Effect of oxygen on the antagonism of cyanide intoxication--cytochrome oxidase, in vivo.
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Biomedical subjects
Publications and source records attributed to G E Burrows.
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Attempts were made to evaluate the effects of pretreatment with air and oxygen either alone or in various combinations with sodium nitrite and/or sodium thiosulfate on the physiological disposition of 14C-labeled sodium cyanide in mice. The radioactive respiratory excretion was studied by radiorespirometry, and the effects of various combinations of cyanide antagonists were compared. Oxygen either alone or in combination with sodium thiosulfate significantly enhanced the respiratory excretion when compared with air. Sodium thiosulfate accelerated the initial rate, but not the total amount of radioactivity excreted. The cumulative recovery of radioactive gases was significantly greater with groups receiving oxygen either alone or with sodium thiosulfate. When sodium nitrite was employed as an antidote either alone or with sodium thiosulfate, no difference in the respiratory excretion was noted between air and oxygen. The use of the sodium nitrite-sodium thiosulfate combination either with air or oxygen resulted in a marked decrease in the initial rate as well as the total amount of respiratory radioactivity excreted. No significant differences between various experimental groups were noted in the total amount of urinary radioactivity excreted or the total body retention of radioactivity.
Grass hay produced in the Coeur d'Alene River Basin of northern Idaho was fed to a group of 4 ponies. The hay contained Pb in concentration of 423 +/- 82 mg/kg and Cd in concentration of 10.8 +/- 1.4 mg/kg, resulting in daily exposures of the ponies to approximately 7.4 mg of Pb/kg and 0.19 mg of Cd/kg/day. The results in this group of ponies were compared with those from a group fed noncontaminated grass hay and given a daily dose of 10 mg of Pb/kg of body weight, in the form of lead acetate. Clinical toxicologic signs, hematologic changes, and blood and tissue Pb concentrations were similar in the 2 groups. However, the severity of the disease process appeared to be greater in the ponies fed the Pb- and Cd-contaminated hay. This was shown clearly by the shorter interval between onset of clinical changes and death in the ponies fed contaminated hay. The possibility of multiple heavy metal effects is discussed. Clinical toxicologic signs observed include incoordination, labial paresis, pharyngeal paresis, CNS depression, anorexia, and body weight loss. Anemia or marginal anemia was common and was often accompanied by the appearance of nucleated RBC and Howell-Jolly bodies in peripheral blood. Neither the hematologic response nor the blood Pb concentrations were reflective of the severity of poisoning, although blood Pb concentrations were greater than 0.35 micrograms/ml once clinical signs of toxicity were observed. Liver, kidney, spleen, brain, and bone Pb concentrations and liver, kidney, and brain Cd concentrations were increased in both the ponies fed contaminated hay and the ponies given lead acetate.
In the spring of 1981, an informal survey of 22 US colleges of veterinary medicine was conducted. The purpose was to acquire information regarding the current commitment of such schools, each with an established and operational curriculum, for poisonous plant instruction. Aspects of commitment surveyed included number of instructional contact hours, pedagogical approach employed, and course content and topic emphasis. The results (summarized below) were presented at the American College of Veterinary Toxicologists "Symposium on Teaching Toxicology" held at the American Veterinary Medical Association annual meeting in St. Louis, Mo. in July of 1981.
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Endotoxins are non-protein fragments of the cell wall of Gram-negative bacteria. They must be absorbed into the circulation to produce disease and systemic effects are similar, regardless of bacterial source. Absorption of endotoxins occurs in obstructive bowel disease and may play a significant part in determining the severity of the disease. Many of the responses to experimentally administered endotoxin are identical to those of bowel diseases or the horse and include circulatory, haematological and metabolic alterations. Therapeutic approaches are indirect and include many drugs currently employed in equine practice. The agents are directed toward mediators of the disease rather than the endotoxins themselves and include fluids, corticosteroids, anti-inflammatory drugs, energy sources and vasoactive drugs. The rationale for use and dosages are discussed.
