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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.

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.

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.

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.