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Abstract

Objective—To determine and compare substrate specificity and kinetic rate constants of feline and canine alcohol dehydrogenase (ADH) with ethanol (EtOH) and ethylene glycol (EG) as substrates in vitro, with and without fomepizole.

Sample Population—Livers from 3 dogs and 3 cats.

Procedure—Canine and feline ADH activity, in cytosolic fractions of homogenized liver, was determined by use of various concentrations of nicotinamide adenine dinucleotide (NAD), EtOH, or EG as substrates. Initial reaction velocities were calculated, and kinetic inhibition rate constants (Ki) for fomepizole were determined.

Results—Substrate specificity of canine and feline ADH for EtOH or EG was not significantly different. A 2-fold difference was detected in the maximal velocity of canine, compared with feline, ADH, using either substrate. Fomepizole Ki in feline hepatic homogenates was significantly greater than Ki in canine hepatic homogenates when either EtOH or EG was used as substrate (10- and 30-fold, respectively). A 6-fold increase in the concentration of fomepizole was required to achieve ADH inhibition, with feline homogenates equivalent to those of canine homogenates.

Conclusions and Clinical Relevance—Feline ADH has lower enzymatic capacity for turnover or is less concentrated in liver than canine ADH with regard to EtOH and EG catalysis. Canine ADH was more effectively inhibited by fomepizole than feline ADH. Results suggest that higher dosages of fomepizole may be more effective to treat cats with EG intoxication than dosages reported to treat dogs. (Am J Vet Res 2000;61:450–455)

Full access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association

Summary

The efficacy of 4-methylpyrazole (4-mp) and ethanol as treatment for ethylene glycol (eg) intoxication in cats was compared. Twenty-two cats were assigned at random to 6 experimental groups. Cats of 1 experimental group were given only 4-mp; those of another experimental group were given only eg. Cats of 3 experimental groups were intoxicated with eg and given 4-mp at 0 hour or 2 or 3 hours after eg ingestion, and those of 1 experimental group were given eg and treated with ethanol 3 hours after eg ingestion. Physical, biochemical, hematologic, blood gas, serum and urine eg concentrations, and urinalysis findings were evaluated at 0, 1, 3, 6, 9, 12, 24, 48, and 72 hours, 1 week, and 2 weeks after eg ingestion or 4-mp treatment in cats of the 4-mp only group. The half-life of eg and percentage of ingested eg excreted unchanged were determined for each group.

4-Methylpyrazole treatment at 0 hour was most effective at preventing metabolism of eg. 4-Methylpyrazole was not effective in preventing development of renal failure when given 2 or 3 hours after eg ingestion. Ethanol given 3 hours after eg ingestion was successful in preventing development of renal dysfunction in 2 of the 6 cats treated 3 hours after eg ingestion. Of the remaining 4 cats treated with ethanol, 2 developed transient renal dysfunction and 2 developed acute oliguric renal failure and were euthanatized.

4-Methylpyrazol given 2 or 3 hours after eg ingestion was less effective in preventing eg metabolism than was ethanol given 3 hours after eg ingestion. Therefore 4-mp, at the dose found to be effective in dogs, cannot be recommended as an alternative to ethanol for treatment of eg intoxication in cats.

Free access
in American Journal of Veterinary Research

Summary

4-Methylpyrazole (4-mp), an alcohol dehydrogenase inhibitor, was administered to dogs to treat ethylene glycol (eg) intoxication. Eleven dogs were given 10.6 g of eg/kg of body weight; 5 dogs were treated with 4-mp 5 hours after eg ingestion and 6 dogs were treated with 4-mp 8 hours after eg ingestion. 4-Methylpyrazole was administered iv as a 50-mg/dl solution in 50% polyethylene glycol: initial dose, 20 mg/kg; at 12 hours after initial dose, 15 mg/kg; at 24 hours after initial dose, 10 mg/kg; and at 30 hours after initial dose, 5 mg/kg. Physical, biochemical, hematologic, blood gas, serum and urine eg concentrations, and urinalysis findings were evaluated at 0, 1, 3, 6, 9, 12, 24, 48, 72 hours, and at 1 week and 2 weeks after eg ingestion.

Dogs of both groups developed clinicopathologic signs associated with eg intoxication, including cns depression, hyperosmolality, high anion gap metabolic acidosis, polydipsia, polyuria, calcium oxalate monohydrate and dihydrate crystalluria, and isosthenuria. Fractional excretion of sodium was increased in all dogs between 1 and 9 hours after eg ingestion, but remained increased beyond 24 hours only in the 2 dogs treated at 8 hours after eg ingestion that developed acute renal failure. All dogs treated 5 hours after eg ingestion recovered without morphologic, biochemical, or clinical evidence of renal impairment. Of the 6 dogs treated 8 hours after eg ingestion, 2 developed acute renal failure. One of the dogs treated 8 hours after eg ingestion remained isosthenuric for 2 months, but did not manifest any other signs of renal impairment. Of the dogs treated 8 hours after eg ingestion, 3 recovered without morphologic, biochemical, or clinical evidence of renal impairment. Serum half-life of eg was prolonged in the dogs treated 8 hours after eg ingestion. Percentage of eg excreted unchanged was 84 ± 2% in the dogs treated 5 hours after eg ingestion, and was 40 ± 10% in the dogs treated 8 hours after eg ingestion. 4-Methylpyrazole was effective in preventing renal failure in all dogs given 10.6 g of eg/kg when treatment was initiated by 5 hours after eg ingestion, and in 4 of 6 dogs when treatment was initiated by 8 hours after eg ingestion.

