-acetic acid and/or hydroxocobalamin are more efficient treatments because they act immediately, but they were not available in the clinic. Supplemental oxygen administration also was not possible for this llama. Treatment with sodium thiosulfate and nitrite was tried because these agents were available. Thiosulfate transforms cyanide into thiocyanates that are then excreted by the kidney. 11 This treatment led to an immediate, but incomplete, clinical response. 8 Unfortunately, it was also impossible to measure methemoglobinemia, but the total dose of sodium thiosulfate and nitrite probably was not great enough to cause extensive methemoglobin formation because the blood remained bright red and was unable to clot even after death. Because ingested fruit and leaves were present, rumen (C1) lavage may have been beneficial; however, hypothermia and cyanosis prevented this treatment.
In conclusion, Cotoneaster sp. should be considered a toxic plant, even if it contains low concentrations of cyanogenetic glycosides. Although animals may avoid Cotoneaster sp if other sources of food are available, they will consume this plant if it is the only available food source.