Role of platelet activating factor in development of thrombocytopenia and neutropenia in dogs with endotoxemia.
OBJECTIVE
To determine the role of platelet activating factor (PAF) in lipopolysaccharide (LPS)-induced thrombocytopenia and neutropenia in dogs.


METHODS
42 dogs.


METHODS
Blood samples were obtained from dogs given LPS (40 microg/kg of body weight; n = 16), PAF (1 microg/kg; 6), PAF (5 microg/kg/h for 90 minutes; 4), or physiologic saline (0.9% NaCl) solution (0.1 ml/kg/h for 90 minutes; 3) IV to monitor changes in blood cell counts, using automated counters and blood smears stained with Giemsa. Blood samples were also obtained from dogs given LPS (40 microg/kg) that had (n = 5) or had not (6) been treated beforehand with TCV-309, a potent PAF antagonist. Concentration of PAF in blood was determined by use of 125I-radioimmunoassay in dogs given LPS at 1 mg/kg (n = 3) and 40 microg/kg (9).


RESULTS
Thrombocytopenia and neutropenia were found in all dogs except those given saline solution. The LPS-induced thrombocytopenia was significantly suppressed by prior treatment with TCV-309. The PAF concentrations increased markedly 1 hour after injection of 1 mg/kg of LPS and increased slightly but significantly 10 minutes after injection of 40 microg/kg of LPS.


CONCLUSIONS
PAF plays an important role in the development of LPS-induced thrombocytopenia and neutropenia in dogs. Control of PAF production, PAF-induced effects, or both may be important in the treatment of dogs with gram-negative bacterial infections and associated thrombocytopenia and neutropenia.
Laboratory of Internal Medicine II, School of Veterinary Medicine, Azabu University, Sagamihara City, Kanagawa, Japan.
R
R
Tsuchiya
K
K
Kyotani
M A
MA
Scott
K
K
Nishizono
Y
Y
Ashida
T
T
Mochizuki
S
S
Kitao
T
T
Yamada
K
K
Kobayashi
D000818:Animals; D001780:Blood Coagulation Tests / Q000662:veterinary; D004283:Dog Diseases / Q000209:etiology*; D004285:Dogs; D019446:Endotoxemia / Q000150:complications / Q000662:veterinary*; D005260:Female; D007546:Isoquinolines / Q000494:pharmacology; D007958:Leukocyte Count / Q000662:veterinary; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009503:Neutropenia / Q000209:etiology / Q000662:veterinary*; D010865:Pilot Projects; D010972:Platelet Activating Factor / Q000378:metabolism* / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010976:Platelet Count / Q000662:veterinary; D011726:Pyridinium Compounds / Q000494:pharmacology; D011863:Radioimmunoassay / Q000662:veterinary; D044005:Tetrahydroisoquinolines; D013921:Thrombocytopenia / Q000209:etiology / Q000662:veterinary*
D007546:Isoquinolines; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011726:Pyridinium Compounds; D044005:Tetrahydroisoquinolines; C067430:TCV 309