Free access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association
in Journal of the American Veterinary Medical Association

SUMMARY

Platelet aggregation and adenosine triphosphate (atp) secretion in response to arachidonic acid (10 μM) or collagen (5 μg/ml) were compared in healthy, adult female Beagles treated with low-dosage aspirin (3.5 mg/kg of body weight, po, q 12 h for 7 treatments) or with CGS 12970, a specific thromboxane synthetase inhibitor (10 mg/kg, po, q 8 h for 10 treatments). Platelet aggregation was assessed in whole blood by use of an electrical impedance method. Baseline values obtained prior to treatment served as controls. Addition of arachidonic acid to blood from nontreated dogs resulted in significantly (P < 0.001) increased impedance, but had no effect in blood from dogs treated with either aspirin or CGS 12970. Treatment with CGS 12970 or aspirin significantly (P < 0.001) decreased platelet atp secretion in response to arachidonic acid, compared with baseline values; however atp secretion in aspirin-treated dogs was significantly (P < 0.01) less than atp secretion in CGS 12970-treated dogs. Differences in platelet aggregation were not observed between control dogs and aspirin- or CGS 12970-treated dogs in response to collagen as an aggregant, however, collagen-induced platelet atp secretion was significantly (P < 0.001) decreased in dogs treated with aspirin, compared with control values and values from dogs treated with CGS 12970. In dogs treated orally with 0.1, 0.2, 1.0, or 10 mg of CGS 12970/kg, dose-dependent inhibition of arachidonic acid-induced platelet aggregation was observed, with impedance changes not observed at the 10-mg/kg dosage and normal platelet aggregation associated with the 0.1-mg/kg dosage. After a single orally administered dosage of 10 mg of CGS 12970/kg, platelet aggregation was maximally inhibited at 1 hour, remained negligible through 12 hours, and returned to normal by 96 hours. Platelet numbers were not affected by treatment with CGS 12970. These results indicate that similar to low-dose aspirin administration, treatment with CGS 12970 decreases arachidonic acid-induced, but not collagen-induced, whole blood platelet aggregation in dogs. Low-dose aspirin administration, however, was more effective than CGS 12970 treatment in reducing arachidonic acid- and collagen-induced platelet atp secretion.

Free access
in American Journal of Veterinary Research

Objective—

To evaluate safety and efficacy of 4-methylpyrazole (4-MP) treatment in dogs and to determine clinical signs and outcome of, and clinicopathologic abnormalities in, dogs treated in early or late stages of ethylene glycol (EG) intoxication.

Design—

Retrospective study.

Animals—

107 dogs.

Procedure—

For dogs treated with 4-MP, 1 of 2 dosage regimens was usually used: 20 mg/kg of body weight, IV, initially, 15 mg/kg 17 hours later, and 5 mg/kg 25 and 36 hours after the initial dose, or 20 mg/kg, IV, initially, 15 mg/kg 12 and 24 hours later, and 5 mg/kg 36 hours after the initial dose.

Results—

Neither adverse clinical signs nor clinicopathologic abnormalities were associated with the administration of 4-MP except in 1 dog, which developed tachypnea, gagging, excess salivation, and trembling after the second dose of 4-MP was given. Ethylene glycol intoxication was confirmed in 37 dogs. Of these, 21 were azotemic or became azotemic within 18 hours after admission, and only 1 of the 21 survived. All 16 dogs that did not become azotemic survived. Median time from EG ingestion to treatment with 4-MP was 5 hours (range, 2 to 8.5 hours) for dogs that were not azotemic at admission and 14.5 hours (range, 8.5 to 38 hours) for dogs that were azotemic at admission.

Clinical Implications—

4-MP was a safe and effective treatment for EG intoxication when it was given before sufficient quantities of EG had been metabolized to induce renal failure. Dogs treated within 8 hours of EG ingestion had a good prognosis. (J Am Vet Med Assoc 1996;209:1880–1883)

Free access
in Journal of the American Veterinary Medical Association

Summary

Approximately 10 of 100 young heifers that had recently delivered their first calf—members of a large Colorado dairy herd—had a syndrome of swollen teats and distal portions of the hind limbs, prefemoral lymphadenopathy, transient fever, rough coat, decreased milk production, and subsequent weight loss and reproductive inefficiency. Acute clinical signs of disease were associated with large numbers of Eperythrozoon wenyonii seen on blood smears, and resolution of signs correlated with reduction or disappearance of the parasite. Other known causes of peripheral edema could not be documented. The parasite was transmitted to 4 of 7 nonlactating dairy cows destined to be culled and a splenectomized calf via IV inoculation of blood from parasitemic heifers, but clinical signs of infection were not induced.

Free access
in Journal of the American Veterinary Medical Association