Phenylbutazone (PBZ), a classic anti-inflammatory and prostaglandin-synthesis inhibitor drug, was used to determine the role of prostaglandins and other mediators on the development and perpetuation of the response to intraperitoneal Escherichia coli endotoxin administration. The PBZ (15 mg/kg of body weight) was administered IV 30 minutes after endotoxin administration and was repeated later at 6 and 12 hours at a dose of 10 mg/kg. A variety of evaluation measurements (hematologic, blood glucose, pyruvate, lactate and fibrinogen, serum beta-glucuronidase, prothrombin time, blood gases, hepatic glycogen, plasma esterase, capillary refill time, and rectal temperature) were utilized. Marked alterations were noted for all evaluators following endotoxin administration except for blood fibrinogen, prothrombin time, and plasma esterase activity. The PBZ therapy blocked the hemoconcentration, hyperglycemia, increased blood lactate, decreased bicarbonate, decreased blood pH, pyrexia, and prolonged capillary refill time responses associated with endotoxin administration. Despite the significant blocking effects of PBZ on endotoxin responses, the eventual survival rate was unaffected in these experiments.
Various cyanide antidotes were evaluated by comparing the effects of delay in time of therapy following oral administration of sodium cyanide in sheep. Successful therapy of lethal doses of sodium cyanide could be accomplished with the more potent antidotes for up to 30 minutes following administration of sodium cyanide. Either 660 mg/kg sodium thiosulfate or 1 mg/kg p-aminopropriophenone were effective antidotes for moderate lethal doses (7.6 mg/kg) of sodium cyanide. The conventional low dosage nitrite/thiosulfate (6.7 mg/kg and 67 mg/kg) was much less effective. Larger doses (15.2 mg/kg) of sodium cyanide were effectively antagonized by either 660 mg/kg sodium thiosulfate alone or in combination with 1.5 mg/kg p-aminopropriophenone or 22 mg/kg sodium nitrite. At high cyanide dosage, p-aminopropriophenone alone was less effective than sodium thiosulfate alone. Sodium thiosulfate at high dosage appears to be the antidote of choice. This more closely satisfies the requirements of high efficacy and low toxicity for an antidote. Sodium nitrate or other antidotes may be used in conjunction with sodium thiosulfate, but their use is not necessary for high efficacy.
The response of the pony to increasing doses of Escherichia coli endotoxin was evaluated using intravenous and intraperitoneal administration models. Marked changes were seen in all parameters measured following endotoxin administration. Leukopenia (neutropenia, lymphopenia) and thrombocytopenia were not dose-dependent. Similarly, elevated plasma fibrinogen and altered glucose concentrations (hyperglycemia and hypoglycemia), pyrexia and increased lactate/pyruvate ratios were apparent at all endotoxin doses but were not dose related. The widely used packed cell volume and capillary refill time, we well as blood lactate and possibly serum beta-glucuronidase, were increased in a dose-related manner.
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Repeated exposure of ponies in Escherichia coli endotoxin resulted in attenuation of the packed cell volume, beta-glucuronidase, capillary refill time and neutrophil responses usually accompanying endotoxin administration. An overall decrease in severity of clinical response including reduced mortality was also apparent in ponies with repeated endotoxin exposure. Modification of the febrile response was not observed in any of the experimental groups.
Certain physiologic and hematologic data were determined in ponies given Escherichia coli endotoxin by three routes: single IV dose, single intraperitoneal (IP) dose, and multiple IP boluses. In all ponies, the reaction was characterized by weakness, depression, peripheral circulatory abnormalities, and pyrexia. The pyrexia was more severe and was sustained in the ponies given multiple IP bolus endotoxin. Changes in packed cell volume, peripheral blood neutrophil, lymphocyte, and thrombocyte counts, and blood glucose were noticed in the three groups. Blood lactate and beta-glucuronidase values were determined and increases occurred only in the two IP endotoxin administration groups. A fibrinogen increase was observed in only the multiple IP bolus group. Attempts were made to correlate the lactate and beta-glucuronidase values with the severity and prognosis of the endotoxemia response. In general, the single IV bolus and, to a lesser extent, the single IP bolus endotoxin produced abrupt but transient responses. The multiple IP bolus endotoxin administration produced a more gradual and sustained response, which was more closely comparable with a clinical gastrointestinal disease problem than the other routes of administration produced.