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Beneficial effects of UK 37248, a thromboxane synthetase inhibitor, in experimental endotoxic shock in the rat.
Author(s) -
Halushka PV,
Cook JA,
Wise WC
Publication year - 1983
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1983.tb02124.x
Subject(s) - medicine , radioimmunoassay , endocrinology , thromboxane b2 , prostaglandin , chemistry , alpha (finance) , thromboxanes , thromboxane , prostaglandins f , platelet , nursing , patient satisfaction , construct validity
1 The effects of pretreatment with the thromboxane synthetase inhibitor UK 37248 (dazoxiben) administered 30 min before intravenous endotoxin (S. enteriditis) in the rat was investigated 2 Plasma prostaglandins and thromboxanes were determined via radioimmunoassay. Endotoxaemia was associated with significant elevations above control values (less than 200 pg/ml) in plasma thromboxane B2 (TXB2), prostaglandin E (PGE) and 6‐ keto‐prostaglandin F1 alpha (6‐keto‐PGF1 alpha). Within 30 min after endotoxin administration plasma immunoreactive (i) iTXB2 was 875 +/‐ 90 pg/ml (n = 9), iPGE was 1670 +/‐ 271 (n = 9) and i6‐keto‐PGF1 alpha was 1191 +/‐ 209 pg/ml (n = 10). By 4 h plasma iTXB2 was 1743 +/‐ 328 pg/ml (n = 5), iPGE was 2589 +/‐ 494 pg/ml (n = 9) and i6‐keto‐PGF1 alpha was 4251 +/‐ 984 pg/ml (n = 10). UK 37248 pretreatment resulted in a significant (P less than 0.001) decrease in plasma iTXB2 at 30 min and 4 h to 193 +/‐ 28 pg/ml (n = 5) and 421 +/‐ 57 pg/ml (n = 5), respectively. Unexpectedly UK 37248 also significantly decreased plasma i6‐keto PGF1 alpha at 30 min and 4 h to 360 +/‐ 75 pg/ml (n = 10) (P less than 0.005) and 1920 +/‐ 513 pg/ml (n = 10) (P less than 0.05), respectively, iPGE plasma levels were not significantly changed in the UK 37248‐pretreated rats 30 min (2210 +/‐ 370 pg/ml (n = 9) or 4 h 3529 +/‐ 1093 pg/ml (n = 13) after endotoxin compared to the vehicle‐treated rats. 3 UK 37248 significantly (P less than 0.05) reduced the endotoxin mortality rate at 24 h from 69% (n = 13) to 30% (n = 13), UK 37248 also reduced splanchnic infarction from 90% (n = 20) to 6% (n = 16). 4 UK 37248 significantly improved the endotoxin‐induced thrombocytopaenia, disseminated intravascular coagulation, hypoglycaemia and lysosomal labilization. 5 We conclude that UK 37248 provides significant beneficial effects in experimental endotoxic shock in the rat.