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SUMMARY

Objective

To evaluate the effect of pentoxifylline on response of horses to in vivo challenge exposure with endotoxin.

Animals

24 healthy horses in 3 treatment groups: pentoxifylline, endotoxin, or endotoxin and pentoxifylline.

Procedure

Horses of the pentoxifylline group were given a bolus of pentoxifylline (7.5 mg/kg of body weight, IV), followed by an infusion (3 mg/kg/h) over 3 hours, and those of the endotoxin group were given 20 ng of endotoxin/kg IV over 30 minutes. Those of the combination group were given both of the aforementioned compounds; pentoxifylline was administered immediately after endotoxin. Clinical (rectal temperature, heart and respiratory rates, blood pressure) and hematologic (WBC count; whole blood recalcification time; plasma fibrinogen, thromboxane B2, and 6-keto-prostaglandin F, concentrations; plasma plasminogen activator inhibitor activity; and serum tumor necrosis factor and interleukin 6 activities) variables were evaluated over 24 hours.

Results

Compared with baseline values, there were no significant changes in any variable over time in the horses receiving only pentoxifylline, with the exception of a significant increase in WBC count. Rectal temperature, heart rate, mean blood pressure, WBC count, whole blood recalcification time, fibrinogen concentration, plasminogen activator inhibitor activity, tumor necrosis factor and interleukin 6 activities, and plasma thromboxane B2 concentration changed significantly over time in horses of the endotoxin and endotoxin-pentoxifylline combination groups. Respiratory rate and plasma 6-keto-prostaglandin F concentration changed significantly over time only in horses of the endotoxin group. Compared with values for the endotoxin group, rectal temperature and respiratory rate were significantly lower, and whole blood recalcification time was longer for the endotoxin/pentoxifylline group.

Conclusion

Beneficial effects of pentoxifylline are limited when it is administered IV to horses after in vivo challenge exposure with endotoxin. (Am J Vet Res 1997;58:1300–1307)

Free access
in American Journal of Veterinary Research

SUMMARY

Objective

To compare effects of a single dose of pentoxifylline (PTX), flunixin meglumine (FM), and their combination (FM/PTX) in a model of equine endotoxemia.

Animals

24 healthy horses, aged 2 to 15 years.

Procedure

4 groups (n = 6/group) received 30 ng of Escherichia coli O55:B5 endotoxin/kg of body weight, IV, over 30 minutes, and 1 of the following preparations 15 minutes before and 8 hours after endotoxin infusion: FM, 1.1 mg/kg; PTX, 8 mg/kg; FM/PTX, 1.1 mg of FM and 8 mg of PTX/kg; and saline solution bolus (ENDO). Clinical and hematologic variables were measured over 24 hours.

Results

Compared with ENDO, FM given before endotoxin significantly reduced TxB2, and 6-keto-PGF1 concentrations, pulse, rectal temperature, and attitude score. Pentoxifylline given before endotoxin resulted in significantly higher 6-keto-PGF1 concentration at 1.5 hours and significantly lower PAI-1 activity at 12 hours. Tumor necrosis factor and IL-6 activities in horses given PTX alone were not significantly different from values in those given the saline bolus. FM/PTX induced effects similar to those of FM alone on endotoxin-induced changes in temperature and TxB2 concentration, and 6-keto-PGF1 concentration was significantly lower than that in horses of the ENDO group at 1 hour. In horses of the FM group, 6-keto-PGF1 concentration was significantly lower than that in horses of the ENDO group, from 0.5 hour to 2 hours. Horses of the FM and FM/PTX groups had significantly higher IL-6 activity at 1.5 and 2 hours than did horses of the PTX and ENDO groups; those of the FM and FM/PTX groups had significantly lower WBC count than did those of the PTX and ENDO groups.

Conclusions

FM/PTX may help offset deleterious hemodynamic effects of endotoxin more effectively than does either FM or PTX alone. (Am J Vet Res 1997;58:1291–1299)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To test efficacy of murine monoclonal, rabbit polyclonal recombinant equine or human tumor necrosis factor-α (rETNF or rHTNF, respectively) antibodies to inhibit native equine tumor necrosis factor (TNF) activity.

Animals

8 and 18 healthy adult horses for parts 1 and 2 of the study, respectively.

Procedures

In part 1, supernates from endotoxin-activated peritoneal macrophages were incubated with various dilutions of each rETNF antibody and subsequently tested for TNF activity. Serum was also obtained from a horse 1 hour after infusion with 20 ng of endotoxin/kg of body weight and was incubated with various dilutions of rabbit polyclonal rHTNF antibody. In part 2, 20 ng of endotoxin/kg was infused in horses during a 30-minute period. Fifteen minutes after the endotoxin infusion was initiated, 1 of 3 preparations was infused: 0.1 mg of rabbit polyclonal rHTNF antibody/kg, 0.1 mg of human IgG/kg, or 500 ml of 5% dextrose. Clinical and hematologic data were collected for 24 hours.

Results

Compared with the monoclonal antibody, the rabbit polyclonal rETNF antibody was more effective in inhibiting TNF activity. The 50% effective doses of the murine monoclonal rETNF, rabbit polyclonal rETNF, and rabbit rHTNF antibodies were 1.8, 0.8, and 0.6 μg of antibody/ml, respectively. In part 2, endotoxin infusion resulted in significant alternations in all variables; however, differences among treatment groups were not significant.

Conclusions and Clinical Relevance

Although murine monoclonal and rabbit polyclonal rETNF or rHTNF antibodies are capable of inhibiting native equine TNF activity in vitro, when given after initiation of endotoxemia, administration of 0.1 mg of rabbit polyclonal rHTNF/kg does not alter the response to infusion of endotoxin. (Am J Vet Res 1998;59:792-797)

Free access
in American Journal of Veterinary Research