Beneficial effects of the peptidoleukotriene receptor antagonist, SK&F 104353, on the responses to experimental endotoxemia in the conscious rat.
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| Abstract |
The purpose of this study was to examine the effects of the peptidoleukotriene receptor antagonist, SK&F 104353, on the responses to endotoxin in conscious male Sprague-Dawley rats. Administration of Salmonella enteritidis endotoxin (30 mg/kg i.v.; LD90) resulted in a decrease in the number of circulating platelets, leukopenia, an increase in hematocrit, and 0% survival at 24 hr. Pretreatment with SK&F 104353 (1 mg/kg, i.v. bolus followed by 3 mg/kg/hr, i.v. infusion for 6 hr) 5 min before injection of endotoxin produced steady state plasma drug levels of 1.6 micrograms/ml in naive animals and levels of approximately 3.4 micrograms/ml in endotoxemic animals (P less than 0.05). SK&F 104353 significantly attenuated the endotoxin-induced thrombocytopenia (P less than 0.05) but had no effect on either the endotoxin-induced early leukopenia or late leukocytosis. Additionally, SK&F 104353 significantly reduced the endotoxin-induced hemoconcentration (P less than 0.05) and improved survival to 30% at 48 hr (P less than 0.05). A higher dose of SK&F 104353 (2 mg/kg, i.v. bolus followed by 10 mg/kg/hr, i.v. infusion for 6 hr) did not produce any further benefit. These data indicate clearly the pathophysiologic role of peptidoleukotrienes in endotoxemia and suggest SK&F 104353 could be useful for ameliorating some of the deleterious sequelae associated with this condition.
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| Authors | E F Smith 3rd, L B Kinter, M Jugus, M A Wasserman, R D Eckardt, J F Newton |
| Journal | Circulatory shock (Circ Shock) Vol. 25 Issue 1 Pg. 21-31 (May 1988) ISSN: 0092-6213 [Print] United States |
| PMID | 3042186 (Publication Type: Journal Article) |
| Chemical References |
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