Effect of pentoxifylline, flunixin meglumine, and their combination on a model of endotoxemia in horses.
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.


METHODS
24 healthy horses, aged 2 to 15 years.


METHODS
4 groups (n = 6/group) received 30 ng of Escherichia coli O55:B5 endotoxin/kg of body weight, i.v., 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.
Baskett
A
A
Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602, USA.
Barton
M H
MH
Norton
N
N
Anders
B
B
Moore
J N
JN
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D003002:Clonixin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004338:Drug Combinations; D019446:Endotoxemia / Q000188:drug therapy / Q000503:physiopathology / Q000662:veterinary*; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000097:blood / Q000662:veterinary; D006439:Hemodynamics / Q000187:drug effects; D006734:Horse Diseases / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006736:Horses; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count / Q000187:drug effects / Q000662:veterinary; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C014558:flunixin meglumine; D010959:Tissue Plasminogen Activator; D010431:Pentoxifylline; D003002:Clonixin