The release of prostanoids during the acute pulmonary response to E. coli endotoxin in anaesthetized cats

Abstract

1 The administration of E. coli endotoxin (2 mg/kg i.v.) to anaesthetized cats results in a characteristic acute pulmonary response. This consists of increases in pulmonary artery pressure and airways resistance and a reduction in lung compliance.2 Plasma concentrations of prostaglandin E2 (PGE2), PGF2a, thromboxane B2 and 6-keto PGF1, were measured by radioimmunoassay in aortic and pulmonary arterial blood samples before, during and after the acute pulmonary response to endotoxin. 3 Endotoxin administration resulted in the rapid release of PGF20, and thromboxane B2 from the lungs. The time course of this release was parallel to that of the pulmonary hypertensive and airways responses to endotoxin. PGE2 and 6-keto PGF1, were released more gradually and with greater variations between individual animals. 4 During the delayed shock phase (2 h after endotoxin) the concentrations of PGE2, PGF2, and 6-keto PGF1, were once again elevated in both the aorta and pulmonary artery. Thromboxane B2 concentrations were not increased at this time.5 These results suggest that PGF2. and thromboxane A2 may be mediators of the acute pulmonary responses to endotoxin.

Prostaglandins and thromboxane in the delayed phase of shock induced by Serratia marcescens endotoxin

“…These effects are very similar to those described in this species following the administration of endotoxin derived from E. coli (Parratt, 1973 (Anderson et al, 1975;Herman & Vane, 1976;Fletcher et al, 1976). Increased concentrations of TXB2 have been observed in the rat after Salmonella enteritidis endotoxin and in the cat during the early phase of E. coli endotoxaemia (Parratt et al, 1982;Coker et al, 1983).…”

Effect of dazoxiben, a specific inhibitor of thromboxane synthetase, on acute pulmonary responses to E. coli endotoxin in anaesthetized cats.

“…The effects of exogenous PGF2a in this particular model have already been described and consist of pulmonary hypertension, increased airways resistance and reduced lung compliance. These are precisely the effects observed with endotoxin itselfand there is good evidence that PGF2a is produced by the lung early in shock and indeed that arterial levels of this prostanoid relate well to the alterations in pulmonary function (Coker etal., 1981;1983). Much less is known about the pulmonary effects of TXA2 in this model although unpublished studies in this laboratory with the thromboxane-like endoperoxide analogue U-46619 demonstrate that this substance also mimics the acute pulmonary effects of endotoxin.…”

“…These are PGF2a and the highly unstable thromboxane (TXA2) (Coker et al, 1981). The effects of exogenous PGF2a in this particular model have already been described and consist of pulmonary hypertension, increased airways resistance and reduced lung compliance.…”

“…However, the question as to which particular arachidonic acid derivative is largely responsible is unanswered. We have recently demonstrated (Coker et al, 1981) that PGF2a and thromboxane (which both elicit changes in pulmonary function similar to those of endotoxin) are released from the lungs in the very early stages of E. coli endotoxin shock and, furthermore, that arterial and mixed venous levels of both substances are elevated in septic shock patients with severe pulmonary complications . The availability of dazoxiben (UK 37248-01), a selective inhibitor of thromboxane synthesis should allow us to determine whether or not thromboxane is largely responsible for these adverse pulmonary changes.…”

Modification by steroids of pulmonary oedema and prostaglandin E2 pharmacokinetics induced by endotoxin in rats

“…Increased levels of prostaglandins in pulmonary venous blood after endotoxin in vivo have been demonstrated (Anderson et al, 1975;Fletcher & Ramwell, 1977;Coker et al, 1983) and these results have been interpreted as increased pulmonary synthesis of prostaglandins. They could equally be due to decreased inactivation of prostaglandins.…”